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AB - SP230EFFECT OF VITAMIN K2 SUPPLEMENTATION ON FUNCTIONAL VITAMIN K DEFICIENCY IN NON-DIALYZED PATIENTS WITH 3-5 STAGES OF CKD: A RANDOMIZED TRIAL Ilona Kurnatowska Ilona Kurnatowska 1 Medical University, to˙dż, Poland Piotr Grzelak Piotr Grzelak 1 Medical University, to˙dż, Poland Anna Masajtis-Zagajewska Anna Masajtis-Zagajewska 1 Medical University, to˙dż, Poland Magdalena Kaczmarska Magdalena Kaczmarska 1 Medical University, to˙dż, Poland Ludomir Stefańczyk Ludomir Stefańczyk 1 Medical University, to˙dż, Poland Cees Vermeer Cees Vermeer 2 Maastricht University, Maastricht, The Netherlands Katarzyna Maresz Katarzyna Maresz 3 International Science and Health Foundation, Cracow, Poland Michał Nowicki Michał Nowicki 1 Medical University, to˙dż, Poland Abstract Introduction and Aims: Patients with chronic kidney disaeses (CKD) suffer from accelered vascular calcification (VC) and vitamin K defficiency. The vitamin K-dependent matrix Gla protein (MGP) is one of the most powerful inhibitors of VC. This prospective randomized intervention study assessed the impact of vitamin K2 supplementation on levels of the inactive form of MGP desphospho-uncarboxylated MGP (dp-ucMGP) in non-dialyzed 3 -5 stages CKD patients. Methods: Common carotid intima media thickness (CCA-IMT), coronary artery calcification score (CACS), serum mineral parameters, matrix Gla protein (MGP), desphospho-uncarboxylated MGP (dp-ucMGP), osteocalcin (OC) were measured at baseline and after 270±12 days of supplementation of 90 μg of vitamin K2 (menaquinone-7, MK-7) with 10 μg cholecalciferol (K+D group) or 10 μg vitamin D (group D) in 42 non-dialyzed CKD patients. Results: During the treatment period no significant changes of eGFR in both groups were observed. The significantly lower increase of CCA-IMT during the intervention period was noticed in group K+D: from 0.95±0.2 mm at the beginning to 1.01±0.3 mm, p=0.003 at the end, and in D group: from 1.02±0.2 mm to 1.16±0.3 mm, p=0.003. The change of CACS was numerically less in vitamin K+D treated patients than in D group (ΔCACS: 63.1±108.5 A.u. vs 74.4±127.1, p=0.7; 16% and 15.8%, p=0.91, respectively). After nine months of MK-7 supplementation a significant decrease of dp-ucMGP was found 1077.1±507.7 pmol/L vs 961.5±506.7, p=0.02. This effect was not observed in D group: 793.9±400.3 pmol/L vs 820.7±565.2, p=0.7 respectively. The serum level of dp-ucMGP positively correlated with serum creatinine r=0.4, p=0,02, negatively with eGFR r=-0,5, p=0.003 at the beginning and r=0.4, p=0.03; r=-0.6, p=0.0001, respectively at the end of the study in both group. The positive correlation of dp-ucMGP and PTH level was noticed in all examined patients at the beginning and at the end of the study: r=0.4, p=0.04; r=0.4, p=0.01 respectively. Similar correlations were noticed between dp-ucMGP and OC: r=0.47, p=0.005; r=0.5; p=0.004 respectively. Any correlation between dp-ucMGP and estimated vascular changes was not find. Conclusions: The main determinant of dp-ucMGP level is the kidney function. Circulating level of dp-ucMGP may be a marker of vascular vitamin K status in CKD patients. The mechanisms by which vitamin K2 may exert the protective effect on progression of vessels damage are still uncertain, but may be connected with the impact of MK-7 on calcification’s regulators, including the impact on the MGP carboxylation process. SP231SYSTEMATIC REVIEW AND META-ANALYSIS OF SEVELAMER VERSUS CALCIUM-BASED BINDERS FOR THE TREATMENT OF HYPERPHOSPHATEMIA IN CHRONIC KIDNEY DISEASE Leena Patel Leena Patel 1 Cornerstone Research Group, Burlington, ON, Canada Lisa M Bernard Lisa M Bernard 1 Cornerstone Research Group, Burlington, ON, Canada Grahame J Elder Grahame J Elder 2 Westmead Hospital, Sydney, Australia 3 Garvan Institute of Medical Research, Sydney, Australia Abstract Introduction and Aims: A number of recently published studies have evaluated the efficacy and safety of the non-calcium-based binder (CBB) sevelamer versus CBBs. The aim of this study was to conduct an updated meta-analysis of sevelamer versus CBBs for the treatment of hyperphosphatemia in adult patients with CKD stages 3 to 5D. Methods: MEDLINE and the Cochrane Central Register of Controlled Trials were searched to identify RCTs or quasi-RCTs comparing sevelamer with CBBs. Patient-level outcomes assessed included all-cause mortality, cardiovascular (CV) events and mortality, hospitalization, adverse effects and quality of life (QOL). Intermediate outcomes included vascular calcification (VC) and changes to bone. Biochemical outcomes included values of serum phosphorus and calcium, hypercalcemia, the calcium-phosphorus (Ca × P) product, parathyroid hormone (PTH), alkaline phosphatase (ALP), bicarbonate, 1,25-dihydroxyvitamin D, fetuin A and lipids. We followed Cochrane guidelines for the conduct and reporting of this systematic review. Results: A total of 24 studies (4,330 participants) were included. The majority (87.5%) enrolled dialysis patients while 12.5% enrolled stage 3 to 5 CKD-ND patients. For patients treated with sevelamer vs. CBBs there were significant reductions in all-cause mortality (risk ratio [RR] 0.54, 95% confidence interval [CI] 0.32 to 0.93), serum cholesterol (mean difference [MD] -20.22 mg/dL, 95% CI -25.95 to -14.50), LDL-C (MD -21.64, 95% CI -27.88 to -15.41), hypercalcemia (RR 0.30, 95% CI 0.19 to 0.48), calcium (MD -0.43 mg/dL, 95% CI -0.64 to -0.22) and bicarbonate (MD -1.51 mEq/l, 95% CI -2.34 to -0.69). No significant between group differences were observed for CV mortality, serum phosphorus, ALP, PTH, the Ca × P product, HDL-C, 1,25-dihydroxyvitamin D, or the incidence of nausea/vomiting, constipation, diarrhea, or abdominal bloating. The incidence of combined gastrointestinal adverse events was higher with sevelamer vs. CBBs (RR 1.42, 95% CI 0.97 to 2.08). There were insufficient data for a formal meta-analysis of CV events, hospitalization, VC, bone outcomes, or QOL. A subgroup analysis of patients with CKD-5D revealed similar results to the primary analysis, except for all-cause mortality, which showed a non statistically significant 46% overall reduction (RR 0.54; 95% CI 0.29 to 1.01).Additional subgroup analyses were performed to investigate potential sources of heterogeneity between studies included in the analysis of all-cause mortality. In the analysis that included only studies where all-cause mortality was a pre-defined outcome, the risk of all-cause mortality for sevelamer vs. CBBs was no longer statistically significant (RR 0.53, 95% CI 0.26 to 1.09). The results for all-cause mortality were also sensitive to study duration, number of study participants, dialysis duration, and the presence of VC. Conclusions: For patients with CKD stages 3-5D, sevelamer vs. CBBs was associated with a 46% reduction in all-cause mortality that reached statistical significance. Sevelamer vs. CBBs was also associated with significant reductions in serum calcium, the risk of hypercalcemia, total and LDL-cholesterol and bicarbonate. A subgroup analysis that included only patients with CKD-5D showed a 46% overall reduction in mortality that did not reach statistical significance. Insufficient data were available to establish the comparative efficacy of sevelamer vs. CBBs for CV mortality, CV events, hospitalization, VC, bone outcomes, 1,25-dihydroxyvitamin D, or QOL. SP232A MULTI-METHOD QUALITY IMPROVEMENT INTERVENTION FOCUSING ON NEHROLOGISTS FAILS TO IMPROVE CLINICAL OUTCOMES IN CKD PATIENTS IN A CLUSTER-RANDOMIZED CLINICAL TRIAL (MAURO STUDY) Daniela Leonardis Daniela Leonardis 1 CNR-IFC, Reggio Calabria, Italy Francesca Mallamaci Francesca Mallamaci 1 CNR-IFC, Reggio Calabria, Italy Giovanni Tripepi Giovanni Tripepi 1 CNR-IFC, Reggio Calabria, Italy Graziella D'Arrigo Graziella D'Arrigo 1 CNR-IFC, Reggio Calabria, Italy Maurizio Postorino Maurizio Postorino 1 CNR-IFC, Reggio Calabria, Italy Giuseppe Enia Giuseppe Enia 1 CNR-IFC, Reggio Calabria, Italy Graziella Caridi Graziella Caridi 1 CNR-IFC, Reggio Calabria, Italy Francesco Marino Francesco Marino 1 CNR-IFC, Reggio Calabria, Italy Giovanna Parlongo Giovanna Parlongo 1 CNR-IFC, Reggio Calabria, Italy Carmine Zoccali Carmine Zoccali 1 CNR-IFC, Reggio Calabria, Italy - On Behalf Of Mauro Working Group - On Behalf Of Mauro Working Group Abstract Introduction and Aims: The Multiple interventions and AUdit to optimize Renal diseases cOntrol (MAURO) is a cluster randomized trial (NCT00566033) aimed at assessing whether a multi-method quality improvement intervention is more effective than a less intensive intervention (control arm) in order to improve clinical outcomes and adherence to a series of relevant quality indicators in CKD patients (J Nephrol. 2012;25:1081-90). The intensive intervention added periodic knowledge refreshing, telephone and e-mail contacts and audits to baseline education on CKD guidelines. Methods: Seven hundred and fifty-nine CKD patients (stages 2-5) were enrolled in 22 Nephrology Units Southern Italy. Eleven centers were randomized to the active arm (n = 410 patients) while the remaining 11 centers were randomized to the control arm (n= 349). Study outcomes included a composite end-point (eGFR reduction >30%, dialysis and transplantation, cardiovascular events and death). Additional study outcomes pertained the control of hypertension, proteinuria, dyslipidemia, anemia and CKD-BMD parameters. Results: During the follow-up (35 months), the incidence rate of the composite endpoint was almost identical (P = 0.49 ) in the two study arms (19 versus 18 events/100 person-years), and similar results were observed in separate analyses for renal events (P = 0.83), CV events (P = 0.44 ) and survival (P = 0.78). The control of hypertension, proteinuria, cholesterol and serum phosphate improved equally in the two study arms in longitudinal analyses (Mixed Linear Modelling) (Table). In both groups the progression rate of CKD was identical to that achieved in clinical trials testing ACE inhibitors in the Italian population (REIN and AIPRI studies, data not shown). Conclusions: A multimethod quality intervention aimed at enhancing nephrologists knowledge and applying reminders about patients out of clinical targets and clinical audits failed to show better outcomes as compared to a less intensive intervention (education on Guidelines at baseline). Results in this trial matched those of previous pharmacological clinical trials in the Italian population and in both study arms important risk factors for CKD progression like hypertension control and proteinuria improved over time indicating a beneficial effect of background education on Guidelines but little benefit of knowledge refreshing and clinical audits. Open in new tabDownload slide Open in new tabDownload slide SP233URINARY AND SEROLOGICAL MARKERS OF COLLAGEN DEGRADATION ARE ASSOCIATED WITH DISEASE SEVERITY AND INFLAMMATION IN IGA NEPHROPATHY PATIENTS Federica Genovese Federica Genovese 1 Nordic Bioscience, Herlev, Denmark Peter Boor Peter Boor 2 RWTH University of Aachen, Aachen, Germany Marios Papasotiriou Marios Papasotiriou 2 RWTH University of Aachen, Aachen, Germany Diana J Leeming Diana J Leeming 1 Nordic Bioscience, Herlev, Denmark Morten A Karsdal Morten A Karsdal 1 Nordic Bioscience, Herlev, Denmark Jürgen Floege Jürgen Floege 2 RWTH University of Aachen, Aachen, Germany Abstract Introduction and Aims: Matrix metalloproteinases (MMPs) mediate collagen degradation and thus generate neo-epitope fragments. Here we explore the use of such neo-epitopes (Protein Fingerprint markers) as diagnostic markers of chronic kidney disease (CKD) in a population of IgA nephropathy (IgAN) patients. Methods: In this single center retrospective study, the concentration of two Protein Fingerprint markers of collagen type I and type III degradation (sC1M and sC3M when assessed in serum and uC1M and uC3M when assessed in urine) was determined in samples from patients diagnosed with IgAN with different degrees of CKD, attending an outpatient clinic in Aachen. Only patients with a 2-year follow-up where included (n=33). The CKD stage was determined by the GFR calculated via the Cockroft-Gault formula. Serum C-reactive protein (CRP) was measured, and a value > 5 mg/l was regarded as indicating microinflammation. For comparison the two Protein Fingerprints were also measured in healthy subjects (n=12). Results: uC1M and uC3M levels decreased with the severity of CKD (table 1: statistical significance calculated with Kruskall-Wallis test and Dunn’s multiple comparison test as compared with CKD 1(#); **** p<0.0001, *** p<0.001, ** p<0.01, * p<0.05). After normalizing for urine creatinine, only uC3M remained significantly reduced. Serum C1M and sC3M levels were not related to CKD stage (all values were similar between the CKD stages and the healthy controls). Both serum markers could stratify patients to those with or without microinflammation (table 2: statistical significance calculated with Mann-Whitney test as compared with #; **** p<0.0001). The urinary markers did not correlate with the serum markers and none of the markers correlated with proteinuria. Conclusions: The results suggest that the degradation of collagen type III (determined by uC3M) decreased when IgAN progressed to more advanced CKD stages. This may indicate an impaired degradation of collagen following increased deposition and/or resistance to degradation following cross-linking of extracellular matrix proteins during the progression of kidney fibrosis. The decreased urinary values where not associated with reduced excretion since serum levels remained stable throughout the CKD stages. The serological markers of collagen degradation correlated with microinflammation, which is associated with an adverse prognosis in CKD patients. Mean uC1M and uC3M concentration before and after normalization for urine creatinine. . Mean value (ng/ml) . Mean value [Cre] (µg/mg creatinine) . uC1M Healthy 16.3 2.3 uC1M CKD1 27.5# 3.4# uC1M CKD2 20.2 4.4 uC1M CKD3 15.9**** 3.1 uC1M CKD4 14.2 3.2 uC3M Healthy 26.1 2.7 uC3M CKD1 20.5# 1.8# uC3M CKD2 7.9*** 1.5* uC3M CKD3 7.9**** 1.1**** uC3M CKD4 4.5** 0.8** . Mean value (ng/ml) . Mean value [Cre] (µg/mg creatinine) . uC1M Healthy 16.3 2.3 uC1M CKD1 27.5# 3.4# uC1M CKD2 20.2 4.4 uC1M CKD3 15.9**** 3.1 uC1M CKD4 14.2 3.2 uC3M Healthy 26.1 2.7 uC3M CKD1 20.5# 1.8# uC3M CKD2 7.9*** 1.5* uC3M CKD3 7.9**** 1.1**** uC3M CKD4 4.5** 0.8** Mean uC1M and uC3M concentration before and after normalization for urine creatinine. . Mean value (ng/ml) . Mean value [Cre] (µg/mg creatinine) . uC1M Healthy 16.3 2.3 uC1M CKD1 27.5# 3.4# uC1M CKD2 20.2 4.4 uC1M CKD3 15.9**** 3.1 uC1M CKD4 14.2 3.2 uC3M Healthy 26.1 2.7 uC3M CKD1 20.5# 1.8# uC3M CKD2 7.9*** 1.5* uC3M CKD3 7.9**** 1.1**** uC3M CKD4 4.5** 0.8** . Mean value (ng/ml) . Mean value [Cre] (µg/mg creatinine) . uC1M Healthy 16.3 2.3 uC1M CKD1 27.5# 3.4# uC1M CKD2 20.2 4.4 uC1M CKD3 15.9**** 3.1 uC1M CKD4 14.2 3.2 uC3M Healthy 26.1 2.7 uC3M CKD1 20.5# 1.8# uC3M CKD2 7.9*** 1.5* uC3M CKD3 7.9**** 1.1**** uC3M CKD4 4.5** 0.8** Mean sC1M and sC3M concentration in patients with different CRP levels. . Mean value (ng/ml) . sC1M Healthy 90.7 sC1M CRP<5 mg/l 73.6# sC1M CRP>5 mg/l 177.4**** sC3M Healthy 25.2 sC3M CRP<5 mg/l 26.9# sC3M CRP>5 mg/l 41.6**** . Mean value (ng/ml) . sC1M Healthy 90.7 sC1M CRP<5 mg/l 73.6# sC1M CRP>5 mg/l 177.4**** sC3M Healthy 25.2 sC3M CRP<5 mg/l 26.9# sC3M CRP>5 mg/l 41.6**** Mean sC1M and sC3M concentration in patients with different CRP levels. . Mean value (ng/ml) . sC1M Healthy 90.7 sC1M CRP<5 mg/l 73.6# sC1M CRP>5 mg/l 177.4**** sC3M Healthy 25.2 sC3M CRP<5 mg/l 26.9# sC3M CRP>5 mg/l 41.6**** . Mean value (ng/ml) . sC1M Healthy 90.7 sC1M CRP<5 mg/l 73.6# sC1M CRP>5 mg/l 177.4**** sC3M Healthy 25.2 sC3M CRP<5 mg/l 26.9# sC3M CRP>5 mg/l 41.6**** SP234ASSOCIATIONS BETWEEN A UMOD GENE VARIANT, UROMODULIN EXCRETION AND RENAL FUNCTION IN A LARGE CANADIAN SURVEY: THE CARTAGENE STUDY Catherine Delmas-Frenette Catherine Delmas-Frenette 1 Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada Stephan Troyanov Stephan Troyanov 2 Hôpital du Sacré-Coeur, Montréal, QC, Canada Philip Awadalla Philip Awadalla 3 Hôpital Ste-Justine, Montréal, QC, Canada Olivier Devuyst Olivier Devuyst 4 Zurich Center for Integrative Human Physiology, Zurich, Switzerland François Madore François Madore 2 Hôpital du Sacré-Coeur, Montréal, QC, Canada Abstract Introduction and Aims: Recent studies have suggested that uromodulin may play a role in chronic kidney disease. Genome-wide association studies have identified associations between single nucleotide polymorphisms near the UMOD gene and CKD. This study investigated the association between the UMOD variant rs4293393, the product of the gene, uromodulin, and GFR. Methods: A sample of 946 subjects from the CARTaGENE survey was genotyped for rs4293393. Urine uromodulin levels were measured using a validated ELISA method and expressed as a creatinine ratio. GFR was estimated using the CKD-EPI equation. Results: The population studied was 54±9 years old, composed of 51% of women and had a mean GFR (CKD-EPI) of 90±14 ml/min/1.73m2 and 68% presented the TT genotype. The CC/CT genotypes were associated with higher eGFR (CT/CC: 91±13 vs. TT: 89±14 ml/min/1.73m2, p=0.056) and lower urine uromodulin levels (CT/CC: 21, IQR 10-34 vs. TT: 27 (12-44) mg/g creatinine, p0.001), regardless of rs4294493 status. Using multivariate analysis, both the UMOD variant and uromodulin excretion were independent predictors of eGFR (rs4293393-C, p=0.029; urine uromodulin level, p<0.001) Conclusions: Uromodulin excretion decreases as the GFR declines. At the same time, the CC/CT variants of rs4293393 in the promoter region of UMOD are associated with a lower uromodulin excretion but a better renal function. Further studies are warranted to elucidate the mechanisms underlining these findings. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP235ABNORMAL URINARY EXCRETION OF NKCC2 AND AQP2 IN RESPONSE TO HYPERTONIC SALINE IN CHRONIC KIDNEY DISEASE. A CASE CONTROL STUDY Janni M Jensen Janni M Jensen 1 Regional Hospital Jutland West, Holstebro, Denmark 2 Aarhus University, Aarhus, Denmark Frank H Mose Frank H Mose 1 Regional Hospital Jutland West, Holstebro, Denmark Anna-Ewa O Kulik Anna-Ewa O Kulik 1 Regional Hospital Jutland West, Holstebro, Denmark Jesper N Bech Jesper N Bech 1 Regional Hospital Jutland West, Holstebro, Denmark Robert A Fenton Robert A Fenton 2 Aarhus University, Aarhus, Denmark Erling B Pedersen Erling B Pedersen 1 Regional Hospital Jutland West, Holstebro, Denmark 2 Aarhus University, Aarhus, Denmark Abstract Introduction and Aims: Renal handling of sodium and water is abnormal in chronic kidney disease (CKD). The aim of this study was to test the hypothesis that abnormal activity of the aquaporin2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contributes to this phenomenon. Methods: 23 patients with CKD and 24 healthy controls, at baseline and after 3% saline infusion, were compared. The following measurements were performed: urinary concentrations of AQP2 (u-AQP2), NKCC2 (u-NKCC2), ENaC (u-ENaCγ), glomerular filtration rate (GFR) estimated by 51Cr-EDTA clearance, free water clearance (CH2O), urinary output (UO), fractional excretion of sodium (FENa), plasma concentrations of vasopressin (pAVP), renin (PRC), Angiotensin II (pANG II), Aldosterone (pAldo) and body fluid volumes using bioimpedance spectroscopy technique. Results: At baseline, GFR was 34 ml/min in patients and 89 ml/ml in controls. There were no significant differences in u-AQP2, u-NKCC2 or u-ENaCγ, but FENa, p-Aldo and p-AVP, were higher in CKD patients than controls. In response to hypertonic saline, patients with CKD had an attenuated decrease in CH2O and UO. A greater increase in u-AQP2 was observed in patients compared to controls. Furthermore, u-NKCC2 increased in patients, whereas u-NKCC2 decreased in controls. U-ENaCγ did not differ. PRC, AngII and Aldo decreased in both groups all though levels were higher in CKD patients. Body fluid volumes did not significantly differ. Conclusions: The study documents an impaired ability to concentrate urine in patients with CKD. Infusion with 3% hypertonic saline increased u-AQP2 and u-NKCC2, suggesting an increased sodium reabsorption via the NKCC2 transporter and increased water reabsorption via the AQP2 water channels in patients with CKD. Despite high levels of pAVP and pAldo, the kidneys can only partly compensate and counteract acute volume expansion due to a defective tubular response. SP236VASCULAR CALCIFICATIONS IN CHRONIC KIDNEY DISEASE, DIALYSIS AND KIDNEY TRANSPLANT PATIENTS: MULTIDISCIPLINARY EVALUATION Silvia Lucisano Silvia Lucisano 1 Unit of Nephrology, University of Messina, Messina, Italy Antonino Villari Antonino Villari 2 University of Messina, Messina, Italy Filippo Benedetto Filippo Benedetto 3 Unit of Vascular Surgery, University of Messina, Messina, Italy Giuseppina Pettinato Giuseppina Pettinato 1 Unit of Nephrology, University of Messina, Messina, Italy Valeria Cernaro Valeria Cernaro 1 Unit of Nephrology, University of Messina, Messina, Italy Rosaria Lupica Rosaria Lupica 1 Unit of Nephrology, University of Messina, Messina, Italy Domenico Trimboli Domenico Trimboli 1 Unit of Nephrology, University of Messina, Messina, Italy Giuseppe Costantino Giuseppe Costantino 1 Unit of Nephrology, University of Messina, Messina, Italy Domenico Santoro Domenico Santoro 1 Unit of Nephrology, University of Messina, Messina, Italy Michele Buemi Michele Buemi 1 Unit of Nephrology, University of Messina, Messina, Italy Abstract Introduction and Aims: Vascular calcification is a prevalent pathology in patients with chronic kidney disease (CKD). These patients exhibit a hugely elevated risk of cardiovascular mortality compared with age-matched controls and develop accelerated medial as well as intimal calcification; this calcification rapidly progresses in patients on dialysis. The development of calcification in CKD patients is strongly linked to dysregulated mineral metabolism, endothelial dysfunction and oxidative stress. We studied localization, chemical composition and structure of vascular calcifications in these patients. Methods: The study was conducted on 40 patients with IV-V stage of CKD, 10 dialysis patients (HD), 10 Kidney transplant patients (Tx) and a control group. We first studied calcified plaques with computed tomography and ultrasonography. After we extracted the plaques, observed the structure under the electron microscope and studied the chemical composition of calcified part with the use of spectrophotometry (biological component was enzymatically degradated). (Fig. 1A) We also measured with immunohistochemistry the expression of sirtuin 1 and 4 in each plaque.(Fig. 1B) Finally we correlated the results obtained with indices of renal function and inflammation. Results: CKD, HD and Tx patients have a greater number and spread of plaques compared with controls (Figure 2A). The plaques are higher volume and the percentage of necrotic core and calcium is greater than fibrous tissue (p <0.0001)(Figure 2B). Different is also the chemical composition: calcium phosphate and apatite are more represented in CKD, HD and Tx, while in the controls whitlockite and calcium phosphate/apatite are represented in the same measure. Sirtuina1 and 4 are mainly expressed in the plaques of CKD patients (p <0.005 ), indicating greater hemodynamic stress (Figure 2C). Calcium, pH, blood urea nitrogen, creatinine and hsRCP are positively correlated with number and volume of calcified plaques (Table 1). Conclusions: CKD affects the number and composition of arterial plaques. The plaques of these patients are more unstable and at rupture risk. Important is the early control of hemodynamic and metabolic complications. Fig 1 Open in new tabDownload slide Fig 1 Open in new tabDownload slide Fig 2 Open in new tabDownload slide Fig 2 Open in new tabDownload slide Open in new tabDownload slide Open in new tabDownload slide SP237CHRONIC KIDNEY INJURY AND HYPERTENSION ASSOCIATE WITH INCREASED URINARY SUCCINATE LEVELS Claudia Carmone Claudia Carmone 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Joris H Robben Joris H Robben 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Juliette Hadchouel Juliette Hadchouel 2 INSERM U970, Paris Centre for Cardiovascular Research, Paris, France Gerard Rongen Gerard Rongen 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Jaap Deinum Jaap Deinum 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Gerjan J Navis Gerjan J Navis 3 University Medical Centre Groningen, Groningen, Netherlands Jack FM Wetzels Jack FM Wetzels 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Peter MT Deen Peter MT Deen 1 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands Abstract Introduction and Aims: Chronic Kidney Disease (CKD) is a common disease that affects about 10% of the general population and leads to a progressive loss of kidney function or cardiovascular diseases. Two fundamental characteristics of this pathology are the progressive reduction of Glomerular Filtration Rate (GFR) and an increase in the blood pressure, due to fluid overload and Renin Angiotensin Aldosterone System (RAAS) activation. The most common causes of CKD are diabetes and hypertension and it is also well known that independently of its cause, CKD is often associated to renal oxidative stress. More important in relation to CKD is that: in mice with Diabetes Mellitus type 1 (DM1), which give oxidative stress, activation of the SUCNR1 in the luminal membrane of Macula Densa cells by succinate is essential for renin release and development of hypertension. Given the correlation between CKD, hypertension, oxidative stress and SUCNR1, in this study we investigated the potential involvement of SUCNR1 in renal diseases. Methods: An enzymatic assay optimized for low-volume measurements was used to measure urinary succinate concentration. All the values obtained from the assay were corrected for urinary creatinine levels. P-values <0.05 were considered significant. Results: Urinary succinate levels were: 2.7 fold higher in CKD stage 2-4 patients than of healthy controls; 4.2 fold higher in hypertensive CKD patients versus controls; 1.4 fold higher in primary aldosteronism patients versus controls; 1.7 fold higher in a mouse model of Familial Hyperkalemic Hypertension (FHHt) with WNK1 mutations vs. wild-type littermates. In hypertensive CKD patients treated with ACE inhibitors, urinary succinate decreased 3.1 fold following use of Angiotensin receptor blockers (ARBs) and 2.7 fold when subjected to a low-sodium diet. In contrast, subjecting healthy individuals to a high/low sodium diet, or 1-5 days aldosterone infusion in adrenalectomized rats did not change urinary succinate levels. Conclusions: Renal succinate release is increased in all animal models and patients with affected renal function associated with chronic oxidative stress. With hypertensive CKD patients, urinary succinate levels correlated with the extent of sodium intake, hypertension and proteinuria. As urinary succinate activates SUCNR1, these data indicate to a role for SUCNR1 in activation of the intrarenal RAAS system and/or renal fibrosis as are commonly observed in these chronic renal disorders. SP238A DOUBLE-BLIND PLACEBO CONTROLLED RANDOMIZED TRIAL OF FERRIC CITRATE COORDINATION COMPLEX FOR THE TREATMENT OF IRON-DEFICIENCY ANEMIA AND REDUCTION OF SERUM PHOSPHATE IN PATIENTS WITH NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE Geoffrey Block Geoffrey Block 1 Denver Nephrologists PC, Denver, CO Steven Fishbane Steven Fishbane 2 North Shore-LIJ Health System, Great Neck, NY Shay Shemesh Shay Shemesh 3 Keryx Biopharmaceuticals, New York, NY Amit Sharma Amit Sharma 3 Keryx Biopharmaceuticals, New York, NY Myles Wolf Myles Wolf 4 Northwestern University, Chicago, IL Glenn Chertow Glenn Chertow 5 Stanford University, Stanford, CA Abstract Introduction and Aims: Iron deficiency anemia is common in patients with non-dialysis dependent chronic kidney disease and often remains untreated. In this same population, serum phosphate above 4.0 mg/dl is associated with progressive loss of kidney function, cardiovascular events and mortality. Methods: We performed a double-blind, placebo-controlled randomized trial in patients with non-dialysis dependent chronic kidney disease. One-hundred forty nine patients were randomized 1:1 to ferric citrate coordination complex or matching placebo for 12 weeks. Study drug was titrated to achieve a serum phosphate 3.0-3.5 mg/dl. Inclusion criteria included eGFR < 60 ml/min/1.73m2, transferrin saturation (TSAT) <30%, serum ferritin <300 ng/ml and serum phosphate ≥4.0-6.0 mg/dl. Use of intravenous iron or erythropoiesis stimulating agents was prohibited. Primary endpoints were change in TSAT and serum phosphate from baseline to end of study. Results: Ferric citrate treatment significantly increased TSAT from 22 ± 7% to 32 ± 14% and reduced serum phosphate from 4.5 ± 0.6 mg/dL to 3.9 ± 0.6 mg/dL, each p<0.001 versus placebo in whom transferrin saturation remained stable at 21 ± 8% and serum phosphate declined by 0.3 mg/dl. Ferric citrate increased hemoglobin from 10.5 ± 0.8 g/l to 11.0 ± 1.0 (p<0.001 versus placebo), reduced urinary phosphate 39% (p<0.001 versus placebo) and reduced intact FGF23 from 319 ± 577 to 200 ± 386 RU/ml (p=0.017 versus placebo). The incidence and severity of adverse effects were similar between treatment arms. No subject developed sustained hypophosphatemia. Conclusions: Ferric citrate safely and effectively repletes iron stores, increases hemoglobin without the need for intravenous iron or ESAs and reduces serum phosphate and urinary phosphate excretion in patients with non-dialysis dependent chronic kidney disease. SP239RISK FACTORS FOR THE PREVALENCE AND PROGRESSION OF ATHEROSCLEROTIC PLAQUE IN CHRONIC KIDNEY DISEASE. THE NEFRONA STUDY Marta Gracia Marta Gracia 1 Biomedical Research Institute, Lleida, Spain David Arroyo David Arroyo 2 University Hospital Arnau de Vilanova, Lleida, Spain Àngels Betriu Àngels Betriu 1 Biomedical Research Institute, Lleida, Spain Jose Manuel Valdivielso Jose Manuel Valdivielso 1 Biomedical Research Institute, Lleida, Spain Elvira Fernández Elvira Fernández 2 University Hospital Arnau de Vilanova, Lleida, Spain Abstract Introduction and Aims: Intima Media Thickness (IMT) and atherosclerotic plaque are well-known factors of cardiovascular risk scoring, especially in Chronic Kidney Disease (CKD). Limited longitudinal studies exist regarding the relationship between stage of chronic kidney disease and risk factors for progression of atherosclerotic burden. Methods: Multicenter, observational and prospective study in CKD Spanish patients without cardiovascular disease (NEFRONA). They were studied according to a standardized protocol including clinical and biochemical data, ankle-brachial index (ABI), carotid and femoral ultrasound at baseline and after 12 months to assess the atherosclerotic plaque progression. Progression was defined as formation of new atherosclerotic plaques in patients without or with a single plaque at baseline. The statistical level of significance was fixed to 0.05. Results: We included 476 CKD patients (193 Stage 3, 149 Stages 4-5 and 134 on dialysis). Prevalence of atherosclerotic plaque was 68.7% and plaque progression occurred in 38.7% patients, without differences between CKD stages. Variables significantly and positively related to atherosclerosis plaque at baseline were male sex [HR= 4.694, 95% CI (1.883-11.698)], age [HR=1.144, 95% CI (1.095-1.195)], smoke [HR=2.378, 95% CI (1.11-5.09)], pathologic IMT [HR=4.15; 95% CI (1.444-11.929)] and pathologic ABI [HR=6.911; 95% CI (2.271-21.027)]. Conversely, 25-hydroxi-vitamin-D levels were negatively related to atherosclerosis [HR=0.899, 95 % CI (0.855-0.946]. Atherosclerosis progression was significantly related to CKD stage progression [HR=7.553; 95% CI (1.079-52.85)], age [HR=1.076; 95% CI (1.008-1.150)], high systolic blood pressure [HR=1.032; 95% CI (1.003-1.062)], IMT [HR=1558; 95% CI(2.94-825935)] and glucose increase [HR=1.031; 95% CI (1.002-1.059)]. Conclusions: Prevalence of atherosclerotic plaque is high in all CKD stages. Atherosclerotic plaque progression is fast. Therefore, longitudinal ultrasound monitoring of plaque formation may be useful in cardiovascular risk progression assessment. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP240CIRCULATING EXTRACELLULAR VESICLES IN PATIENTS WITH END STAGE CHRONIC KIDNEY DISEASE: NEW UREMIC TOXINS INVOLVED IN INFLAMMATION, ENDOTHELIAL DYSFUNCTION AND VASCULAR CALCIFICATION Vincenzo Cantaluppi Vincenzo Cantaluppi 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Davide Medica Davide Medica 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Alessandro D Quercia Alessandro D Quercia 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Sergio Dellepiane Sergio Dellepiane 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Massimo Gai Massimo Gai 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Gianluca Leonardi Gianluca Leonardi 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Cesare Guarena Cesare Guarena 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Massimiliano Migliori Massimiliano Migliori 2 Nephrology and Dialysis Unit, Versilia Hospital, Camaiore, (Lu), Italy Vincenzo Panichi Vincenzo Panichi 2 Nephrology and Dialysis Unit, Versilia Hospital, Camaiore, (Lu), Italy Luigi Biancone Luigi Biancone 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Giovanni Camussi Giovanni Camussi 1 Nephrology, Dialysis and Kidney Transplantation Unit, Torino, Italy Abstract Introduction and Aims: Inflammation, endothelial dysfunction and vascular calcifications are common features of patients with end stage chronic kidney disease (CKD). CKD is associated with high mortality rates due to multiple co-morbidities, particularly cardiovascular diseases (CVD). The pathogenetic mechanisms of CKD-associated CVD are not only related to traditional factors such as hypertension and dyslipidemia, but also to endothelial dysfunction, inflammatory mediators and water soluble or protein-bound uremic toxins (UT). Among these detrimental mediators, extracellular vesicles (EV) are nanoparticles that represent a new concept of inter-cellular cross-talk through the transfer of proteins, mRNAs and microRNAs to target cells. Our main working hypothesis is that EV may synergize with UT in the induction of CVD, altering the function of endothelial cells (EC), smooth muscle cells (SMC) and endothelial progenitors (EPC). The aim of this study was to isolate and characterize circulating EV in CKD patients and to study their role in EC, SMC and EPC dysfunction. Methods: We analyzed plasma drawn from 65 end stage CKD patients undergoing standard hemodialysis. Plasma EV were evaluated by Nanotrack (Nanosight) and FACS analysis. Circulating CD34+CD133+flk-1+ EPC were evaluated by FACS on patients' whole blood. EV isolated from CKD patients' plasma were added to cultured human EC, SMC and EPC evaluating apotosis, angiogenesis and calcification capacity. Results: In comparison to healthy subjects, CKD patients showed an increased concentration of plasma EV. FACS analysis revealed that plasma EV originated from different cell types including microvascular endothelial cells, monocytes, neutrophils, lymphocytes, platelets and erythrocytes. In addition, EV expressed on their surface molecules involved in inflammation, coagulation and apoptosis such as Tissue Factor, the terminal complement factor C5b9 (MAC), CD40-ligand, Fas-Ligand and different proteins of integrin and selectin families. Plasma EV inversely correlated with the percentage of circulating CD34+CD133+flk-1+ EPC. By contrast, EV direcly correlated with plasma levels of homocysteine, ADMA and C reactive protein. FACS and confocal microscopy analysis showed that plasma EV were internalized in isolated human EC, SMC and EPC. In EC, plasma EV increased leukocyte adhesion, triggered apoptosis and reduced their pro-angiogenic properties on Matrigel-coated plates. These effects were related to EV-induced decrease of eNOS expression and consequent NO production. In SMC, plasma EV increased calcification capacity as assesed by alizarin red staining and qRT-PCR for Runx2 mRNA. In EPC, plasma EV induced apoptosis and reduced VEGF release. All the described detrimental effects induced by EV on EC, SMC and EPC were enhanced by co-incubation with protein bound UT such as p-cresyl sulphate and indoxyl sulphate. By contrast, the biological activities of EV were significantly decreased by their pre-treatment with RNase, the enzyme able to destroy mRNA and microRNA within EV. Conclusions: Plasma EV concentrations are significantly increased in end stage CKD patients. EV originate from different cell types and may sinergyze with protein bound UT in the development of EC, SMC and EPC injury. The transfer of proteins, mRNA and microRNA from EV to target cells may have a key role in inflammation, endothelial dysfunction, vascular calcifications and CVD in patients with end stage CKD. SP241EFFICACY AND SAFETY OF PA21 AND SEVELAMER CARBONATE IN HAEMODIALYSIS PATIENTS WITH OR WITHOUT DIABETES: A POST HOC ANALYSIS OF A PHASE 3 STUDY Adrian Covic Adrian Covic 1 ‘Grigore.T. Popa’ University of Medicine and Pharmacy, Iasi, Romania Markus Ketteler Markus Ketteler 2 Coburg Clinic and KfH-Dialysis Center, Coburg, Germany Anjay Rastogi Anjay Rastogi 3 University of California, Los Angeles, CA Bruce Spinowitz Bruce Spinowitz 4 New York Hospital Queens, New York, NY Stuart M Sprague Stuart M Sprague 5 Northshore University Health System University of Chicago Pritzker School of Medicine, Evanston, IL Jaco Botha Jaco Botha 6 Vifor Pharma, Glattbrugg, Switzerland Viatcheslav Rakov Viatcheslav Rakov 6 Vifor Pharma, Glattbrugg, Switzerland Jürgen Floege Jürgen Floege 7 RWTH University Hospital Aachen, Aachen, Germany Abstract Introduction and Aims: A randomized, open-label, Phase 3 study assessed PA21, a polynuclear iron(III)-oxyhydroxide phosphate binder, vs sevelamer carbonate (SEV), in dialysis patients with hyperphosphatemia. Methods: 1,059 patients were randomized to PA21 (1.0-3.0 g/day; initial dose 1.0 g/day [2 tablets/day]; n=710) or SEV (2.4-14.4 g/day; initial dose 4.8 g/day [6 tablets/day]; n=349) for a 12-week dose titration (dose changes only permitted for tolerability in Weeks 8-12), followed by 12 weeks' maintenance. Eligible patients were enrolled in a 28-week safety extension study. A post hoc analysis was undertaken to assess the efficacy and safety of PA21 and SEV over 52 weeks in patients with diabetes compared with those without diabetes. Results: In total, the full analysis set included 694 patients in the PA21 group (275 with and 419 without diabetes) and 347 patients in the SEV group (123 with and 224 without diabetes). Mean (± standard deviation [SD]) age was higher in patients with diabetes (PA21: 60±12 years; SEV: 62±11 years) vs those without diabetes (PA21: 54±14 years; SEV: 53±15 years). Mean body mass index was also higher in patients with diabetes (PA21: 31±7 kg/m2; SEV: 32±8 kg/m2) than in patients without diabetes (PA21: 28±6 kg/m2; SEV: 28±6 kg/m2). Mean baseline serum phosphorus was similar in patients with diabetes (PA21: 2.4±0.54 mmol/L; SEV: 2.4±0.57 mmol/L) to that in patients without diabetes (PA21: 2.5±0.61 mmol/L; SEV: 2.4±0.58 mmol/L), and mean change from baseline to the Week 52 endpoint was similar between diabetic patients (PA21:-0.6±0.66 mmol/L; SEV:-0.6±0.65 mmol/L) and non-diabetic patients (PA21:-0.6±0.68 mmol/L; SEV:-0.6±0.71mmol/L). A slightly lower mean daily number of tablets was taken by patients with diabetes (PA21: 3.0±1.1; SEV: 8.3±3.7) than by patients without diabetes (PA21: 3.5±1.3; SEV: 8.9±3.5). The proportion of patients experiencing treatment-emergent adverse events (TEAEs) was slightly higher in diabetic (PA21: 92%; SEV: 94%) vs non-diabetic (PA21: 87%; SEV: 85%) patients. No clinically meaningful changes in blood pressure, serum glucose or serum vitamin D concentrations were observed in patients with or without diabetes in either PA21 or SEV groups. Conclusions: These data indicate that PA21 is an effective and well tolerated phosphate binder in patients with diabetes, with no effect on serum glucose. One potential explanation for the slightly lower pill burden reported in patients with diabetes is that they may have had stricter dietary control and thus required fewer tablets. SP242POST HOC ANALYSIS OF SAFETY PROFILES BY PATIENT AGE IN A PHASE 3 STUDY OF PA21 AND SEVELAMER CARBONATE Jürgen Floege Jürgen Floege 1 RWTH University Hospital Aachen, Aachen, Germany Markus Ketteler Markus Ketteler 2 Coburg Clinic and KfH-Dialysis Center, Coburg, Germany Anjay Rastogi Anjay Rastogi 3 University of California, Los Angeles, CA Bruce Spinowitz Bruce Spinowitz 4 New York Hospital Queens, New York, NY Stuart M. Sprague Stuart M. Sprague 5 Northshore University Health System University of Chicago Pritzker School of Medicine, Evanston, IL Jaco Botha Jaco Botha 6 Vifor Pharma, Glattbrugg, Switzerland Peter Braunhofer Peter Braunhofer 6 Vifor Pharma, Glattbrugg, Switzerland Adrian Covic Adrian Covic 7 ‘Grigore.T. Popa’ University of Medicine and Pharmacy, Iasi, Romania Abstract Introduction and Aims: A randomized, open-label, Phase 3 study assessed PA21, a polynuclear iron(III)-oxyhydroxide phosphate binder, vs sevelamer carbonate (SEV), in dialysis patients with hyperphosphatemia. Methods: 1,059 patients were randomized to PA21 (1.0-3.0 g/day; initial dose 1.0 g/day [2 tablets/day]; n=710) or SEV (2.4-14.4 g/day; initial dose 4.8 g/day [6 tablets/day]; n=349) for a 12-week dose titration (dose changes only permitted for tolerability in Weeks 8-12), followed by 12 weeks' maintenance. Eligible patients were enrolled in a 28-week safety extension study. A post hoc analysis of treatment-emergent adverse events (TEAEs) over 52 weeks by age was performed in the safety set (N=1,055). Results: The analysis included 752 patients <65 years and 303 patients ≥65 years. Similar proportions of patients <65 years experienced TEAEs with PA21 or SEV; these proportions did not change substantially in patients ≥65 years (Table). Rates of severe and serious TEAEs were lower in patients <65 years vs ≥65 years. A significantly higher proportion of PA21 patients than SEV patients withdrew due to TEAEs, in both age groups. Rates of hyperphosphatemia TEAEs were lower in patients ≥65 years (PA21: 12.2%, SEV: 6.6%) vs those <65 years (PA21: 20.2%, SEV: 17.8%). Rates of diarrhoea were significantly higher with PA21 than with SEV in patients <65 years, but there was no significant difference between treatment groups in patients ≥65 years (Table). Conclusions: There was a higher rate of severe and serious TEAEs in patients ≥65 years vs <65 years, and a higher rate of some gastrointestinal TEAEs was observed in patients ≥65 years. The observed trends were not always consistent between treatment groups. Open in new tabDownload slide Open in new tabDownload slide SP243A NEW METHOD FOR THE APPROXIMATION OF CORRECTED CALCIUM IN CHRONIC KIDNEY DISEASE PATIENTS Yoshio Kaku Yoshio Kaku 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Susumu Ookawara Susumu Ookawara 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Haruhisa Miyazawa Haruhisa Miyazawa 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Kiyonori Ito Kiyonori Ito 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Yuichirou Ueda Yuichirou Ueda 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Keiji Hirai Keiji Hirai 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Taro Hoshino Taro Hoshino 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Honami Mori Honami Mori 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Aoi Nabata Aoi Nabata 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Izumi Yoshida Izumi Yoshida 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Kaoru Tabei Kaoru Tabei 1 Saitama Medical Center, Jichi Medical University, Saitama, Japan Abstract Introduction and Aims: The conventional calcium correction formula (Payne), corrected calcium (TCa corr) (mg/dL) = TCa (mg/dL) + 1.97 × (4 - albumin (mg/dL)), is broadly applied for the estimation of serum calcium. However, this formula excluded chronic kidney disease (CKD) patients seen in renal medicine. The aim of this study was to derive a new formula for TCa corr approximation using clinical parameters in CKD patients. Methods: In this retrospective study, a total of 2503 venous samples were collected from 942 stable CKD patients and levels of total calcium ([TCa] mg/dL), ionized calcium ([iCa2+] mmol/L), phosphate (mg/dL), albumin (g/dL), pH and other clinical parameters were measured. We assumed the gold standard for TCa corr to be equal to 8 times the iCa2+ value as considered in previous reports. Then, we performed stepwise multiple linear regression analysis using the clinical parameters and arrived at simple formula for TCa corr approximation. Furthermore, we examined the correlation between the new formula and the gold standard for TCa corr, and compared this correlation with that shown by the conventional, Jain, and Ferrali formulas. Results: Using multiple linear regression analysis, the following formula was derived: TCa corr (mg/dL) = TCa + 0.25 (4 - albumin) + 4 (8 - pH) - 0.1 (p + 15). Approximated TCa corr using this formula showed a positive linear correlation with the gold standard of TCa corr (r = 0.83, p < 0.001), and had superior agreement compared to all of the other formulae (conventional formula: r = 0.23, Jain: r = 0.65, Ferrali = 0.38 vs. gold standard of TCa corr,). Conclusions: In CKD patients, correction of TCa should include not only albumin but also pH and phosphate, and in this study, we have devised a simple formula for the approximation of TCa corr. SP244LONG-TERM EFFECTS OF SOTATERCEPT COMPARED WITH PLACEBO FOR CORRECTION OF ANEMIA IN HEMODIALYSIS SUBJECTS: INTERIM ANALYSIS OF ACE-011-REN-001 PHASE 2A STUDY Mohamed El-Shahawy Mohamed El-Shahawy 1 Academic Medical Research Institute, Los Angeles, CA James Cotton James Cotton 2 Tyler Nephrology Associates PC, Tyler, TX Jeffrey Kaupke Jeffrey Kaupke 3 Nephrology Specialist Medical Group, Orange, CA Thomas D. Wooldridge Thomas D. Wooldridge 4 Nephrology & Hypertension Associates Ltd, Tupelo, MS Michael Weiswasser Michael Weiswasser 5 Celgene Corporation, Warren, NJ William T Smith William T Smith 5 Celgene Corporation, Warren, NJ Abstract Introduction and Aims: This ongoing randomized, single-blind, placebo-controlled study of sotatercept (ACE-011), an ActRIIA-IgG1 fusion protein ligand trap, for the correction of anemia in hemodialysis (HD) subjects evaluated the pharmacokinetics (PK), safety, tolerability, and hemoglobin (Hb) effect of sotatercept and explored effects on bone mass and vascular calcification. Methods: Subjects who were erythropoietin-stimulating agent (ESA) responsive were washed out of their ESA effect until Hb was <10 g/dL, and then randomized to sotatercept or placebo (PBO). We present the interim results for PK, safety, Hb, and home blood pressure (BP) effects of the completed treatment phase of PBO (n=5) vs. sotatercept 0.3 mg/kg (n=9) and 0.5 mg/kg (n=8) administered SC every 28 days up to 8 dose cycles, without intra-subject dose escalation permitted. Treatment failures were rescued with ESA or transfusion. Enrolment in the 0.7 mg/kg group is ongoing. Results: Cumulative PK shows dose-dependent increases in Cmax and AUC, and an estimated terminal half-life of 23-25 days. Cumulative safety shows that treatment-emergent adverse events occurred in 80%, 89%, and 75% and serious events in 40%, 44%, and 13% of PBO, 0.3, and 0.5 mg/kg subjects, respectively. Events were mostly mild to moderate, unrelated to study drug, mostly similar between groups, and generally consistent with subjects’ medical histories. No anti-drug antibodies, injection site reactions, or hypersensitivity reactions were observed. One death occurred in the PBO group. Baseline Hb levels were 9.7, 9.3, and 8.9 g/dL in PBO, 0.3, and 0.5 mg/kg groups. In the first 28-day dose cycle, peak mean Hb responses were 0.0, 0.5, and 0.8 g/dL and rescue was required in 40%, 12%, and 0% in the PBO, 0.3, and 0.5 mg/kg groups. During the 225-day treatment phase: a) the proportion of subjects requiring rescue was 60%, 78%, and 62% in the PBO, 0.3, and 0.5 mg/kg groups; b) the proportion of subjects achieving the target Hb increase (≥1 g/dL increase from baseline) was 40%, 33%, and 50% in the PBO, 0.3, and 0.5 mg/kg groups; c) excluding 2 subjects with major protocol violations (0.3 and 0.5 mg/kg, n=1 each), the proportion of subjects achieving the target Hb increase was 40%, 38%, and 57% in the PBO, 0.3, and 0.5 mg/kg groups; d) the desired Hb range (10-12 g/dL) was maintained for 18%, 19%, and 28% of all possible dose cycles in the PBO, 0.3, and 0.5 mg/kg groups; e) excluding the 2 protocol violations, the Hb range was maintained for 18%, 22%, and 32% of cycles in the PBO, 0.3, and 0.5 mg/kg groups. There were no dose-dependent changes in home BP. Conclusions: PK parameters were similar to Phase 1. Sotatercept appears to be safe and tolerated in HD patients. There is an apparent dose-dependent peak Hb response in the first dose cycle and improved long-term Hb efficacy without an increase in home BP. SP245COMPARISON OF SAFETY PROFILES OF PA21 AND SEVELAMER CARBONATE IN A POST HOC ANALYSIS OF A PHASE 3 STUDY Adrian Covic Adrian Covic 1 ‘Grigore.T. Popa’ University of Medicine and Pharmacy, Iasi, Romania Markus Ketteler Markus Ketteler 2 Coburg Clinic and KfH-Dialysis Center, Coburg, Germany Anjay Rastogi Anjay Rastogi 3 University of California, Los Angeles, CA Bruce Spinowitz Bruce Spinowitz 4 New York Hospital Queens, New York, NY Stuart M Sprague Stuart M Sprague 5 Northshore University Health System University of Chicago Pritzker School of Medicine, Evanston, IL Jaco Botha Jaco Botha 6 Vifor Pharma, Glattbrugg, Switzerland Peter Braunhofer Peter Braunhofer 6 Vifor Pharma, Glattbrugg, Switzerland Jürgen Floege Jürgen Floege 7 RWTH University Hospital Aachen, Aachen, Germany Abstract Introduction and Aims: A randomized, open-label, Phase 3 study assessed PA21, a polynuclear iron(III)-oxyhydroxide phosphate binder, vs sevelamer carbonate (SEV), in dialysis patients with hyperphosphatemia. Methods: 1,059 patients were randomized to PA21 (1.0-3.0 g/day; initial dose 1.0 g/day [2 tablets/day]; n=710) or SEV (2.4-14.4 g/day; initial dose 4.8 g/day [6 tablets/day]; n=349) for a 12-week dose titration (dose changes only permitted for tolerability in Weeks 8-12), followed by 12 weeks' maintenance. Eligible patients were enrolled in a 28-week safety extension study. Treatment-emergent adverse events (TEAEs) over 52 weeks were analysed post hoc in all randomized patients who took ≥1 dose of study medication (N=1,055). Results: TEAEs were reported in 88.8% of PA21 and 88.5% of SEV patients. Respective rates of serious (26.6% and 29.6%) and severe (16.0% and 17.5%) TEAEs were similar between treatment groups. Rates of withdrawal due to TEAEs were 20.9% (PA21) and 10.3% (SEV); the difference was mainly driven by mild, transient diarrhoea with PA21 (mostly occurring during the first 6 months of the study). There was a significantly higher relative risk (RR) of mild and moderate diarrhoea with PA21 vs SEV, but no significant difference in RR of severe diarrhoea between treatment groups (Table). Patients receiving SEV had a significantly higher RR of nausea, decreased appetite and constipation vs PA21 (Table). Rates of hyperphosphatemia TEAEs were 18.0% and 14.4% in PA21 and SEV groups, respectively, with no significant difference in RR between groups (RR: 1.3; p=0.146). A significantly higher RR of hyperparathyroidism was seen with SEV than with PA21 (incidence: 14.1% vs 8.6%; RR: 0.6; p=0.007). Conclusions: Although rates of serious and severe TEAEs were similar between PA21 and SEV treatment groups, some differences were observed between groups, particularly in terms of gastrointestinal TEAE profile. Open in new tabDownload slide Open in new tabDownload slide SP246EFFECT OF 5/6 NEPHRECTOMY ON THE EXPRESSION OF HIPPOCAMPAL POLYAMINES IN A RODENT MODEL OF CHRONIC KIDNEY DISEASE Tilo Hanowski Tilo Hanowski 1 Martin Luther University Halle-Wittenberg, Faculty of Medicine, Halle (Saale), Germany Kristin Jäger Kristin Jäger 1 Martin Luther University Halle-Wittenberg, Faculty of Medicine, Halle (Saale), Germany Song Rong Song Rong 2 Hannover Medical School, Hannover, Germany Tammo Lesch Tammo Lesch 1 Martin Luther University Halle-Wittenberg, Faculty of Medicine, Halle (Saale), Germany Franziska Knöfel Franziska Knöfel 1 Martin Luther University Halle-Wittenberg, Faculty of Medicine, Halle (Saale), Germany Heike Kielstein Heike Kielstein 1 Martin Luther University Halle-Wittenberg, Faculty of Medicine, Halle (Saale), Germany Abstract Introduction and Aims: The prevalence of chronic kidney disease (CKD) is increasing worldwide. Epidemiological studies show that cognitive impairment progresses with the deterioration of renal function, best epitomized by marked cognitive impairment of patients on dialysis as compared to the general population. The aim of our study was to evaluate the effect of CKD on the expression of spermine synthase (SMS) and spermine oxidase (SMOX) in hippocampi of Sprague Dawley (SD) rats. These enzymes are involved in polyamine cycle. Polyamines may affect the memory in different ways, for example they are ligands for NMDA receptors and influence cell growth and aging. Methods: SD rats (14 weeks old, n=30) were divided into two groups. The first group was sham-operated (n=13) and the other underwent 5/6 nephrectomy (n=17). All animals were sacrificed for blood and tissue sampling, 6 weeks after the operation. Rat brains were formalin-fixed and consecutively hippocampal sections were immunohistochemically stained. Furthermore qRT-PCR was performed with whole brains. Results: As compared to the control group CKD rats showed altered SMS and SMOX protein and gene expression. In both groups the protein expression was region-specific. Conclusions: These data suggest that CKD influences the hippocampal expression of polyamines affecting the cognitive potential and herewith contribute to the cognitive deficits of CKD patients. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP247ELEVATED MINERALOCORTICOID LEVELS ARE ASSOCIATED WITH INCREASED RISK OF REQUIRING RENAL REPLACEMENT THERAPY Emily P. McQuarrie Emily P. McQuarrie 1 Western Infirmary Glasgow, Glasgow, United Kingdom 2 University of Glasgow, Glasgow, United Kingdom Patrick B. Mark Patrick B. Mark 1 Western Infirmary Glasgow, Glasgow, United Kingdom 2 University of Glasgow, Glasgow, United Kingdom E. Marie Freel E. Marie Freel 2 University of Glasgow, Glasgow, United Kingdom Alison Taylor Alison Taylor 1 Western Infirmary Glasgow, Glasgow, United Kingdom 2 University of Glasgow, Glasgow, United Kingdom Alan G. Jardine Alan G. Jardine 1 Western Infirmary Glasgow, Glasgow, United Kingdom 2 University of Glasgow, Glasgow, United Kingdom Abstract Introduction and Aims: Elevated aldosterone levels have been shown to be associated with adverse cardiovascular outcomes in the general population and sudden cardiac death in dialysed patients. In chronic kidney disease (CKD), blockade of the mineralocorticoid receptor (MR) has been shown to reduce proteinuria and regress left ventricular hypertrophy. In addition, we have previously shown that the mineralocorticoid precursor deoxycorticosterone (DOC) is associated with left ventricular mass in CKD patients. The aim of this study was to investigate whether mineralocorticoid levels were associated with renal outcomes in CKD. Methods: 70 patients with CKD stages 3 or 4 were recruited. Plasma aldosterone concentration (PAC) was measured by radioimmunoassay (Siemens). Plasma renin concentration (PRC) was measured by an automated immunochemiluminometric assay (Diasorin). Patients also provided a 24-hour urine collection for measurement of the urinary metabolites of aldosterone (tetrahydroaldosterone; THAldo) or DOC (THDOC) by gas chromatography-mass spectrometry as well as urinary electrolytes and protein quantification. Patients were censored at time of death or RRT. Results: At baseline, 76% were male, mean age was 58 (13) years, mean eGFR 40 (24) ml/min/1.73m2 and median urinary protein excretion was 1.0 (0.3-2.8) g/24h. Median follow up was 1490 (1257-1597) days. 13 patients required renal replacement therapy (RRT) for CKD and 11 patients died. Patients who required RRT had significantly higher levels of proteinuria and lower eGFR at baseline. Plasma and urinary steroid levels were not associated with level of renal function at baseline. Patients who required dialysis had significantly higher urinary THDOC excretion (p=0.004), THALDO excretion (0.02) and plasma aldosterone concentration (p=0.01) at time of study inclusion. On binary logistic regression, THDOC was a significant univariate predictor (p=0.008), as was THALDO (p=0.02) and plasma aldosterone (p=0.02) of requiring RRT. There was no significant difference in the frequency of prescribed ACE inhibitors between those requiring RRT and those not. No significant association between steroid levels and death was seen. Conclusions: These novel data demonstrate an association between elevated levels of mineralocorticoids and the risk of requiring renal replacement therapy. These data support the need for further study of the benefits of MR blockade in CKD. SP248THE EFFECT OF RHUEPO ON NO AND ET - 1 IN THE CHRONIC HEMODIALYSIS PATIENTS Cai-Li Wang Cai-Li Wang 1 The First Affiliated Hospital of Bao Tou Medical College, Bao Tou, China Yu Du Yu Du 1 The First Affiliated Hospital of Bao Tou Medical College, Bao Tou, China Lei Nan Lei Nan 1 The First Affiliated Hospital of Bao Tou Medical College, Bao Tou, China Abstract Introduction and Aims: To investigate the effect of recombinant Human erythropoietin ( rhuEpo) on Nitric Oxide(NO), Endothelin - 1 ( ET - 1) and Angiotension - II(Ang II) in chronic hemodialysis patients. Methods: Eighty patients on chronic hemodialysis were enrolled in this randomized, controlled study. Forty - three received rhuEpo (HDepo n = 43) and thirty - seven did not (HD n = 37). According to the blood pressure, each group was sub - divided into two groups, HDepo with hypertention (HDepo - 1 group n = 23), HDepo with normal blood pressure (HDepo - 2 group n = 20), HD with hypertention (HD - 1 group n = 19), HD with normal blood pressure (HD - 2 group n = 18). Twenty uremia patients who did not receive hemodialysis therapy and twenty normal adults were chosen as control group (CON group). The NO level was measured by colorimetry. The ET - 1 level and the Ang IIlevel were measured by radioimmunoassay (RIA). Results: The NO level, ET - 1 level, Ang IIlevel in uremia patients receiving HD therapy were higher than those in normal control group( P < 0. 001). The NO level in serum of hemodialysis patients was higher than that in patients did not receive hem dialysis therapy. The ET - 1 level and Ang II level were higher than those in patients did not receive hemodialysis therapy ( P <0. 05). After three months’therapy, the NO consistency in serum in HD group declined after the rHuepo therapy, it was lower than that of normal control group. While the ET - 1 consistency and Ang IIconcentration raised( P < 0. 05). After the therapy, diastolic pressure, systolic pressure, mean arterial pressure of HDepo group were all higher than those of HD group( P < 0. 001). The increase in blood pressure correlated with the decline of the NO concentration as well as increase in ET -1 and Ang IIconcentration. Conclusions: Erythropoietin can reduce serum NO concentration in chronic hemodialysis patients.It also can raise ET - 1 and Ang IIconcentration. Hypertention caused by rHuepo was associated with decrease in NO and increase in ET - 1 and Ang IIconcentration. Use EPO before and after NO, ET -1, Ang - IIserum level changes group . N . NO(μmol/L) . . ET - 1 (ng/ L) . . Ang II (ng/ L) . . . . Before using EPO . After using EPO . Before using EPO . After using EPO . Before using EPO . After using EPO . HDepo 43 146. 63 ± 67. 20 99. 99 ±51. 99** 259. 78 ±115. 41 334. 31 ±115. 01* 211. 66 ±112. 16 268. 20 ±111. 75* HD 37 135. 54 ± 60. 94 142. 28 ±63. 17 246. 93 ±112. 79 204. 70 ±99. 29 215. 10 ±100. 93 CON 20 76. 48 ± 19. 32 46. 11 ±9. 04 46. 77 ±25. 21 group . N . NO(μmol/L) . . ET - 1 (ng/ L) . . Ang II (ng/ L) . . . . Before using EPO . After using EPO . Before using EPO . After using EPO . Before using EPO . After using EPO . HDepo 43 146. 63 ± 67. 20 99. 99 ±51. 99** 259. 78 ±115. 41 334. 31 ±115. 01* 211. 66 ±112. 16 268. 20 ±111. 75* HD 37 135. 54 ± 60. 94 142. 28 ±63. 17 246. 93 ±112. 79 204. 70 ±99. 29 215. 10 ±100. 93 CON 20 76. 48 ± 19. 32 46. 11 ±9. 04 46. 77 ±25. 21 Use EPO before and after NO, ET -1, Ang - IIserum level changes group . N . NO(μmol/L) . . ET - 1 (ng/ L) . . Ang II (ng/ L) . . . . Before using EPO . After using EPO . Before using EPO . After using EPO . Before using EPO . After using EPO . HDepo 43 146. 63 ± 67. 20 99. 99 ±51. 99** 259. 78 ±115. 41 334. 31 ±115. 01* 211. 66 ±112. 16 268. 20 ±111. 75* HD 37 135. 54 ± 60. 94 142. 28 ±63. 17 246. 93 ±112. 79 204. 70 ±99. 29 215. 10 ±100. 93 CON 20 76. 48 ± 19. 32 46. 11 ±9. 04 46. 77 ±25. 21 group . N . NO(μmol/L) . . ET - 1 (ng/ L) . . Ang II (ng/ L) . . . . Before using EPO . After using EPO . Before using EPO . After using EPO . Before using EPO . After using EPO . HDepo 43 146. 63 ± 67. 20 99. 99 ±51. 99** 259. 78 ±115. 41 334. 31 ±115. 01* 211. 66 ±112. 16 268. 20 ±111. 75* HD 37 135. 54 ± 60. 94 142. 28 ±63. 17 246. 93 ±112. 79 204. 70 ±99. 29 215. 10 ±100. 93 CON 20 76. 48 ± 19. 32 46. 11 ±9. 04 46. 77 ±25. 21 SP249CLOT STRUCTURE PREDICTS MORTALITY IN CHRONIC KIDNEY DISEASE K: Hess K: Hess A. Savvaidis A. Savvaidis K. Lysaja K. Lysaja N. Dimkovic N. Dimkovic J. Floege J. Floege N. Marx N. Marx Georg Schlieper Georg Schlieper 1 Uniklinik RWTH Aachen, Aachen, Germany Abstract Introduction and Aims: Chronic kidney disease (CKD) is associated with both coagulopathy and increased cardiovascular mortality. Impaired fibrin clot lysis is known to predispose to atherothrombotic disease and clots with compact structure and impaired fibrinolysis are associated with premature and more severe cardiovascular disease. Patients with CKD are known to have a prothrombotic clot structure characterized by small pores and resistance to fibrinolysis, however the impact on outcome in CKD patients is unknown. Therefore, the aim of the current work was to investigate whether clot structure is associated with outcome in patients with CKD. Methods: Fibrin clot structure and lysis were determined in plasma of 172 hemodialysis patients (59±11y, 54% male) using a validated turbidimetric assay. Plasma levels of fibrinogen were analysed by ELISA. Fibrinogen was purified from 6 healthy control individuals and 6 patients with CKD stage IV using a calcium dependent IF-1 monoclonal antibody. Results: Compared to controls with normal renal function plasma of CKD patients exhibited a denser clot structure (0.26±0.01 (control) vs. 0.44±0.04 (CKD) AU, respectively; p<0.01) and prolonged clot lysis (468±38 vs. 1274±134 sec respectively; p<0.01). Kaplan Meier analysis revealed that CKD patients with a denser clot structure had an increased mortality risk. Multivariate Cox regression model (adjusted for age, diabetes, gender, duration of dialysis and fibrinogen) confirmed the massive, independent risk prediction of denser clots (hazard ratio 76, confidence interval= 3 - 1800; p=0.007). Fibrinogen levels were not significantly related to outcome. To further analyse whether the effect of clot structure on mortality was dependent on fibrinogen we purified fibrinogen from healthy controls and CKD patients. Clot density of purified fibrinogen did not differ between both groups (0.15±0.01 and 0.16±0.01AU respectively; p=0.6) as did lysis time (3294±182 sec and 3290±209 sec respectively; p=0.9). Conclusions: A denser clot structure is a potent, independent predictor of mortality in hemodialysis patients. Using purified fibrinogen clot structure did not differ between CKD patients and controls, suggesting alterations of plasma and not fibrinogen as the driving factors in this context. SP250FABRY NEPHROPATHY (FN) OUTCOME AND THE IMPACT OF DIAGNOSTIC KIDNEY BIOPSIES AFTER 10 YEARS ENZYME REPLACEMENT THERAPY (ERT) R Skrunes R Skrunes 1 Haukeland University Hospital, Bergen, Norway 2 University of Bergen, Bergen, Norway K K Larsen K K Larsen 1 Haukeland University Hospital, Bergen, Norway 2 University of Bergen, Bergen, Norway E Svarstad E Svarstad 1 Haukeland University Hospital, Bergen, Norway 2 University of Bergen, Bergen, Norway C Tøndel C Tøndel 1 Haukeland University Hospital, Bergen, Norway 2 University of Bergen, Bergen, Norway Abstract Introduction and Aims: Recent studies have shown variable results concerning kidney function stability after long-term ERT, and beneficial effect on GFR and histology have been reported after 5 years (y) ERT in younger cohorts. There is a scarcity of morphologic data in FN patients, and we report 10 years clinical and morphologic single center follow-up data from a cohort of 12 patients with CKD stage 1 (6 male (M), 1 female (F)) or 2 (1 M and 4 F) and microalbuminuria, median age 26.5 (range 7-62) y at start of ERT (7 M, median age 18 (7-30) y, and 5 F, median age 51 (11-62) y). Methods: Iohexol GFR (iGFR), urine albumin-creatinine ratio (UACR) and cardiac assessments were done yearly, and a kidney biopsy was performed at baseline (B) and after 5 and 8-10 years. Cumulative ERT doses of agalsidase alfa and/or agalsidase beta (cumERT, mg/kg) were calculated. Significant decline of iGFR was defined as more than 1 ml/min/1.73m2/year. Results: Table 1 Clinical variables given as median values (range) Open in new tabDownload slide Open in new tabDownload slide iGFR declined in 3/7M and 3/5 F despite sustained morphologic reduction of Fabry Specific deposits in glomerular mesangial and endothelial cells, and unchanged clearance of podocyte deposits after 8-10 years. All patients with CKD2 received renoprotective treatment with ACEI/ARBs. Table 2 Clinical data of CKD progressors with FN. iGFR and UARC are baseline and 10 y follow-up. Open in new tabDownload slide Open in new tabDownload slide GN=de novo glomerulonephritis. VD=vascular disease.IF=interstitial fibrosis. LVH=left ventricular hypertrophy. CF=cardiac failure. HT=hypertension. AF=atrial fibrillation Conclusions: Follow-up kidney biopsies are important in unraveling the causes of progressive CKD in Fabry disease. Declining GFR during long-term ERT across a range of licensed doses in CKD 1-2 patients with microalbuminuria was associated with multifactorial non-Fabry specific mechanisms. SP251ACID-BASE BALANCE IN A PHASE 2 TRIAL OF ZS-9 FOR HYPERKALAEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE Bhupinder Singh Bhupinder Singh 1 Apex Research of Riverside, Riverside, CA Stephen R. Ash Stephen R. Ash 2 Indiana University Health Arnett, Lafayette, IN Philip T. Lavin Philip T. Lavin 3 Boston Biostatistics Research Foundation, Framingham, MA Alex Yang Alex Yang 4 Xelay Acumen, Inc., Belmont, CA Henrik S. Rasmussen Henrik S. Rasmussen 5 ZS Pharma, Inc., Coppell, TX Abstract Introduction and Aims: Metabolic acidosis is a common finding in patients with chronic kidney disease (CKD) and hyperkalaemia. Treatment of hyperkalaemia with polystyrene sulfonate (sodium or calcium) has uncertain efficacy and has been associated with poor tolerability and rare intestinal necrosis. ZS-9 is a selective cation exchanger designed to entrap excess potassium (K+) in exchange for sodium and hydrogen. ZS-9 absorbs ammonium as well as K+. In a multicenter, randomised, double-blind, placebo-controlled study, ZS-9 5g and 10g were shown to significantly reduce K+ vs placebo over 48 hr with excellent tolerability in patients with CKD. Here we report relevant acid-base related laboratory values with ZS-9 10g and placebo during this Phase 2 trial. Methods: Patients (glomerular filtration rate, 30-60 mL/min/1.73 m2; K+, 5-6 mmol/L) were randomized 2:1 to ZS-9 (n=60; 0.3g [n=12], 3g [n=24], or 10g [n=24]) or placebo (n=30) given orally three times daily for 2 days (and up to 2 more days if K+ ≥5.0 mmol/L; only 2 days needed for ZS-9 10g) with regular meals as in-patients. Serum and urine samples were collected through Day 7. RAAS inhibitors were continued during the study. Differences between groups were compared by unpaired t-test. Results: At baseline mean bicarbonate (28.1 mg/dL and 27.4 mg/dL) and urinary pH (5.8 and 5.7) were similar between ZS-9 10g and placebo, respectively. Bicarbonate increased more with ZS-9 10g than with placebo from Day 2-7. By Day 3 (14 hr after the last dose of ZS-9 10g) bicarbonate increased by +3.4 mg/dL with ZS-9 10g vs +0.4 mg/dL with placebo; at Day 6 the difference between groups was significant (p<0.05; Fig. 1). Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide Mean urinary pH increased with ZS-9 10g to 6.2 at Day 2 and 6.4 at Day 3 and remained higher than placebo through Day 7 (Fig. 2). Fig. 2 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide In contrast, urine pH fell in the placebo group to 5.6 at Day 2 and 5.5 at Day 3, resulting in significant (p<0.01) differences between groups at both time points. Mean blood urea nitrogen (BUN) decreased from baseline with ZS-9 10g vs placebo (p<0.05 for all evaluations between Day 2-7). There were no cases of significant hypocalcaemia (≤8 mg/dL), hypomagnesaemia (≤1.2 mmol/L), or hypokalaemia (≤3.0 mmol/L). Conclusions: Serum bicarbonate increased by approximately 12% from baseline with ZS-9 10g after 48 hr. Increases in urinary pH were also observed, suggesting that ZS-9 may improve acid-base balance in CKD patients with hyperkalaemia. The improvement in metabolic acidosis can be explained by removal of ammonium by ZS-9, as illustrated by the significant reduction in BUN. A two-stage Phase 3 trial that has just completed (N=753) will provide a larger dataset with which to evaluate ZS-9’s effects in patients with hyperkalaemia and the impact on acid-base balance. SP252AN OPEN-LABEL STUDY TO EVALUATE THE SAFETY OF DENOSUMAB IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) AND WITH CKD ON DIALYSIS Geoffrey A. Block Geoffrey A. Block 1 Denver Nephrologists PC, Denver, CO Ogo Egbuna Ogo Egbuna 2 Amgen Inc., Thousand Oaks, CA Steven Zeig Steven Zeig 3 Pines Clinical Research, Pembroke Pines, FL Pablo E. Pergola Pablo E. Pergola 4 Renal Associates PA, San Antonio, TX Bhupinder Singh Bhupinder Singh 5 Southwest Clinical Research Institute LLC, Tempe, AZ Ada Braun Ada Braun 2 Amgen Inc., Thousand Oaks, CA Yao Yu Yao Yu 2 Amgen Inc., Thousand Oaks, CA Winnie Sohn Winnie Sohn 2 Amgen Inc., Thousand Oaks, CA Desmond Padhi Desmond Padhi 2 Amgen Inc., Thousand Oaks, CA Abstract Introduction and Aims: Denosumab (Dmab) is a human monoclonal antibody that binds to RANK ligand (RANKL) to inhibit osteoclast-mediated resorption. Patients with CKD commonly have altered calcium homeostasis. Denosumab-induced inhibition of bone resorption may impact the contribution of exchangeable bone calcium to overall calcium homeostasis, thus affecting serum calcium levels. This study evaluated the incidence of hypocalcemia and safety parameters of patients with stage 4 or 5D CKD who were administered two subcutaneous (SC) doses of Dmab. Methods: Key eligibility criteria included age ≥18 years, hematology/clinical chemistry within normal limits (except renal panel), and intact parathyroid hormone levels, <110 pg/mL for stage 4 CKD patients and <300 pg/mL for stage 5D CKD patients. Patients were scheduled to receive two 120 mg doses of SC Dmab 28 days apart and were followed for 12 weeks after the second dose. End of study was at day 113. All patients received oral supplementation of at least 500 mg calcium and 400 IU vitamin D daily. The primary endpoint was the incidence of albumin-adjusted, serum calcium levels <7.0 mg/dL (1.75mmol/L) or symptomatic hypocalcemia. Additional endpoints included the incidence of adverse events (AEs) and changes in serum levels of calcium, phosphorus, and magnesium from baseline. Data were analyzed with descriptive statistics. Results: Of the 32 patients enrolled, 31 patients received 2 Dmab doses (15 stage 4 and 16 stage 5D); 1 stage 4 CKD patient received 1 dose before withdrawing consent. Overall, 50% of patients were men, 78% were white, and the median age (range) was 76 (38 to 94) years. Demographics were generally similar between the two groups. Rates of clinically significant hypocalcemia and adverse events at any point in the study are shown in the Table. The median percent change from baseline to end of study for stage 4 CKD patients versus stage 5D CKD patients was 0.00% vs ‑4.88% for calcium, -7.08% vs -8.98% for phosphorus, and 0.00% vs 1.92% for magnesium. The majority of hypocalcemic events were mild to moderate in severity. Conclusions: The use of denosumab was generally well tolerated in patients with stage 4 or 5D CKD. Some hypocalcemia events occurred despite oral calcium and vitamin D supplementation and suggest an important role of bone resorption for the maintenance of serum calcium levels in this patient population. Stage 5D CKD patients were more likely to experience clinically significant hypocalcemia and symptomatic hypocalcemia than stage 4 CKD patients. Stage 4 or 5D CKD patients receiving Dmab treatment should be monitored closely as part of routine care. Open in new tabDownload slide Open in new tabDownload slide SP253FERRIC CITRATE REDUCES FIBROBLAST GROWTH FACTOR 23 LEVELS IN PATIENTS WITH MODERATE CHRONIC KIDNEY DISEASE Geoffrey Block Geoffrey Block 1 Denver Nephrologists PC, Denver, CO Glenn Chertow Glenn Chertow 2 Stanford University, Palo Alto, CA Steven Fishbane Steven Fishbane 3 North Shore-LIJ Health System, Great Neck, NY Mariano Rodriguez Mariano Rodriguez 4 Hospital Universitario Reina Sofia, Cordoba, Spain Michael Chen Michael Chen 5 TCM Groups Inc, New Jersey, NJ Shay Shemesh Shay Shemesh 6 Keryx Biopharmaceuticals, New York, NY Amit Sharma Amit Sharma 6 Keryx Biopharmaceuticals, New York, NY Myles Wolf Myles Wolf 7 Northwestern University, Chicago, IL Abstract Introduction and Aims: Background: Concentrations of fibroblast growth factor 23 (FGF23) are elevated in patients with chronic kidney disease (CKD) and associated with higher risks of progressive loss of kidney function, cardiovascular events and mortality. In previous clinical trials, phosphate binders yielded mixed effects on FGF23 in patients with moderate CKD. This pre-specified secondary analysis evaluated the effect of the ferric citrate coordination complex, on FGF23 concentration in patients with moderate CKD. Methods: In a 12-week double blind trial, 149 participants with eGFR < 60 ml/min/1.73m2, serum phosphate ≥ 4.0 mg/dL, transferrin saturation ≤30% and serum ferritin ≤ 300 (ng/ml), were randomly assigned to receive placebo (n=74) or ferric citrate (n=75), 1-4 grams TID with meals titrated to achieve serum phosphate of 3.0 - 3.5 mg/dL. We measured FGF23 centrally using both a C-terminal assay (cFGF23; Immutopics) and an intact assay (iFGF23; Kainos). We compared the FGF23 responses to ferric citrate and placebo, and used linear regression to identify independent predictors of change in FGF23. Results: While significantly reducing serum phosphate by 0.6 mg/dl (P<0.001) and urine phosphate by 40% (P<0.001) compared to placebo, ferric citrate also significantly reduced levels of both cFGF23 (baseline to end of study: 467.9 to 315.6 vs. 511.1 to 579.2 RU/ml; P<0.001) and iFGF23 (319.0 to 199.5 vs. 263.2 to 292.7 pg/ml; P=0.017). At baseline, cFGF23 and iFGF23 were directly correlated with serum phosphate (iFGF23: r=0.28, P=0.002; cFGF23 r=0.27, P=0.002) and 24-hour urinary phosphate (iFGF23 r= 0.21, P=0.02; cFGF23 r=0.34, P=0.0001), but not with iron parameters or hemoglobin. In multivariable analyses that accounted for randomized treatment group, additional factors independently associated with the reduction in FGF23 from baseline to end of study included female sex, higher baseline FGF23, and a larger magnitude reduction in serum phosphate. A larger magnitude increase in transferrin saturation was independently associated with larger on-treatment reduction in cFGF23 but not iFGF23. Conclusions: Ferric citrate significantly reduced cFGF23 and iFGF23 by nearly 40% in association with a concomitant decrease in serum and urine phosphate. The reduction in cFGF23 was also associated with the magnitude of increase in transferrin saturation. These data suggest that ferric citrate lowers FGF23 in moderate CKD by simultaneously reducing intestinal phosphate absorption and repleting iron stores. Future studies should determine whether phosphate and FGF23 reduction by ferric citrate translate into cardiovascular and survival benefits in CKD. SP254ALTERATIONS OF LIPOPROTEIN CONSTITUTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE SHOWED NO EVIDENCE FOR AN INCREASE OF SMALL DENSE LDL - RESULTS FROM THE LURIC STUDY Graciela Delgado Graciela Delgado 1 Heidelberg University, Mannheim, Germany Marcus E Kleber Marcus E Kleber 1 Heidelberg University, Mannheim, Germany Tanja B Grammer Tanja B Grammer 1 Heidelberg University, Mannheim, Germany Bernhard K Kraemer Bernhard K Kraemer 1 Heidelberg University, Mannheim, Germany Winfried Maerz Winfried Maerz 1 Heidelberg University, Mannheim, Germany 2 Synlab Academy, Mannheim, Germany 3 Medical University of Graz, Graz, Austria Hubert Scharnagl Hubert Scharnagl 3 Medical University of Graz, Graz, Austria Abstract Introduction and Aims: The presence of chronic kidney disease is associated with a massive increase in cardiovascular risk and marked dyslipidemia which is characterized by low concentrations of HDL cholesterol (HDL-C) and high concentrations of triglycerides (TG). There is the hypothesis that also the concentration of small dense LDL (sdLDL) is increased. In our study we wanted to characterize the lipoprotein profile of patients with chronic kidney disease (CKD). Methods: In 3316 participants of the LURIC study lipoprotein particles were separated by ultracentrifugation and biochemically characterized. Average particle radius was calculated based on the method of Baumstark et al. eGFR was calculated using the CKD-EPI formula. Patients were stratified into three groups: G1: eGFR ≥ 90 ml/min/1.73m2 (n=1209), G2: eGFR 60-89 ml/min (n=1642) and G3: eGFR < 60 ml/min (n=456). Size and composition of lipoproteins were examined for an association with renal function. Since 48.3% of the study participants were treated with lipid-lowering agents we also repeated the analysis in the subgroup of patients not receiving lipid-lowering therapy. Results: Patients with impaired renal function had lower HDL-C and higher TG. The average particle radius was significantly increased (G1 vs G3: 8.25±0.21 vs 8.33±0.24 nm, P<0.001). In both LDL and HDL particles the fraction of TG increased. The ratio of LDL-TG to LDL-apoB increased from 0.36±0.12 in G1 to 0.44±0.14 in G3 (P<0.001) and the ratio from LDL-C to LDL-TG decreased from 4.03(3.21-5.04) in G1 to 3.14(2.58-3.99) in G3 (P<0.001). Apolipoprotein C3 was significantly elevated in G3 (P=0.003). The results in the subgroup of patients with no lipid-lowering therapy were basically the same. Conclusions: As expected, patients with chronic kidney disease showed lower values of HDL -C and higher levels of TG compared to patients with normal renal function. However, the decline in renal function was accompanied not by a decrease but by an increase in mean LDL particle radius and an enrichment of LDL particles with TG.Together with the observed increase of ApoC3, which in the liver inhibits both the lipoprotein lipase as well as the hepatic lipase, this indicates that the clearance of TG-rich lipoprotein remnants is delayed in CKD. We did not find evidence for a preferential accumulation of sdLDL. Plasmalipids according to eGFR . G1: eGFR≥90 ml/min/1.73m2 . G2: eGFR 60-89 ml/min/1.73m2 . G3: eGFR≤60 ml/min/1.73m2 . P . LDL-C (mg/dl) 117.3±35.2 117.4±33.6 111.3±34.2 0.002 LDL-TG (mg/dl) 29.84±10.44 31.61±11.86 35.62±13.70 <0.001 LDL-C/LDL-TG 4.04(3.21-5.04) 3.83(3.06-4.84) 3.14(2.58-3.99) <0.001 HDL-C (mg/dl) 39.1±10.7 39.0±10.8 36.8±11.0 <0.001 HDL-TG (mg/dl) 14.55±6.51 16.15±6.90 18.49±7.68 <0.001 HDL-C/HDL-TG 2.88(2.08-3.82) 2.55(1.93-3.40) 2.09(1.52-2.78) <0.001 TG (mg/dl) 144(107-200) 145(107-198) 159(118-209) 0.005 ApoC3 (mg/dl) 14.44±5.36 14.34±4.71 15.30±5.37 0.001 LDL radius (nm) 8.25±0.21 8.29±0.22 8.33±0.24 <0.001 . G1: eGFR≥90 ml/min/1.73m2 . G2: eGFR 60-89 ml/min/1.73m2 . G3: eGFR≤60 ml/min/1.73m2 . P . LDL-C (mg/dl) 117.3±35.2 117.4±33.6 111.3±34.2 0.002 LDL-TG (mg/dl) 29.84±10.44 31.61±11.86 35.62±13.70 <0.001 LDL-C/LDL-TG 4.04(3.21-5.04) 3.83(3.06-4.84) 3.14(2.58-3.99) <0.001 HDL-C (mg/dl) 39.1±10.7 39.0±10.8 36.8±11.0 <0.001 HDL-TG (mg/dl) 14.55±6.51 16.15±6.90 18.49±7.68 <0.001 HDL-C/HDL-TG 2.88(2.08-3.82) 2.55(1.93-3.40) 2.09(1.52-2.78) <0.001 TG (mg/dl) 144(107-200) 145(107-198) 159(118-209) 0.005 ApoC3 (mg/dl) 14.44±5.36 14.34±4.71 15.30±5.37 0.001 LDL radius (nm) 8.25±0.21 8.29±0.22 8.33±0.24 <0.001 Plasmalipids according to eGFR . G1: eGFR≥90 ml/min/1.73m2 . G2: eGFR 60-89 ml/min/1.73m2 . G3: eGFR≤60 ml/min/1.73m2 . P . LDL-C (mg/dl) 117.3±35.2 117.4±33.6 111.3±34.2 0.002 LDL-TG (mg/dl) 29.84±10.44 31.61±11.86 35.62±13.70 <0.001 LDL-C/LDL-TG 4.04(3.21-5.04) 3.83(3.06-4.84) 3.14(2.58-3.99) <0.001 HDL-C (mg/dl) 39.1±10.7 39.0±10.8 36.8±11.0 <0.001 HDL-TG (mg/dl) 14.55±6.51 16.15±6.90 18.49±7.68 <0.001 HDL-C/HDL-TG 2.88(2.08-3.82) 2.55(1.93-3.40) 2.09(1.52-2.78) <0.001 TG (mg/dl) 144(107-200) 145(107-198) 159(118-209) 0.005 ApoC3 (mg/dl) 14.44±5.36 14.34±4.71 15.30±5.37 0.001 LDL radius (nm) 8.25±0.21 8.29±0.22 8.33±0.24 <0.001 . G1: eGFR≥90 ml/min/1.73m2 . G2: eGFR 60-89 ml/min/1.73m2 . G3: eGFR≤60 ml/min/1.73m2 . P . LDL-C (mg/dl) 117.3±35.2 117.4±33.6 111.3±34.2 0.002 LDL-TG (mg/dl) 29.84±10.44 31.61±11.86 35.62±13.70 <0.001 LDL-C/LDL-TG 4.04(3.21-5.04) 3.83(3.06-4.84) 3.14(2.58-3.99) <0.001 HDL-C (mg/dl) 39.1±10.7 39.0±10.8 36.8±11.0 <0.001 HDL-TG (mg/dl) 14.55±6.51 16.15±6.90 18.49±7.68 <0.001 HDL-C/HDL-TG 2.88(2.08-3.82) 2.55(1.93-3.40) 2.09(1.52-2.78) <0.001 TG (mg/dl) 144(107-200) 145(107-198) 159(118-209) 0.005 ApoC3 (mg/dl) 14.44±5.36 14.34±4.71 15.30±5.37 0.001 LDL radius (nm) 8.25±0.21 8.29±0.22 8.33±0.24 <0.001 SP255A QUANTITATIVE ANALYSIS OF AORTIC CALCIFICATION IN PREDIALYSIS CKD PATIENTS BY USE OF AGATSTON SCORE Mitsuru Ichii Mitsuru Ichii 1 Osaka City University Graduate School of Medicine, Osaka, Japan Eiji Ishimura Eiji Ishimura 1 Osaka City University Graduate School of Medicine, Osaka, Japan Hideaki Shima Hideaki Shima 2 Ohno Memorial Hospital, Osaka, Japan Yoshiteru Ohno Yoshiteru Ohno 1 Osaka City University Graduate School of Medicine, Osaka, Japan Akihiro Tsuda Akihiro Tsuda 1 Osaka City University Graduate School of Medicine, Osaka, Japan Shinya Nakatani Shinya Nakatani 1 Osaka City University Graduate School of Medicine, Osaka, Japan Akinobu Ochi Akinobu Ochi 1 Osaka City University Graduate School of Medicine, Osaka, Japan Katsuhito Mori Katsuhito Mori 1 Osaka City University Graduate School of Medicine, Osaka, Japan Masaaki Inaba Masaaki Inaba 1 Osaka City University Graduate School of Medicine, Osaka, Japan Abstract Introduction and Aims: Vascular calcification is common and progressive in chronic kidney disease, and vascular calcification increases the risk of cardiovascular events. However, in CKD patients, the extent to which vascular calcification is advanced with regards to the progression of renal failure remains to be further elucidated. The aim of the present study was to quantitatively examine factors associated with aortic calcification in predialysis CKD patients. Methods: We quantitatively investigated presence or degree of aortic calcification in 149 predialysis CKD patients (58±16 years; 96 males and 53 females, 48 diabetics; eGFR 40.3±29.3 ml/min), and measured Agatston scores using a 64-slice CT scanner (Somatom Sensation 64; Siemens Medical Solutions, Forchheim, Germany), in which images were obtained with a 3 mm single slice thickness. The aorta distal to the renal artery to the bifurcation was examined. Aortic calcification was defined as the volume of 2 adjacent pixels with a CT density of > 130 Hounsfield units within the distribution of the abdominal aorta. Results: Of 149 patients, aortic calcification was present in 117, and absent in 32. In patients with aortic calcification, age (p<0.001), C-reactive protein (p<0.001), and intact-PTH (p < 0.001) were significantly higher, estimated glomerular filtration rate (eGFR) was significantly lower (p<0.001), and diabetes was observed more often (p<0.05). In regards to the degree of aortic calcification, the Agatston scores correlated significantly and positively with age (ρ=0.438, p<0.001) and serum phosphate (ρ=0.208, p=0.024), and correlated significantly but negatively with e-GFR (ρ=-0.353, p<0.001). Agatston scores increased according with advances in the CKD stages. In multiple regression analysis, eGFR and serum phosphate were associated significantly with log [Agatston score] (β = - 0.261, p = 0.003; β = 0.147, p = 0.046, respectively) after the adjustment of several confounders (R2 = 0.333, p < 0.001; R2 = 0.295, p < 0.001, respectively). However, log [intact PTH] was not associated with log [Agatston score] after the adjustment. eGFR was associated significantly and independently with the log [Agatston score] (β=-0.346, p<0.01), after adjustment for several confounders including age, gender, diabetes mellitus, hypertension, log [CRP], smoking, serum phosphate, and log [intact-PTH] (R2 = 0.301, p < 0.001). Conclusions: Hyperphospatemia, chronic inflammation, diabetes, and decreased GFR are associated significantly with the presence of aortic calcification in predialysis CKD patients. Decreased eGFR was associated significantly and independently with advancement of the quantitative degree of aortic calcification. SP256EFFICACY AND SAFETY OF ORAL FEBUXOSTAT COMPARED TO ALLOPURINOL IN SUBJECTS WITH MODERATE-TO-SEVERE CHRONIC KIDNEY DISEASE Vassilis Filiopoulos Vassilis Filiopoulos 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Nikolaos Manolios Nikolaos Manolios 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Dimitrios Hadjiyannakos Dimitrios Hadjiyannakos 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Dimitrios Arvanitis Dimitrios Arvanitis 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Ioannis Karatzas Ioannis Karatzas 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Dimosthenis Vlassopoulos Dimosthenis Vlassopoulos 1 "Sismanogleion-Amalia Fleming" General Hospital, Athens, Greece Abstract Introduction and Aims: Hyperuricemia is highly prevalent in patients with chronic kidney disease (CKD) and may contribute to renal disease progression. Therefore, uric acid-lowering therapy appears beneficial. Allopurinol has been associated with increased risk of toxicity in CKD. Febuxostat, a novel non-purine selective xanthine oxidase inhibitor, is an alternative to allopurinol in management of chronic hyperuricemia. However, insufficient safety and efficacy data are available for Febuxostat administration to subjects with impaired renal function. This study evaluated efficacy and safety of oral Febuxostat compared to allopurinol in subjects with stages 3-4 CKD. Methods: Thirty-eight patients, male/female 24/14, median age 70 (41-86) years with serum uric acid (sUA)≥8.0 mg/dl and serum creatinine (sCr)≥2.0 mg/dl received Febuxostat for one year. Febuxostat starting dose was 80 mg orally every other day with Cockcroft-Gault formula creatinine clearance eCrCl C-G) ≥ 30 ml/min and every third day with < 30 ml/min. This dose was adjusted to achieve sUA levels of ≤ 6 mg/dl. A well-matched group of 17 patients, male/female 10/7, age 72 (35-86), received allopurinol for one year. Allopurinol starting dose was 100 mg daily and increased gradually up to 300 mg. Patients with transplantation, active liver disease, or life threatening medical condition were excluded in both groups. Hematology, biochemistry blood tests and creatinine clearance with 24-hr urine collection (24hr-CrCl) were performed. eCrCl C-G as well as eGFR MDRD4 were calculated at baseline and every other month thereafter. Adverse events were recorded. Results: Baseline characteristics were similar in both groups, with the exception of sUA that was significantly higher in Febuxostat group (9.9±1.5 vs. 8.9±0.8 mg/dl, p=0.009). An equivalent reduction in sUA levels was found in both groups already by month 2 of the study (6.0±1.3 in Febuxostat vs. 6.2±1.2 mg/dl in Allopurinol group) and was maintained throughout the study with stable, within target sUA levels up to month 12 (5.5±0.6 vs. 5.7±0.7 mg/dl). Target sUA at month 12 was achieved in 33/38 (86.8%) patients in Febuxostat and 15/17 (88.2%) in Allopurinol group. Renal function, assessed by sCr, 24hr-CrCl, eGFR C-G and eGFR MDRD4, was stable or improved in both groups: baseline vs. month 12: 2.4±0.8 vs. 2.3±1.0 mg/dl; 31.3±13.1 vs. 33.4±16.0 ml/min; 31.9±12.7 vs. 34.8±14.8 ml/min, p=0.02; and 29.1±10.7 vs. 31.6±13.0 ml/min/1.73m2, respectively, significant only in eGFR C-G changes, in Febuxostat group and 2.2±0.6 vs. 2.1±1.3 mg/dl; 35.6±5.1 vs. 44.7±13.6 ml/min, p=0.02; 33.2±5.3 vs. 37.7±8.9 ml/min, p=0.04; and 33.2±4.7 vs. 38.4±8.8 ml/min/1.73m2, p=0.01, respectively, in Allopurinol group). 24hr-CrCl at month 12 was higher in Allopurinol group (p=0.01), with a trend, although non-significant, towards better sCr, eGFR C-G and MDRD4, as well. No significant differences were observed for the rest of studied parameters, including proteinuria and liver tests both between and within groups. Mild gastrointestinal adverse events were recorded in 5/38 (13.1%) patients of Febuxostat group, whereas none was reported in Allopurinol group. Conclusions: Febuxostat, administered over one-year appears to be comparable to allopurinol in terms of uric acid-lowering effect and safety with minimal side effects in management of chronic hyperuricemia for patients with moderate-to-severe CKD. Renal function improved in both groups, significantly in most parameters of Allopurinol group and less consistently in Febuxostat group. SP257PA21 DOES NOT INTERACT WITH ORAL VITAMIN D RECEPTOR AGONISTS: A POST HOC ANALYSIS OF A PHASE 3 STUDY Jürgen Floege Jürgen Floege 1 RWTH University Hospital Aachen, Aachen, Germany Jaco Botha Jaco Botha 2 Vifor Pharma, Glattbrugg, Switzerland Edward Chong Edward Chong 2 Vifor Pharma, Glattbrugg, Switzerland Stuart M Sprague Stuart M Sprague 3 Northshore University Health System University of Chicago Pritzker School of Medicine, Evanston, IL Abstract Introduction and Aims: Concomitant oral administration of phosphate binders with vitamin D analogues may result in drug-drug interactions, reducing the therapeutic activity of vitamin D receptor agonists (VDRAs). The impact of PA21 - a new iron-based phosphate binder (polynuclear iron(III)-oxyhydroxide) - on oral VDRAs was investigated in dialysis patients using serum iPTH concentrations as an efficacy marker. Methods: 1,059 patients were randomized to PA21 1.0-3.0 g/day (N=710) or sevelamer carbonate (SEV) 2.4-14.4 g/day (N=349) for a 12-week dose titration, followed by 12 weeks maintenance. Eligible patients were enrolled in a 28-week safety extension study. Three populations of PA21 and SEV-treated patients were analysed post hoc: Population (Pop.) 1 (PA21: n=139; SEV: n=72), patients taking concomitant stable doses of oral VDRAs, with no intravenous (iv) VDRA or cinacalcet; Pop. 2 (PA21: n=173; SEV: n=75), patients taking no concomitant VDRA or cinacalcet; and Pop. 3 (PA21: n=52; SEV: n=14), patients taking concomitant stable doses of iv VDRA (paricalcitol) only. Populations were compared using a mixed effects model to obtain the least squared (LS) mean change in iPTH from baseline to endpoint, and also differences between treatment groups. Results: Across all populations in the analysis, mean ± SD iPTH at baseline varied from 32±28 pmol/L to 47±26 pmol/L. In PA21-treated patients, serum iPTH concentrations decreased by 2.7 pmol/L from baseline to endpoint in Pop. 1 and increased by 5.7 pmol/L in Pop. 2 (P=0.024, Pop. 1 vs Pop. 2; Table). In Pop.3, iPTH decreased by 3.8 pmol/L in PA21-treated patients (P=0.87, Pop. 1 vs Pop. 3). In SEV-treated patients, iPTH increased from baseline to endpoint by 11.1 pmol/L and 6.2 pmol/L in Pop. 1 and Pop. 2, respectively (P=0.39, Pop. 1 vs Pop. 2; Table), and decreased by 1.2 pmol/L in Pop. 3 (P=0.32, Pop. 1 vs Pop. 3). There was a statistically significant difference between treatment groups in Pop. 1 (P=0.010). Conclusions: In PA21-treated patients, iPTH increased in Pop. 2 (no VDRAs), but decreased in Pop. 1 (oral VDRAs), with a similar decrease in Pop. 3 (iv VDRA). Opposite effects were seen in SEV-treated patients who received stable oral VDRAs (Pop. 1), which is consistent with its known pharmacokinetic interaction with oral calcitriol (Pierce D, et al. NDT 2011;26:1615-21). Together, these results indicate no interaction between PA21 and oral VDRAs. Open in new tabDownload slide Open in new tabDownload slide SP258SAFETY AND EFFICACY OF EVEROLIMUS GIVEN AT 10 MG/DAY IN ADVANCED RENAL CELL CARCINOMA (RCC) PATIENTS WITH STAGE III TO V CHRONIC KIDNEY DISEASE (CKD) Laura Cosmai Laura Cosmai 1 Istituti Ospitalieri Cremona, Cremona, Italy Camillo Porta Camillo Porta 2 IRCCS San Matteo University Hospital Foundation, Pavia, Italy Marina Foramitti Marina Foramitti 1 Istituti Ospitalieri Cremona, Cremona, Italy Cristina Masini Cristina Masini 3 University of Modena and Reggio Emilia, Modena, Italy Roberto Sabbatini Roberto Sabbatini 3 University of Modena and Reggio Emilia, Modena, Italy Fabio Malberti Fabio Malberti 4 Istituti Ospitalieri Cremona, Creamona, Italy Abstract Introduction and Aims: Everolimus is commonly used as an immunosuppressant in renal transplant recipients; most recently, it was also registered for the treatment of advanced RCC patients pre-treated with tyrosine kinase inhibitors. The two indications are very different, especially when it relates to the dose, almost 5 times higher in patients with metastatic RCC (10 mg/day). Data on safety and efficacy of Everolimus in patients with RCC (usually nephrectomized) and concomitant CKD are limited by the extremely restrictive selection criteria used in the pivotal RECORD-1 trial Methods: We retrospectively evaluated the trend of renal function, electrolytes, proteins and fat values (before initiation of therapy, and then at 3 and 5 months) in 40 patients with advanced RCC and different stages of CKD treated with Everolimus. We also correlated this trend with Everolimus tolerability profile, as well as antitumor efficacy parameters, such as Disease Control Rate (DCR) and Progression-Free Survival (PFS). Furthermore, toxicity has been evaluated in accordance with the Common Toxicity Criteria of the National Cancer Institute (NCI-CTC), Version 3.0 Results: Only 4 patients with stage III CKD at the beginning of treatment showed a worsening of renal function under treatment with Everolimus (already evident at 3 months), without the need to discontinue or temporarily interrupt treatment; however, in two of them, Everolimus was dose-reduced to 5 mg/day for acute renal toxicity (AKI). Furthermore, there was no evidence of significant electrolyte disturbances, while alterations in glucose and lipid metabolism, as well as a decline in hemoglobin (consistent with the known toxicity profile) were observed. Conclusions: Everolimus proved to be active and safe also in RCC patients with concomitant stage III to V CKD SP259PREVALENCE, CAUSES AND RISK FACTOR FOR HYPOMAGNESAEMIA IN NON-DIALYSIS CKD PATIENTS Usama Elewa Usama Elewa 1 IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain Dimitra Nastou Dimitra Nastou 1 IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain Beatriz Fernández Beatriz Fernández 1 IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain Jesus Egido Jesus Egido 1 IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain Alberto Ortiz Alberto Ortiz 1 IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain Abstract Introduction and Aims:CKD patients were thought to have hypomagnesaemia. However, hypomagnesaemia is frequent among diabetics and guidelines recommend magnesium supplementation in diabetics since low magnesium levels are associated with adverse outcomes. Diuretics and protein pump inhibitors are frequently used in CKD patients and are associated with hypomagnesaemia.To define the prevalence, potential causes and risk factor for hypomagnesaemia in CKD. Methods:A Retrospective study of a cohort of 351 CKD outpatients in a tertiary care hospital center have been included using an electronic database. The prevalence of hypomagnesaemia (s. Mg <1.7 mg/dl), cause (renal vs. non renal) and potential risk factors were investigated. Results:60 patients (17%) were hypomagnesaemic and 87 (24%) were hypomagnesaemic (Table 1). Prevalence of hypomagnesaemia per CKD stage is shown in table 2. The highest serum magnesium level was 3.02 mg/dl (within a safe range). The low magnesium group differed from the high magnesium group in age, eGFR, fractional excretion of magnesium (FEMg) and PTH (Table 1). In a univariate analysis magnesium levels correlated with age (p 0.0001), phosphate (p 0.0006), PTH (p 0.0001), and non-calcium binders (p 0.0001), 1-25 hydroxyvitamin D or paricalcitol (p 0.0001), and inversely with eGFR (p 0.0001) and oral magnesium (p 0.001). In a multivariate analysis (R2 0.18) magnesium levels correlated with age (p 0.0008), phosphate (p 0.0011), and inversely with eGFR (p 0.0062) and PTH (p 0.0045). Among the low serum magnesium patients, 53 (88.3%) had a FEMg >2%, suggestive of renal magnesium losses. Conclusions:1.Hypomagnesaemia is relatively frequent in CKD patients. There is an evidence for a contribution of renal magnesium losses.2.Age, hyperparathyroidism, hyperphosphatemia and kidney disease were independent predictors of serum magnesium. We postulate that CKD patients with low magnesium levels may specially benefit from magnesium-containing phosphate binders. Open in new tabDownload slide Open in new tabDownload slide Open in new tabDownload slide Open in new tabDownload slide SP260EX VIVO SUPPRESED ACTIVITY OF SERUM FROM CHRONIC KIDNEY DISEASE (CKD) PATIENTS ON MACROPHAGE FOAM CELL FORMATION IS RELATED TO ESTIMATED GLOMERULAR FILTRATION RATE (eGFR) PRESERVATION BY OLMESARTAN ADMINISTRATION Shigeko Hara Shigeko Hara 1 Toranomon Hospital, Tokyo, Japan 2 Hara Press Center Clinic, Tokyo, Japan Kentaro Tanaka Kentaro Tanaka 3 The Division of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan Akifumi Kushiyama Akifumi Kushiyama 3 The Division of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan Ken Sakai Ken Sakai 4 Department of Nephrology, School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan Naoki Sawa Naoki Sawa 5 Kidney Center,Toranomon Hospital, Tokyo, Japan Junichi Hoshino Junichi Hoshino 5 Kidney Center,Toranomon Hospital, Tokyo, Japan Yoshifumi Ubara Yoshifumi Ubara 6 Kidney Center, Toranomon Hospital, Tokyo, Japan Kenmei Takaichi Kenmei Takaichi 6 Kidney Center, Toranomon Hospital, Tokyo, Japan Abstract Introduction and Aims: During progression of CKD, inflammation have been reportedly associated. In inflammatory process, macrophages are differentiated into cytokine-secreting foam cells. Angiotensin receptor blocker (ARB) is thought to act as not only anti-hypertension but also anti-inflammation. There is no way to evaluate systemic or renal inflammatory state involved in the serum ability of macrophage activation. Therefore we developed novel bioassay, the ex vivo assay of macrophage foam cell formation using serum from CKD patients, and investigated whether progression of CKD and the effect of Olmesartan administration is related to serum activity in inducing foam cell formation. Methods: The subjects are 32 CKD patients (mean age 59.1 years, male 21: female 11). The laboratory data and clinical findings of patients were checked and at the same time, sera were collected at the start and 3- month during the period of Olmesartan treatment. As the laboratory data, blood pressure (systolic,diastolic), serum creatinine, eGFR, urine protein (gCreatinine ratio) and urine L-FABP ( gCreatinine ratio) were checked. eGFR value was calculated by Japanese formula. The measurement of serum activity inducing ex vivo macrophage differentiation is performed as follows: 2% serum from CKD patients were added to J774.1 cells and the degree of foam cell induction was quantified by measuring lipid accumulation. The values were adjusted for the number of the cells quantified by staining nuclei. These values were standardized on activity obtained from dilution series of VLDL. The value is termed as the MMI (Macrophage Maturation Index), 1 MMI stands for the same ability to form foam cell as 10μg/ml VLDL. During the 3-month treatment period, whether MMI change (ΔMMI) by Olmesartan administration was involved in eGFR change (ΔeGFR) was investigated. The data are expressed as mean ± standard deviation (SD). The differences between two groups were assessed using unpaired Student’s t-tests. Multiple linear regression analyses were performed for the association between ΔMMI and ΔeGFR or other parameters. p values <0.05 is defined as statistically significant. Results: At the start and 3-month of Olmesartan treatment, clinical findings and laboratory data were as follows; systolic blood pressure (130±8mmHg at the start, 125±18,at3month p=0.09), urine protein (1.48±1.08g/urine gCr, 1.24±1.06 , p=0.003), and eGFR (44.5±28.7mL/min/1.73m2, 42.3±26.7 , p=0.004) were decreased. In MMI decreased group (15cases), ΔeGFR was 0.09±2.51 ml/min/1.73m2, and ΔeGFR was -4.19±6.53 ml/min/1.73m2in MMI increased group (17cases) with significant difference (p=0.023). The negative association between ΔMMI and ΔeGFR was shown by univariate regression model analysis, and the formula for the association was ΔeGFR = -0.285 × ΔMMI -2.355 (p<0.0001). The association was independent of ΔBP, the effect of Olmesartan treatment on blood pressure. Moreover, the association remained significant(P=0.0004) after adjusted for age, sex, ΔBP, and ΔUrine protein. Conclusions: ARB Olmesartan is suggested to be related to improvement of renal function via anti-inflammatory mechanism. Serum activity for macrophage foam cell formation plays important roles in progression of CKD independently of blood pressure. SP261COCKCROFT&GAULT AND CKD-EPI EQUATIONS: ARE THESE EQUATIONS CONCORDANT TO ADJUST DRUG DOSAGE? Antoine Bouquegneau Antoine Bouquegneau 1 Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium Emmanuelle Vidal-Petiot Emmanuelle Vidal-Petiot 2 Department of Renal Physiology, Hôpital Bichat, AP-HP and Denis Diderot University, Paris, France François Vrtovsnik François Vrtovsnik 2 Department of Renal Physiology, Hôpital Bichat, AP-HP and Denis Diderot University, Paris, France Etienne Cavalier Etienne Cavalier 3 Department of Clinical Chemistry, University of Liège, Chu Sart Tilman, Liège, Belgium Jean Marie Krzesinski Jean Marie Krzesinski 1 Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium Martin Flamant Martin Flamant 2 Department of Renal Physiology, Hôpital Bichat, AP-HP and Denis Diderot University, Paris, France Pierre Delanaye Pierre Delanaye 1 Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium Abstract Introduction and Aims: When obese patients are considered, one important issue is the question of body surface area (BSA) indexation. In Pharmacology, the Cockcroft&Gault (CG) equation is still recommended to adapt drug dosage. In Nephrology, KDIGO recommend using CKD-EPI equation to estimate glomerular filtration rate (eGFR) and to “deindex” the equation to adjust drugs. Both in Pharmacology and Nephrology, the variable “weight” matters in the context of obesity. Therefore, adjusted ideal body weight (AIBW) is sometimes preferred to actual body weight in these patients. In this study, we test the concordance of the different equations to adjust drug dosage. Methods: Patients with body mass index (BMI) higher than 30 kg/m² were included. We calculate AIBW as followed: Ideal Body Weight + (0.4 *(Actual Body Weight - Ideal Body Weight)). In this work, we will compare results obtained with CKD-EPI, using the “deindexed” value, as recommended (calculated by multiplying eGFR by each individual’s body surface area and by dividing this intermediate result by 1.73 m2). CG and CGAIBW are non-indexed and also expressed in mL/min. We calculated bias (defined as the mean difference between CKD-EPIdeindexed and CGs), precision (defined as the SD around the bias) and accuracy 30% (defined as the percentage of CKD-EPIdeindexed within ± 30% of CGs). All patients were then classified according to the level of GFR (stage 1: eGFR > 90, stage 2: eGFR 60-90, stage 3: eGFR 30-60 and stage 4: eGFR<30 mL/min). We then calculated the concordance in this classification between these equations. Results: The population included 366 patients (185 women) from two different areas. Mean age was 55 ± 14 years and mean BMI was 36 ± 7 kg/m2. Mean eGFR by CG and CGAIBW were 96 ± 64 and 73 ± 45 mL/min, respectively. Mean eGFR by CKD-EPI deindexed was 77 ± 44 mL/min. In the global population, when we considered CG and CKD-EPIdeindexed, mean bias was -18.8 ± 24.7 and accuracy 30% between the equations was 86%. When we used CGAIBW, mean bias was +3.6 ± 8.6 and accuracy 30% was 99% (p<0.0001). Regarding the classification of the patients, the concordance between CG and CKD-EPI deindexed versus between CGAIBW and between CKD-EPI deindexed was 79.2% and 84.9%, respectively (p=0.06). Conclusions: In the context of obesity, we observed a good concordance between the results given by the CG equation and CKD-EPIdeindexed if the AIBW is considered. Using actual weight induces discrepancies between the equations with potential consequences on drug dosage adjustment. Our study illustrates these potential discrepancies but it remained to be definitively proven that CKD-EPI deindexed (or CGAIBW) performs better than CG with actual weight for the adjustment of drug dosage in obese patients. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP262UREMIC PRURITUS IN CHILDREN Katarzyna Kilis-Pstrusinska Katarzyna Kilis-Pstrusinska 1 Wroclaw Medical University, Wroclaw, Poland Elzbieta Prus-Wojtowicz Elzbieta Prus-Wojtowicz 1 Wroclaw Medical University, Wroclaw, Poland Jacek C Szepietowski Jacek C Szepietowski 1 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction and Aims: Chronic kidney disease (CKD), regardless of its cause, may be accompanied by various skin lesions. The most common symptom in adults suffering from CKD is pruritus. The literature data on uraemic pruritus in children is very limited. The aim of this study was to evaluate the frequency and severity of pruritus and skin dryness in children with (CKD). Methods: The study included 103 children: 72 with CKD, stage 3-5 (mean age 11.0 ± 4.5 years, range: 4-17) and 31 patients with monosymptomatic primary nocturnal enuresis as a reference group (mean age 10.7 ± 3.9 years, range: 4-17). Among children with CKD there were 34 on dialysis (haemodialysis or peritoneal dialysis) and 38 treated conservatively.The pruritus was assessed using own survey, a questionnaire assessment of pruritus and a visual analogue scale. Skin dryness was assessed using several tools. Initially the study subjects described the site and severity of this symptom (mild, moderate, severe) themselves. Next, clinical evaluation of skin dryness, non-invasive corneometric assessment of epidermis moisturizing and measurement of transepidermal water loss using tewameter were performed. Results: Pruritus in children with CKD was found in 20.8% of cases. In the group of patients treated conservatively pruritus was observed in 18.4% of patients, and among dialysis in 23.5% (p=0.02). Xerosis was more commonly found in children with pruritus (66.7%) compared to those without pruritus (50.9%) (p<0.01). Xerosis was more severe in children with pruritus than without pruritus. The problem of dry skin was identified more frequently in patients on dialysis (67.6%) than conservative treatment (42.1%) (p<0.01). Conclusions: Dry skin is a major concern of children with CKD, intensifying as the disease progresses. Dry skin may play an important role in pathogenesis of pruritus in children with CKD, which is shown by higher incidence of dry skin and a greater severity in children with pruritus compared to those without pruritus. SP263INFLAMMATION IS A NOVEL RISK FACTOR FOR ATRIAL FIBRILLATION IN CHRONIC KIDNEY DISEASE Dominic S Raj Dominic S Raj 1 George Washington University, Washington, DC Richard Amdur Richard Amdur 2 MFA-George Washington University, Washington, DC Cric Study Investigators Cric Study Investigators Abstract Introduction and Aims: To determine the association between inflammation and risk for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Methods: AF was determined by self-report and electrocardiogram in 3,762 Chronic Renal Insufficiency Cohort study participants. Plasma concentrations of IL-1β, IL-receptor antagonist, IL-6, IL-10, TNF-α, TGF-β, hs-CRP and fibrinogen were measured at baseline visit. Predictors of incident and prevalent AF were examined using multivariable-adjusted logistic regression. Results: At baseline visit 642 subjects were determined to have AF. During a mean follow-up of 3.7 years, 246 patients had either continuing (n=138) or new-onset AF (n=108). The odds for AF at baseline visit was higher with calcium channel blocker use (4.09 [95% CI 1.51, 11.11], p=0.006), larger left atrial (LA) diameter (7.74 [95% CI 3.73, 16.05], p<0.001) and elevated plasma interleukin (IL)-6 (1.84 [95% CI 1.15-2.93], p=0.01), but lower with black race (0.27 [95% CI 0.09, 0.80], p=0.02). Odds for new-onset or continuing AF was higher in subjects within the highest tertiles of IL-6 (3.42 ([95% CI 95% CI 2.39, 4.89], p<0.001) and hs-CRP (2.08 [95% CI 1.50, 2.88], p<0.001), but lower for the highest IL-10 tertile (0.62 [95% CI 0.46-0.85], p=0.022). Each 1-unit increase in log (IL-6) and log (IL-1β) were independently associated with 40% increase and 38% decrease in risk for new-onset AF, respectively. Conclusions: Elevated IL-6 is an independent predictor of prevalent as well as new onset AF in CKD patients. SP264EXAMINATION ABOUT SERUM BICARBONATE LEVELS AND SODIUM BICARBONATE AT DIALYSIS INITIATION Junichiro Yamamoto Junichiro Yamamoto 1 Tsushima City Hospital, Tsushima, Japan 2 AICOPP Study Group, Nagoya, Japan Masayoshi Mori Masayoshi Mori 1 Tsushima City Hospital, Tsushima, Japan Naoya Sugiyama Naoya Sugiyama 1 Tsushima City Hospital, Tsushima, Japan Daijo Inaguma Daijo Inaguma 2 AICOPP Study Group, Nagoya, Japan Abstract Introduction and Aims: It has been reported that correction of metabolic acidosis is important goal in chronic kidney disease (CKD). However, the correction of serum bicarbonate levels has not yet been identified. The aim of this study was to examination about serum bicarbonate levels and sodium bicarbonate (NaHCO3) at dialysis initiation. Methods: This study, named AICOPP study (Aichi cohort study of prognosis in patients newly initiated into dialysis), included 1527 patients who began dialysis therapy between October 1, 2011 and September 30, 2013 at 17 dialysis centers in Aichi, Japan.1116 patients (mean age,67.16±13.04 years; male 763, female 353) were screened by serum bicarbonate (HCO3-) levels. The entire HCO3- (mmol/L) range was divided into 4 group(group 1: <17, group 2: 17~19.9, group 3: 20~24.9, group 4: ≧25) and NaHCO3 oral administration group (Bicarbonate+) or without oral administration group (Bicarbonate-). Vales were compared by unpaired t-test or post hoc test. Results: The underlying disease had most diabetic nephropathy. The nephrologists follow-up period, estimated GFR (eGFR) level at dialysis initiation, rate of decline of renal function, BNP level at dialysis initiation did not show the significant difference at the group interval of HCO3- levels. The nephrologists follow-up period was longer Bicarbonate+ group compared with Bicarbonate- group. The eGFR levels at dialysis initiation was significantly lower Bicarbonate+ group compared with Bicarbonate- group (5.049 < 5.641 ml/min/1.73m2). The rate of decline of renal function was significantly slower Bicarbonate+ group compared with Bicarbonate- group (0.737 < 2.230 ml/min/1.73m2/month),and Bicarbonate- group was significantly faster than Bicarbonate+ group in ARB oral administration group (0.637 < 2.677 ml/min/1.73m2/month). Furthermore, Bicarbonate+ group was later than Bicarbonate- group in uric acid synthetic inhibitor oral administration group (0.611 < 1.974 ml/min/1.73m2/month). The BNP level at dialysis initiation was lower Bicarbonate+ group compared with Bicarbonate- group (490.26 < 619.46 pg/ml). Cardiothoracic ratio, LVEF, serum albumin were did not show the significant difference at the group interval of HCO3- levels, and, in Bicarbonate+ group and Bicarbonate- group. Serum potassium levels showed a steady range as the group which was high in HCO3- levels. Conclusions: These results of this study suggest that NaHCO3 oral administration don’t cause the cardiac load and has a beneficial effect on renal function. SP265TH1 AND TH2 IN ATOPIC CHILDREN WITH NEPHROTIC SYNDROME Doaa M Youssef Doaa M Youssef 1 Zagazig University, Cairo, Egypt Amal A Alshal Amal A Alshal 2 Zagazig University, Zagazig, Egypt Rabab M Elbehidy Rabab M Elbehidy 2 Zagazig University, Zagazig, Egypt Abstract Introduction and Aims: Many studies have described a higher incidence of allergic disorders in children with steroid-responsive nephrotic syndrome, as immunological studies in these children have been somewhat variable.in this study we tried to find relation between Th1 activity and Th2 activity both in activity and in remission in atopic versus non-atopic children with steroid sensitive nephrotic syndrome (SSNS). Methods: a case-control study was done; We tested two groups; group I 42 children (24 males and 18 females) with SSNS, Group II 50 healthy children (24 males and 26 females) acting as control group with age ranged from 4 to 11 years old. Group I subdivided into group I a (17) children with atopy and group I b (25) non-atopic. Patients were tested in activity and after remissionAtopy was diagnosed on the basis of positive family history, Clinical parameters of atopy, namely asthma, eczema, recurrent urticaria and allergic rhinitis, and serum IgE concentration. All the patients were subjected to complete history taking, thorough clinical examination, and routine investigations as protein in 24 hours urine, serum albumin, and complete blood count, IgE level measured Th1 activity by measuring level of IL2, TNF alpha and Th2 activity by measuring IL4, IL13 both in activity and in remission. Results: In patients group; we found that there was significant higher level of markers of Th1(TNFα) and Th2( IL4,IL13 and IgE) over control during activity, while in remission there levels goes to lower levels but still higher than levels of control.In activity; by comparing both atopic and non-atopic children we found there were significant higher levels of markers of Th2 in atopic than in non-atopic patients, while there were none significant difference between atopic and non-atopic as regard markers of Th1.In remission; there was no significant difference between levels of markers of Th1 and Th2 between patients who were atopic and non-atopic with nephrotic syndrome. Conclusions: We concluded that in atopic children with nephrotic syndrome both Th1 and Th2 play roles in initiating the disease, but we can suspect a more active role of Th2 especially in activity than after remission comparison between atopic children and non-atopic ones in activity and in remission . Atopic patients In activity . Non-atopic patients In activity . p . Atopic patients in remission . Non-atopic patients in remission . p . Age 5.4±2 6.12±2 0.324 Serum albumin 1.7±0.65 1.9±0.77 0.585 3.8±0.49 4±0.26 0.137 TNFα (ng/mL) 2.85±0.4 (2.1-3.5) 2.9±0.37 (2-3.5) 0.628 1.14±0.23 (0.8-1.5) 1.2±0.26 (0.8-1.6) 0.375 IL2 (ng/mL) 2.8±1 (1.3-4.1) 2.9±0.9 (1.6-5) 0.77 2.95±0.52 (1.53-3) 2.73±.66 (1.3-4.2) 0.227 IgE (IU/ml) 251.9±65.8 (13-340) 141.6±62.5 (70-200) 0.000 99.2±22.9 (50-143) 37.8±23 (18-67) 0.000 IL4 (pg/mL) 35.6±5.9 (28-45) 19.2±4.2 (6-37.2) 0.000 8.4±2.2 (6.5-15) 8.1±2.77 (4.1-14) 0.746 IL13 (pg/mL) 107.76±31.7 (50-173) 66.5±35 (28-67) 0.000 17.54±3.8 (10-23) 15.3±3.87 (9-21) 0.075 . Atopic patients In activity . Non-atopic patients In activity . p . Atopic patients in remission . Non-atopic patients in remission . p . Age 5.4±2 6.12±2 0.324 Serum albumin 1.7±0.65 1.9±0.77 0.585 3.8±0.49 4±0.26 0.137 TNFα (ng/mL) 2.85±0.4 (2.1-3.5) 2.9±0.37 (2-3.5) 0.628 1.14±0.23 (0.8-1.5) 1.2±0.26 (0.8-1.6) 0.375 IL2 (ng/mL) 2.8±1 (1.3-4.1) 2.9±0.9 (1.6-5) 0.77 2.95±0.52 (1.53-3) 2.73±.66 (1.3-4.2) 0.227 IgE (IU/ml) 251.9±65.8 (13-340) 141.6±62.5 (70-200) 0.000 99.2±22.9 (50-143) 37.8±23 (18-67) 0.000 IL4 (pg/mL) 35.6±5.9 (28-45) 19.2±4.2 (6-37.2) 0.000 8.4±2.2 (6.5-15) 8.1±2.77 (4.1-14) 0.746 IL13 (pg/mL) 107.76±31.7 (50-173) 66.5±35 (28-67) 0.000 17.54±3.8 (10-23) 15.3±3.87 (9-21) 0.075 comparison between atopic children and non-atopic ones in activity and in remission . Atopic patients In activity . Non-atopic patients In activity . p . Atopic patients in remission . Non-atopic patients in remission . p . Age 5.4±2 6.12±2 0.324 Serum albumin 1.7±0.65 1.9±0.77 0.585 3.8±0.49 4±0.26 0.137 TNFα (ng/mL) 2.85±0.4 (2.1-3.5) 2.9±0.37 (2-3.5) 0.628 1.14±0.23 (0.8-1.5) 1.2±0.26 (0.8-1.6) 0.375 IL2 (ng/mL) 2.8±1 (1.3-4.1) 2.9±0.9 (1.6-5) 0.77 2.95±0.52 (1.53-3) 2.73±.66 (1.3-4.2) 0.227 IgE (IU/ml) 251.9±65.8 (13-340) 141.6±62.5 (70-200) 0.000 99.2±22.9 (50-143) 37.8±23 (18-67) 0.000 IL4 (pg/mL) 35.6±5.9 (28-45) 19.2±4.2 (6-37.2) 0.000 8.4±2.2 (6.5-15) 8.1±2.77 (4.1-14) 0.746 IL13 (pg/mL) 107.76±31.7 (50-173) 66.5±35 (28-67) 0.000 17.54±3.8 (10-23) 15.3±3.87 (9-21) 0.075 . Atopic patients In activity . Non-atopic patients In activity . p . Atopic patients in remission . Non-atopic patients in remission . p . Age 5.4±2 6.12±2 0.324 Serum albumin 1.7±0.65 1.9±0.77 0.585 3.8±0.49 4±0.26 0.137 TNFα (ng/mL) 2.85±0.4 (2.1-3.5) 2.9±0.37 (2-3.5) 0.628 1.14±0.23 (0.8-1.5) 1.2±0.26 (0.8-1.6) 0.375 IL2 (ng/mL) 2.8±1 (1.3-4.1) 2.9±0.9 (1.6-5) 0.77 2.95±0.52 (1.53-3) 2.73±.66 (1.3-4.2) 0.227 IgE (IU/ml) 251.9±65.8 (13-340) 141.6±62.5 (70-200) 0.000 99.2±22.9 (50-143) 37.8±23 (18-67) 0.000 IL4 (pg/mL) 35.6±5.9 (28-45) 19.2±4.2 (6-37.2) 0.000 8.4±2.2 (6.5-15) 8.1±2.77 (4.1-14) 0.746 IL13 (pg/mL) 107.76±31.7 (50-173) 66.5±35 (28-67) 0.000 17.54±3.8 (10-23) 15.3±3.87 (9-21) 0.075 SP266EFFECT OF ALDOSTERONE ANTAGONISTS ON CKD PROGRESSION: A META-ANALYSIS Davide Bolignano Davide Bolignano 1 CNR-National Council of Research, Reggio Calabria, Italy Suetonia Palmer Suetonia Palmer 2 University of Otago, Christchurch, New Zealand Sankar Navaneethan Sankar Navaneethan 3 Glickman Urological and Kidney Institute, Cleveland, OH Giovanni Strippoli Giovanni Strippoli 4 University of Bari, Bari, Italy 5 Diaverum Medical Scientific Office, Lund, Sweden 6 Mario Negri Sud Consortium, Bari, Italy Abstract Introduction and Aims: Reducing proteinuria with ACEi or ARBs is the mainstay of treatment to retard progression of chronic kidney disease (CKD). Aldosterone antagonists (AAs) in addition to renin-angiotensin system (RAS) inhibition may provide additive benefits on proteinuria and further prevent progression of CKD. This updated systematic review and meta-analysis evaluates the benefits and harms of aldosterone antagonists alone or in combination with RAS inhibition in the setting of chronic kidney disease. Methods: We searched the Cochrane Renal Group's specialized register of trials to 30 January 2013 to identify randomized controlled trials (RCTs) and quasi-RCTs comparing AAs alone or in combination with ACEi and/or ARBs against other anti-hypertensive strategies or placebo. Data were summarized using random effects meta-analysis and summary treatment estimates were calculated as mean difference (MD) for continuous outcomes and risk ratio (RR) and number needed to harm (NNH) for dichotomous outcomes together with their 95% confidence intervals (CI). Results: Twenty-seven studies (comprising 1549 participants) were eligible for inclusion. Data on patient-focused outcomes, such as mortality and progression to ESKD, were sparse and scarce. Compared to ACEi and/or ARBs alone, non-selective AAs (spironolactone) combined with ACEi and/or ARB significantly reduced 24-hour protein excretion (11 studies, 596 patients; SMD -0.61 g/day, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure at the end of treatment with additional non-selective AA therapy (systolic BP: 10 studies, 556 patients; MD -3.44 mmHg, 95% CI -5.05 to -1.83; diastolic BP:9 studies, 520 patients; MD -1.73 mm Hg, 95% CI -2.83 to -0.62). However, AA treatment had inconclusive effects on the end of treatment GFR (9 studies, 528 patients; MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51) , doubled the risk of hyperkalemia (11 studies, 632 patients; RR 2.00, 95% CI 1.25 to 3.20; NNH: 7.2 ,95% CI 3.4 to ∞) and increased the risk of gynecomastia compared to ACEi and/or ARB alone (4 studies, 281 patients; RR 5.14, 95% CI 1.14 to 23.23; NNH: 14.1, 95% CI 8.7 to 37.3). The overall quality of the evidence was low. Most studies enrolled few patients and were powered to observe differences in surrogate end points only. Furthermore, the majority of studies did not adequately report study methods to assess methods and study quality. Conclusions: AAs reduce proteinuria and blood pressure but treatment effects on patient-relevant outcomes including progression to ESKD and major cardiovascular events are unknown and treatment hazards include hyperkalemia and gynecomastia. Further trials adequately powered to evaluate survival, cardiovascular events and progression of CKD are needed before widespread clinical use of AAs can be justified. SP267PREDICTORS OF HYPERKALEMIA RISK FOLLOWING HYPERTENSION CONTROL WITH ALDOSTERONE BLOCKADE ACCORDING TO THE PRESENCE OR ABSENCE OF CHRONIC KIDNEY DISEASE Ye Na Kim Ye Na Kim 1 Kosin University College of Medicine, Busan, Republic of Korea Kiryong Park Kiryong Park 2 Changwon Fatima Hospital, Changwon, Republic of Korea Sangeon Gwoo Sangeon Gwoo 1 Kosin University College of Medicine, Busan, Republic of Korea Ho Sik Shin Ho Sik Shin 1 Kosin University College of Medicine, Busan, Republic of Korea Yeon Soon Jung Yeon Soon Jung 1 Kosin University College of Medicine, Busan, Republic of Korea Hark Rim Hark Rim 1 Kosin University College of Medicine, Busan, Republic of Korea Hyun Yul Rhew Hyun Yul Rhew 1 Kosin University College of Medicine, Busan, Republic of Korea Abstract Introduction and Aims: Aldosterone antagonists have proven efficacy for management of hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses predictors of hyperkalemia risk following hypertension control with aldosterone blockade according to the presence or absence of chronic kidney disease Methods: Patients used in the analysis were seen between January 1, 2000 through November 30, 2012. 6575 patients with hypertension were evaluated for safety of aldosterone blockade added to preexisting BP-lowering regimens. Hyperkalemia was defined more than serum K 5.0 mEq/L.Patients were evaluated after 4 and 8 treatment weeks. Incidence of hyperkalemia, significant renal dysfunction (reduction eGFR ≥30%) and adverse effects according to the presence or absence of chronic kidney disease was assessed. Results: After 4 weeks of treatment, the incidence of hyperkalemia (serum K ≥ 5.0 mEq/L) according to the presence or absence of chronic kidney disease was 5.2%, 32.7% respectively. After 8 weeks of treatment, the portion of hyperkalemia (serum K ≥ 5.0 mEq/L) according to the presence or absence of chronic kidney disease was 0.5%, 2.6% respectively. In logistic regression for predicting hyperkalemia following aldosterone antagonism, predictors of hyperkalemia risk were old age, CKD, male, basal hyperkalemia and reduction in eGFR Conclusions: Spironolactone was well tolerated in selected patients with CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide Fig. 3 Open in new tabDownload slide Fig. 3 Open in new tabDownload slide Fig. 4 Open in new tabDownload slide Fig. 4 Open in new tabDownload slide SP268THE EVALUATION OF RED CELL DISTRIBUTION WIDTH IN CHRONIC HEMODIALYSIS PATIENTS Hikmet Tekce Hikmet Tekce 1 AIB University Hospital, Bolu, Turkey Buket Kin Tekce Buket Kin Tekce 2 Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey Gulali Aktas Gulali Aktas 2 Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey Abstract Introduction and Aims: Red cell distribution width (RDW), a parameter of routine blood count tests, usually used for differential diagnosis of anemia. However, recent studies pointed that RDW should be an independent predictor of mortality in general population and in some certain conditions but, the underlying physiopathological mechanism remained unclear. There is no data in literature about RDW levels independent from anemia and volume status and it’s association with clinical parameters. Therefore, we aimed to study RDW levels in hemodialysis (HD) patients without anemia and with sufficient iron storage and also studied the association between RDW and inflammatory, nutritional and volume markers. Methods: We retrospectively analysed 514 patients who received HD treatment between 2008-2012. We included stable HD patients with sufficient irone storage and without anemia or hypervolemia. After exlusion of the patients 296 remained for statistical analyse as study population. We grouped patients into 4 groups according to clinical parameters, albumin and C-reactive protein (CRP): Group 1 (n=92), no malnutrition or inflammation (albumin>3.5 g/dL and CRP<5 mg/dL); group 2 (n=81), inflammation alone (albümin>3.5 gr/dL and CRP>5 mg/dL); group 3 (n=74) malnutrition alone (albumin<3.5 gr/dL and CRP<5 mg/dL) and group 4 (n=49), both malnutrition and inflammation (albumin<3.5 gr/dL and CRP>5 mg/dL). Results: Mean RDW of all study population was 17.2% (reference range: 12-16%). The lowest RDW levels were found in group 1 (13.2%). Although RDW of group 2 were higher than group 1, it was still in normal range (14.7% vs 12.4%, p<0.01). RDW levels of group 3 (17.8%) and 4 (18.5%) significantly higher than groups 1 and 2 and above normal range. RDW levels were not significantly different in patients with and without hepatitis B and C. (16.7%, 16.2%, and 17.1%, p>0.05; respectively). Correlation analyse revealed a positive correlation between RDW and HD duration, interdialytic weight gain, serum phosphate and CRP levels and a negative correlation with serum albumin. HD duration, CRP, interdialytic weight gain and serum albumin have been found as independent predictors of RDW elevation in multivariate analyses. Conclusions: The results of present study reflects negative effects of inflammation, malnutrition and interdialytic excess weight gain on RDW elevation in a HD study cohort with sufficient iron storage and without anemia and hypervolemia. SP269INSIGHTS INTO DIALYSIS PATIENTS’ LIVES OFFER A NEW PERSPECTIVE FOR IMPROVING COMPLIANCE WITH PHOSPHATE BINDER THERAPY: LEARNINGS FROM AN ETHNOGRAPHIC STUDY Frank Schiepe Frank Schiepe 1 Vifor Pharma, Glattbrugg, Switzerland Yasmine Draz Yasmine Draz 1 Vifor Pharma, Glattbrugg, Switzerland Viatcheslav Rakov Viatcheslav Rakov 1 Vifor Pharma, Glattbrugg, Switzerland Abstract Introduction and Aims: Phosphate binders (PBs), used in the treatment of hyperphosphataemia, are orally self-administered. Several factors influence patient compliance to PB treatment, including their attitude to treatment, product attributes and socioeconomic factors. To better understand factors affecting compliance in general and, more specifically, compliance to PB treatment, an ethnographic study was undertaken. This included analysing the influence of stakeholders such as family members, peers and healthcare practitioners on patient compliance. Methods: This study included six patients with Stage 5 chronic kidney disease (CKD) from France, Germany, Italy, Spain and the UK. Interviews took place at patients’ homes over 4-6 hours. The aim was to explore how dialysis patients manage their disease on a daily basis. Interviewing patients in their homes allowed for greater understanding of their everyday routine and generated data on their attitude to CKD. Data obtained included audio and written transcripts of visits, a 7-day meal diary and photographs of their homes and medication. Data were analysed using descriptive statistics. Results: Data from 30 patients were available. This sample was representative of the overall patient population, in terms of demographics and socioeconomic background. Three patient types were identified. The ‘Afflicted’ type, comprising >50% of respondents, was characterised by a lack of structure and discipline that often led to non-compliance, coupled with a lack of education regarding PBs, their use and/or their importance. The ‘Family-oriented’ type was characterised by familial ties and a higher level of education that were strong drivers of compliance. The ‘Active’ patient type, consisted of the smallest proportion of respondents, was emotionally driven by their desire to control their disease and lead as normal a life as possible. Patient type clearly influenced compliance, with ‘Afflicted’ patients typically being least compliant and ‘Active’ patients being most compliant. Key influencers were also identified for each patient type: for example, ‘Afflicted’ patients tended to be relatively socially isolated and immobile, and thus making the dietician, nurse or dialysis clinic employee their most important contact with whom to discuss compliance; nephrologists were secondary level influencers of this patient type. Although internet use was prevalent among all patient types, it had far greater influence on ‘Family-oriented’ and ‘Active’ patient types. Conclusions: This study identified three types of CKD patient and prioritized drivers of compliance for each type. By recognizing key influencers for each patient type, this study provides a starting point for improving PB compliance in CKD patients. Patient education via HCPs and internet-based tools were identified as potentially successful methods for improving compliance. SP270ASSOCIATION OF ENDOCAN WITH INFLAMMATION, CARDIOVASCULAR EVENTS AND SURVIVAL IN CHRONIC KIDNEY DISEASE Mahmut I Yilmaz Mahmut I Yilmaz 1 Gulhane School of Medicine, Ankara, Turkey Dimitrie Siriopol Dimitrie Siriopol 2 C.I. Parhon University, Iasi, Romania Mutlu Saglam Mutlu Saglam 1 Gulhane School of Medicine, Ankara, Turkey Yasemin G Kurt Yasemin G Kurt 1 Gulhane School of Medicine, Ankara, Turkey Hilmi Unal Hilmi Unal 1 Gulhane School of Medicine, Ankara, Turkey Tayfun Eyileten Tayfun Eyileten 1 Gulhane School of Medicine, Ankara, Turkey Mahmut Gok Mahmut Gok 1 Gulhane School of Medicine, Ankara, Turkey Hakki Cetinkaya Hakki Cetinkaya 1 Gulhane School of Medicine, Ankara, Turkey Yusuf Oguz Yusuf Oguz 1 Gulhane School of Medicine, Ankara, Turkey Sebahattin Sari Sebahattin Sari 1 Gulhane School of Medicine, Ankara, Turkey Abdulgaffar Vural Abdulgaffar Vural 1 Gulhane School of Medicine, Ankara, Turkey Irina Mititiuc Irina Mititiuc 3 C.I. Parhon University, Iasi, Turkey Adrian Covic Adrian Covic 2 C.I. Parhon University, Iasi, Romania Mehmet Kanbay Mehmet Kanbay 4 Istanbul Medeniyet University School of Medicine, Istanbul, Turkey Abstract Introduction and Aims: Plasma Endocan levels are elevated in a large number of diseases, and may represent a novel endothelial cell dysfunction marker. However, there are no data on Endocan in chronic kidney disease (CKD) patients. Methods: Plasma Endocan was obtained from 251 CKD (stage 1 to 5) and 60 control patients and its concentration was correlated with glomerular filtration rate (GFR), and different markers of inflammation (pentraxin 3 (PTX3) and high-sensitive C reactive protein (hsCRP)) and vascular abnormalities (flow-mediated vasodilation (FMD) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed in relation with plasma Endocan levels. Results: Patients with CKD showed increased Endocan (4.7 [IR 1.9-9.4] vs 1.2 ng/mL [IR 1.1-1.5 ng/mL], p<0.001) levels, with values progressively higher across the CKD stages. In univariate analysis, plasma Endocan concentrations were correlated negatively with GFR and FMD, and positively with both markers of inflammation (PTX3 and hsCRP) and CIMT. However in multivariate analysis only GFR and PTX3 remained significantly associated with Endocan levels. In survival analysis, different Endocan levels independently predicted all-cause mortality and CVE in this patients. Conclusions: This is the first study that shows that Endocan levels increase in the presence of deteriorating eGFR and that its value influences, independently of traditional and non-traditional risk factors, all-cause mortality and CVE in the CKD population. SP271LONG-TERM EFFICACY AND SAFETY OF ORAL FEBUXOSTAT IN SUBJECTS WITH MODERATE-TO-SEVERE CHRONIC KIDNEY DISEASE: TWO-YEAR RESULTS Vassilis Filiopoulos Vassilis Filiopoulos 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Nikolaos Manolios Nikolaos Manolios 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Dimitrios Hadjiyannakos Dimitrios Hadjiyannakos 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Dimitrios Arvanitis Dimitrios Arvanitis 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Ioannis Karatzas Ioannis Karatzas 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Dimosthenis Vlassopoulos Dimosthenis Vlassopoulos 1 “Sismanogleion-Amalia Fleming” General Hospital, Athens, Greece Abstract Introduction and Aims: Hyperuricemia is currently considered an independent cardiovascular risk factor and an important mediator in renal disease development and progression. Febuxostat, a novel non-purine selective xanthine oxidase inhibitor, is more effective than allopurinol and equally safe in the management of chronic hyperuricemia. However, insufficient safety and efficacy data are available for Febuxostat administration to subjects with hyperuricemia and impaired renal function, in particular over the long term. This study was designed to prospectively evaluate long-term efficacy and safety of oral Febuxostat in hyperuricemic subjects with stages 3-4 chronic kidney disease (CKD). Methods: Fifteen patients, male/female 10/5, median age 70 (41-86) years with serum uric acid (sUA) ≥8.0 mg/dl and serum creatinine (sCr) ≥2.0 mg/dl received Febuxostat for two years. Nine out of 15 patients were previously on allopurinol and, due to intolerance, hypersensitivity or lack of efficacy, were switched to Febuxostat after a 15-day washout period. Patients with renal transplantation, active liver disease, alcohol abuse, concomitant treatment with azathioprine, mercaptopurine, theophylline or severe, life threatening medical condition were excluded. Febuxostat starting dose was 80 mg orally every other day with creatinine clearance estimated by Cockcroft-Gault formula (eCrCl C-G) ≥ 30 ml/min and every third day with < 30 ml/min. This dose was adjusted to achieve target sUA levels of ≤ 6 mg/dl. Hematology, biochemistry blood tests and creatinine clearance with 24-hr urine collection (24hr-CrCl) were performed and eCrCl C-G as well as eGFR MDRD4 were calculated at baseline and every other month thereafter. Adverse events were recorded. Results: sUA was significantly reduced already by month 2 of the study (9.9±1.6 vs. 5.7±1.3 mg/dl, p<0.001). This significant difference remained throughout the study period with stable and within target sUA levels up to month 24 (5.3±0.7mg/dl, p<0.001). Target sUA at the end of the study was achieved in 12/15 (80%) patients. Renal function, assessed by 24hr-CrCl, eGFR C-G and eGFR MDRD4 remained unchanged through month 24 (26.88±10.27 vs. 24.90±10.29 ml/min, 28.53±9.64 vs. 25.94±8.25 ml/min and 25.80±7.54 vs. 24.20±9.32 ml/min/1.73m2, respectively). No significant differences were observed for the rest of the studied parameters, including C-reactive protein (CRP), proteinuria and liver tests. Febuxostat weekly dose variation was similar throughout the study in all patients. No significant differences between males and females, diabetics and non-diabetics as well as CKD3 and CKD4 patients were observed in the Febuxostat sUA lowering effect or in renal function evolution during treatment. Gastrointestinal adverse events recorded in 2/15 (13.3%) patients were mild. Conclusions: Febuxostat, administered over two-year period in significantly reduced dosage, appears to be effective and safe with minimal side effects in the management of chronic hyperuricemia for patients with moderate-to-severe CKD. SP272N-TERMINAL PROHORMONE B-TYPE NATRIURETIC PEPTIDE IN CHILDREN WITH CHRONIC KIDNEY DISEASE Magdalena Okarska-Napierala Magdalena Okarska-Napierala 1 Medical University of Warsaw, Warsaw, Poland Helena Ziolkowska Helena Ziolkowska 1 Medical University of Warsaw, Warsaw, Poland Radoslaw Pietrzak Radoslaw Pietrzak 1 Medical University of Warsaw, Warsaw, Poland Piotr Skrzypczyk Piotr Skrzypczyk 1 Medical University of Warsaw, Warsaw, Poland Katarzyna Jankowska Katarzyna Jankowska 1 Medical University of Warsaw, Warsaw, Poland Bozena Werner Bozena Werner 1 Medical University of Warsaw, Warsaw, Poland Maria Roszkowska-Blaim Maria Roszkowska-Blaim 1 Medical University of Warsaw, Warsaw, Poland Abstract Introduction and Aims: Cardiovascular disease (CVD) is a frequent complication of chronic kidney disease (CKD) and a leading cause of increased mortality in young adults with CKD. One of biochemical markers of myocardial damage and stress is NT-proBNP. Its correlation with cardiac strain was proved in both adults and children with CKD.The aim of this study was to determine relations between serum levels of NT-proBNP, calcium-phosphorus metabolism parameters and echocardiographic results in children with CKD. Methods: 22 children, 10 boys, aged 10.9 ± 5.6 years, with CKD stage 2 - 5 were included in the study. In all children serum concentrations of creatinine, alkaline phosphatase (ALP), 25(OH)D, calcium (Ca), phosphorus (P), parathormone (PTH) and NT-proBNP were measured at one time. In 18 children echocardiography was performed as well. Results: Laboratory results are presented in the table. In group CKD 5 NT-proBNP and PTH levels were significantly increased. Concurrently, the highest levels of LVMI were observed in this group. NT-proBNP was found to correlate negatively with GFR (R = -0.61, p = 0.002) and positively with PTH (R = 0.49, p = 0.02) and P (R = 0.5, p = 0.02). Conclusions: In children with advanced CKD, calcium-phosphate metabolism disturbances may influence development of cardiovascular disease. Relationships between cardiac strain markers and other parameters of calcium-phosphate metabolism in children with CKD necessitate further investigation. Biochemical data . CKD 2 (n=6) . CKD 3-4 (n=10) . CKD 5 (n = 6) . p value . Overall (n=22) . NT-proBNP median (lower, upper quartile) 68 (32, 118) 106 (52, 158) 665.5 (317, 1579) 0.01*a 94 (52, 317) PTH median (lower, upper quartile) 49.25 (15.2, 56.9) 38 (29.6, 62.2) 199.5 (89, 656) 0.01*a 54.45 (35.9, 67.3) 25(OH)D median (lower, upper quartile) 22.05 (21.2, 29.6) 25.4 (16.4, 31.6) 32.85 (22.9, 37.8) NS 25.4 (21.2, 31.6) ALP median (lower, upper quartile) 194.5 (172, 204) 160 (96, 230) 269.5 (145, 407) NS 202 (134, 230) P mean±SD 2.8 ± 0.53 2.84 ± 0.43 3.32 ± 0.39 NS 2.96 ± 0.48 . CKD 2 (n=6) . CKD 3-4 (n=10) . CKD 5 (n = 6) . p value . Overall (n=22) . NT-proBNP median (lower, upper quartile) 68 (32, 118) 106 (52, 158) 665.5 (317, 1579) 0.01*a 94 (52, 317) PTH median (lower, upper quartile) 49.25 (15.2, 56.9) 38 (29.6, 62.2) 199.5 (89, 656) 0.01*a 54.45 (35.9, 67.3) 25(OH)D median (lower, upper quartile) 22.05 (21.2, 29.6) 25.4 (16.4, 31.6) 32.85 (22.9, 37.8) NS 25.4 (21.2, 31.6) ALP median (lower, upper quartile) 194.5 (172, 204) 160 (96, 230) 269.5 (145, 407) NS 202 (134, 230) P mean±SD 2.8 ± 0.53 2.84 ± 0.43 3.32 ± 0.39 NS 2.96 ± 0.48 * significant at p < 0.05 (Spearman test) a Between CKD 5 and either CKD 2 or CKD 3-4 normal value for NT-proBNP < 125.0 pg/ml Biochemical data . CKD 2 (n=6) . CKD 3-4 (n=10) . CKD 5 (n = 6) . p value . Overall (n=22) . NT-proBNP median (lower, upper quartile) 68 (32, 118) 106 (52, 158) 665.5 (317, 1579) 0.01*a 94 (52, 317) PTH median (lower, upper quartile) 49.25 (15.2, 56.9) 38 (29.6, 62.2) 199.5 (89, 656) 0.01*a 54.45 (35.9, 67.3) 25(OH)D median (lower, upper quartile) 22.05 (21.2, 29.6) 25.4 (16.4, 31.6) 32.85 (22.9, 37.8) NS 25.4 (21.2, 31.6) ALP median (lower, upper quartile) 194.5 (172, 204) 160 (96, 230) 269.5 (145, 407) NS 202 (134, 230) P mean±SD 2.8 ± 0.53 2.84 ± 0.43 3.32 ± 0.39 NS 2.96 ± 0.48 . CKD 2 (n=6) . CKD 3-4 (n=10) . CKD 5 (n = 6) . p value . Overall (n=22) . NT-proBNP median (lower, upper quartile) 68 (32, 118) 106 (52, 158) 665.5 (317, 1579) 0.01*a 94 (52, 317) PTH median (lower, upper quartile) 49.25 (15.2, 56.9) 38 (29.6, 62.2) 199.5 (89, 656) 0.01*a 54.45 (35.9, 67.3) 25(OH)D median (lower, upper quartile) 22.05 (21.2, 29.6) 25.4 (16.4, 31.6) 32.85 (22.9, 37.8) NS 25.4 (21.2, 31.6) ALP median (lower, upper quartile) 194.5 (172, 204) 160 (96, 230) 269.5 (145, 407) NS 202 (134, 230) P mean±SD 2.8 ± 0.53 2.84 ± 0.43 3.32 ± 0.39 NS 2.96 ± 0.48 * significant at p < 0.05 (Spearman test) a Between CKD 5 and either CKD 2 or CKD 3-4 normal value for NT-proBNP < 125.0 pg/ml SP273NEW THERAPEUTIC STRATEGIES UNDER DEVELOPMENT TO HALT THE PROGRESSION OF RENAL FAILURE Valeria Cernaro Valeria Cernaro 1 University of Messina, Messina, Italy Gianluca Trifirò Gianluca Trifirò 1 University of Messina, Messina, Italy Giuseppina Lorenzano Giuseppina Lorenzano 1 University of Messina, Messina, Italy Silvia Lucisano Silvia Lucisano 1 University of Messina, Messina, Italy Michele Buemi Michele Buemi 1 University of Messina, Messina, Italy Domenico Santoro Domenico Santoro 1 University of Messina, Messina, Italy Abstract Introduction and Aims: Chronic kidney disease (CKD) is a global concern since its incidence is constantly increasing. Accordingly, prevention of CKD onset and progression is mandatory. Since pharmacological agents already used in clinical practice are not yet able to halt the progression of renal damage, new therapeutic strategies are currently explored. We carried out a systematic review on phase 1/2 clinical trials, already concluded or ongoing, which aim at evaluating the safety and efficacy of novel therapeutic approaches to CKD. Methods: We performed the research through November 2013. Data were retrieved from scientific literature and from the ClinicalTrials.gov registry. We used the “advanced search” section of the ClinicalTrials.gov website and filled in the “search terms” field with the expression “chronic kidney disease”; then we selected “adult” and “senior” among the age groups, “phase 1” and “phase 2” as type of studies of interest, and all fields regarding funder type, namely “NIH”, “Other U.S. Federal Agency”, “Industry”, and “All others (Individual, University, Organization, …)”. By doing so, we obtained 238 records and among them, two expert nephrologists manually selected 44 clinical trials which specifically explored the drugs used to arrest the progression of renal disease. Then, we searched for the existence of publications related to the inserted clinical trials on Pubmed to get more information. Results: Several drugs are currently under investigation due to their supposed anti-proteinuric action, such as selective endothelin-A receptor antagonists or vitamin D analogues. Other drugs are being studied in CKD because of their anti-fibrotic, anti‐inflammatory and anti‐oxidative properties (e.g. LY2382770, pirfenidone and CTP-499) or due to the hypothetical ability to repair damaged podocytes (e.g. isotretinoin and BQ-123). A fascinating therapeutic approach involves the use of progenitor/stem cells. In most cases, studies have not yet been completed; some trials have been concluded but results are not available so far. Conclusions: Numerous clinical trials are evaluating new strategies to halt the progression of CKD. Many of them aim primarily at identifying pharmacological agents able to reduce proteinuria, a significant factor of progression of renal damage. Other drugs under investigation are thought to exert anti-fibrotic, anti-inflammatory and anti-oxidative effects that could interfere with tubulo-interstitial fibrosis. A further field of research is the use of stem cells that should repair renal tissue after an injury. We are still far from application of stem cells in clinical practice but remarkable progresses have been achieved in the understanding of their biology and behaviour as well as in the procedures required to mobilize and activate endogenous stem-cells in damaged kidneys or to introduce exogenous stem cells for tissue repair. If these studies report positive results, nephrologists will be provided with the opportunity to slow down CKD progression, a constantly increasing serious health issue worldwide which is associated with high morbidity and mortality. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP274FITNESS AS PART OF COMPREHENSIVE CARE IN CKD: IMPROVEMENT IN BODY STRENGTH AND SELF-CONFIDENCE Rolfdieter Krause Rolfdieter Krause 1 ReNi-German Society Renal Rehabilitation, Berlin, Germany 2 KfH-Kuratorium for Dialysis and Kidney Transplantation, Berlin, Germany 3 EURORECKD-European Association Renal Rehabilitation, Berlin, Germany Iris Fuhrmann Iris Fuhrmann 1 ReNi-German Society Renal Rehabilitation, Berlin, Germany 3 EURORECKD-European Association Renal Rehabilitation, Berlin, Germany Stefan Degenhardt Stefan Degenhardt 1 ReNi-German Society Renal Rehabilitation, Berlin, Germany 3 EURORECKD-European Association Renal Rehabilitation, Berlin, Germany 4 Nephrological Center, Nettetal, Germany Anton E. Daul Anton E. Daul 1 ReNi-German Society Renal Rehabilitation, Berlin, Germany 3 EURORECKD-European Association Renal Rehabilitation, Berlin, Germany 5 Elisabeth-Hospital, Essen, Germany Abstract Introduction and Aims: ESKD patients suffer from poor physical capacity mainly from muscle wasting due to uremic myopathy and polyneuropathy and following physical inactivity. - The aim of this multicenter study was to examine the effects of a structured strength-endurance training therapy during dialysis on physical functional capacity and self perceived health related quality of life (HRQoL). Methods: 46 ESKD patients (age range 28-59 yrs., 59% over 60 yrs.) exercised twice weekly for 30 - 60 mins. over a period of 26 weeks. Training was structured using 52% strength exercises and 48% endurance (bed-ergometry). - Before starting and at the end the following tests were performed: Timed-Stand-Up-and-Go-Test [SUG], 1-min-Sit-to-Stand-to-Sit-Test [SSS], maximal Bicycle-Ergometry [ERGO], and SF-36-Questionnaire: Physical Component Score [PCS] and Mental Component Score [MCS]. Results: There were significant [p < 0.05] increases in all three functional tests: SUG +18%, SSS +13.5%, ERGO +16.7%. - There were significant correlations between the functional tests and self perceived HrQoL: PCS vs. SUG: r2 = 0.062, PCS vs. SSS: r2 = 0.102, PCS vs. ERGO: r2 = 0.014. - Moreover, training participation per se correlated to PCS: r2 = 0.677, and MCS: r2 = 0.411, respectively. Conclusions: Structured training therapy is able to improve body strength and strength-endurance. The increase in physical function also improved self-confidence of the patients as measured by the SF-36. - Thus, structured exercise training therapy is an effective non-medical treatment also in ESKD patients on hemodialysis. Comprehensive care in CKD should include the same modes for improving physical fitness as recommended for the most frequent causes of renal failure, diabetes and hypertension, as well as for the general population. SP275INDOLE-3 ACETIC ACID PREDICTS CARDIOVASCULAR EVENT AND MORTALITY IN CHRONIC KIDNEY DISEASE PATIENTS: EVIDENCE FOR AN ENDOTHELIAL INFLAMMATORY AND PROOXIDANT EFFECT Marion Sallee Marion Sallee 1 APHM, Marseille, France 2 Aix-Marseille Université, Marseille, France Laetitia Dou Laetitia Dou 2 Aix-Marseille Université, Marseille, France Claire Cerini Claire Cerini 2 Aix-Marseille Université, Marseille, France Stéphane Poitevin Stéphane Poitevin 2 Aix-Marseille Université, Marseille, France Bertrand Gondouin Bertrand Gondouin 1 APHM, Marseille, France Noémie Jourde-Chiche Noémie Jourde-Chiche 1 APHM, Marseille, France Philippe Brunet Philippe Brunet 1 APHM, Marseille, France Françoise Dignat-George Françoise Dignat-George 2 Aix-Marseille Université, Marseille, France Stéphane Burtey Stéphane Burtey 1 APHM, Marseille, France 2 Aix-Marseille Université, Marseille, France Abstract Introduction and Aims: In chronic kidney disease (CKD), uremic solutes could induce endothelial dysfunction, inflammation, and oxidative stress, leading to increased cardiovascular risk. We investigated whether the uremic solute indole-3 acetic acid (IAA) predicts clinical outcomes in CKD patients and contributes to cardiovascular disease via prooxidant and proinflammatory mechanisms. Methods: We performed a clinical study including CKD patients at different stage. This population was divided in two groups according to IAA serum levels. Mortality and major cardiovascular events were prospectively collected during 1100 days. In vitro, endothelial dysfunction induced by IAA was studied. Results: 120 CKD patients were enrolled. During the study period, 29 patients died and 35 patients experienced a major cardiovascular event. Kaplan-Meier analysis revealed that mortality and cardiovascular events were significantly higher (respectively p = 0.013 and p = 0.024) in the higher IAA group (> 3.73 µM) compared to the lower IAA group (IAA < 3.73 µM). Multivariate Cox proportional hazard analysis demonstrated that serum IAA was a significant predictor for mortality and cardiovascular event, after various adjustments including age, mal gender (model 1), albumin, phosphate, CRP (model 2), LDL-cholesterol, systolic blood pressure and smoking (model 3). IAA levels were positively correlated with markers of inflammation and oxidative stress, respectively C-reactive protein and malondialdehyde. In cultured human endothelial cells, IAA had a pro-oxidative and a pro-inflammatory effect. In endothelial cells, IAA activated an inflammatory pathway that led to the induction of the proinflammatory enzyme Cyclooxygenase-2. In addition, IAA increased endothelial reactive oxygen species production. Conclusions: In conclusion, serum IAA is a significant predictor for mortality and cardiovascular event in CKD patients. IAA could be involved in cardiovascular disease associated with CKD by inducing endothelial inflammation and oxidative stress. SP276ASSOCIATION BETWEEN LOW SERUM MAGNESIUM LEVELS AND THE EXTENT OF ATHEROSCLEROTIC PROCESS IN HAEMODIALYSIS PATIENTS Carlo Massimetti Carlo Massimetti 1 Centro Di Riferimento Di Nefrologia e Dialisi, Viterbo, Italy Paola Achilli Paola Achilli 2 Cardiologia, Viterbo, Italy Maria Pina P Madonna Maria Pina P Madonna 2 Cardiologia, Viterbo, Italy Maria Teresa T Muratore Maria Teresa T Muratore 3 Laboratorio Analisi, Viterbo, Italy Gian Domenico D Fabbri Gian Domenico D Fabbri 4 Radiologia, Viterbo, Italy Franco Brescia Franco Brescia 4 Radiologia, Viterbo, Italy Sandro Feriozzi Sandro Feriozzi 1 Centro Di Riferimento Di Nefrologia e Dialisi, Viterbo, Italy Abstract Introduction and Aims: Vascular damage in haemodialysis patients is the result of a mix between traditional and a growing number of non-traditional risk factors. Recent experimental and clinical studies showed that magnesium deficiency may be related to the progression of atherosclerosis and of vascular calcification. Nevertheless magnesium’s role in these process has been underestimated till now, despite it plays a physiological role in many functions, including anti-inflammatory and antiplatelet activities.The aim of this study was to determine the hypothetical association between sMg and carotid artery alterations in a haemodialysis population. Methods: Ultrasonographic assessments of carotid artery intima-media thickness (CIMT) was evaluated in a group of 180 haemodialysis patients recruited between 2006 and 2012. In all patients were determined sCa, sPO4, sMg, PTH, HDL- and LDL cholesterol, hematocrit, homocysteine, C-reactive protein (CRP), systolic and diastolic blood pressure (SBP, DBP), intake of calcium salts and calcitriol. In 131 patients was also performed echocardiographic examination.In all patients were recoded previous cardiovascular events (CVE). Results: Mean age was 56 ± 15 y/o, 89/91 (M/F), diabetes 13%, CVE were recorded in 17% of the patients, CIMT was on average 1.41 ± 0.75 mm. Serum Mg was negatively correlated with age, CVE, CRP, and CIMT (r=-.164, P<.05; r=-.194, P<.01; r=-.214, P<.01; r=-.232, P<.01; respectively). Stepwise multiple regression analysis showed that the final model contained five predictor variables for CIMT (age, sPO4,sMg, PTH, SBP and DBP; F7,173=19.99, P<.001; Adjusted R square =.426). Patients in the first sMg quartile (< 1.8 mg/dl) were significantly older, with higher CIMT values, and with larger number of CVE. CIMT was correlated with age, dialysis vintage, sPO4, PTH, CRP, homocysteine, and DBP (r= .542, P<.001; r= .216, P<.01; r=.203, P<.01; r=.151, P<.05; r=.199, P<.05; r=.194, P<.05; r=-.212, P< .01; respectively). Left ventricular mass index (LVMi) was significantly correlated with CIMT, SBP, DBP, and sPO4 (r=.227, P<.01; r=-.324, P<.001; r=.234, P<.01; r=-.229, P<.01; respectively). Conclusions: In conclusion our experience confirm the role of some traditional and no-traditional factors as old age, SBP, DBP, and sPO4 levels in the extent of atherosclerotic process in haemodialysis patients, but at the same time corroborate the hypothesis concerning a role of low sMg levels in this process. Moreover our results suggest a hypothetical interrelationship between sMg, CIMT and LVMi. Further investigations are needed to examine the relationship between sMg levels and the incidence of cardiovascular disease. SP277THE IMPORTANCE OF SERUM CXCL-16 LEVELS IN PATIENTS WITH GRADE III-V CHRONIC RENAL FAILURE Hilmi Umut Ünal Hilmi Umut Ünal 1 Gulhane School of Medicine Department of Nephrology, Ankara, Turkey Yasemin Gülcan Kurt Yasemin Gülcan Kurt 2 Department of Biochemistry, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Mahmut Gök Mahmut Gök 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Hakkı Çetinkaya Hakkı Çetinkaya 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Murat Karaman Murat Karaman 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Tayfun Eyileten Tayfun Eyileten 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Abdulgaffar Vural Abdulgaffar Vural 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Yusuf Oguz Yusuf Oguz 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Mahmut I˙lker Yılmaz Mahmut I˙lker Yılmaz 3 Department of Nephrology, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey Abstract Introduction and Aims: CXCL16 functions as a scavenger receptor, which is synthesised in plasmacytoid dendritic cell as a transmembrane molecule ,playing a prominent role in the pathogenesis of atherosclerosis.In addition to its role in atherosclerotic vascular diseases, animal studies indicate, blocking CXCL16 attenuated monocyte/macrophage infiltration and glomerular injury, deletion of CXCL16 attenuated renal fibrosis. These findings implicate CXCL16 to play an considerable role in the onset and progression of kidney disease. Methods: 222 patients with chronic renal disease were included in the study. The patients were devided into 3 groups according to glomerular filtration rate (GFR) in accordance with K/DOQI guideline. 73 patients were grade 3, 73 patients were grade 4 and 76 patients were grade 5 chronic renal failure. Patients with active glomerulonephritis or tubulointerstitial nephritis, heart failure, and hepatic disease, patients who use immunosuppressive or cytotoxic drugs and blockers of renin-angiotensin system and smokers were exluded from the study. Results: There was a positive correlation between the grade of renal failure and CXCL-16 and negative correlation between eGFR and CXCL-16 (r=-0.457, p<0.001). There was a negative correlation between hsCRP and eGFR. Endothelial function was impaired as parallel to CKD progression and hsCRP values increased as a sign of this positive correlation (r = -0,499, p <0.001). There was a positive correlation between CXCL-16 and hsCRP (r = 0.359 p <0.001). Decreased eGFR, increased PTH and hsCRP levels and presence of DM and HT were associated with serum CXCL-16 elevation in multipl regression analysis (Figure1) Conclusions: The previous study by Lin et al. indicated that plasma CXCL16 levels were positively associated with adiponectin, serum phosphate, ESR and uric acid (all p < 0.05) and correlated negatively with HDL-c (p < 0.05) and eGFR (p < 0.001) (5).These studies suggest that inhibition of CXCL16 could constitute a novel therapeutic approach for chronic kidney disease. Our results indicated that decresed GFR levels were associated with increased hsCRP and CXCL-16 in chronic renal disese. It is concluded that this chemokine which has relation with Framingham risk factors, plays important role in progression of renal disease and development of complications. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP278INFLUENCE OF KIDNEY DYSFUNCTION ON FUNCTIONAL OUTCOME AFTER CEREBRAL INFARCTION Mai Sugahara Mai Sugahara 1 Mitsui Memorial Hospital, Tokyo, Japan Izumi Sugimoto Izumi Sugimoto 1 Mitsui Memorial Hospital, Tokyo, Japan Mari Aoe Mari Aoe 1 Mitsui Memorial Hospital, Tokyo, Japan Masatomo Chikamori Masatomo Chikamori 1 Mitsui Memorial Hospital, Tokyo, Japan Tomoko Honda Tomoko Honda 1 Mitsui Memorial Hospital, Tokyo, Japan Rika Miura Rika Miura 1 Mitsui Memorial Hospital, Tokyo, Japan Ayako Tsuchiya Ayako Tsuchiya 1 Mitsui Memorial Hospital, Tokyo, Japan Kensuke Hamada Kensuke Hamada 1 Mitsui Memorial Hospital, Tokyo, Japan Kenichi Ishizawa Kenichi Ishizawa 1 Mitsui Memorial Hospital, Tokyo, Japan Katsunori Saito Katsunori Saito 1 Mitsui Memorial Hospital, Tokyo, Japan Yasuhisa Sakurai Yasuhisa Sakurai 1 Mitsui Memorial Hospital, Tokyo, Japan Naobumi Mise Naobumi Mise 1 Mitsui Memorial Hospital, Tokyo, Japan Abstract Introduction and Aims: We previously showed that patients with decreased kidney function tended to have thrombosis of larger vessels in cerebral infarction. The aim of the current study was to examine the relationship between kidney function and functional status after stroke. Methods: In this retrospective observational study, we examined 119 patients with atherothrombotic cerebral infarction (95 men, 68 ± 12 years old) and 52 lacunar infarction (36 men, 64 ± 10 years old) who were admitted to our hospital between April 2009 and October 2012. We included only patients with pre-stroke score on the modified Rankin Scale (mRS) of 0, namely no disability. The patients were divided into 2 groups on the basis of their kidney function: Group A, estimated glomerular filtration rate (eGFR)≥ 60ml/min/1.73 m2 (n = 121); Group B, eGFR < 60 mL/min/1.73 m2 (n = 50, including 9 dialysis patients). The functional status at discharge was assessed using the mRS. Results: Among atherothrombotic cerebral infarction, 80 patients belonged to Group A (67%) and 39 to Group B (33%). Thirteen patients in Group A (16%) and 8 in Group B (21%) had a mRS of 3-6 (moderate-to-severe disability or death) at discharge (p = 0.57). On the other hand, the cohort of lacunar infarction had 41 patients in Group A (79%) and 11 in Group B (21%). In both groups, 2 patients were discharged with a mRS greater than 3 (5% in Group A versus 18% in Group B, p = 0.14). The prevalence of hypertension, diabetes, and dyslipidemia, was comparable between Group A and B. Conclusions: Although the percentage of patients with moderate-to-severe disability or death after cerebral infarction was higher in the cohort with kidney dysfunction, the difference was not statistically significant. SP279POSTPRANDIAL RESPONSES OF CIRCULATING PANCREATIC POLYPEPTIDE (PP) AND INCRETIN LEVELS IN HEMODIALYSIS PATIENTS FOLLOWING A STANDARDIZED MEAL Thiane Gama-Axelsson Thiane Gama-Axelsson 1 Karolinska Institutet, Stockholm, Sweden Borja Quiroga Borja Quiroga 2 Hospital General Universitario Gregorio Marañón, Madrid, Spain Jonas Axelsson Jonas Axelsson 1 Karolinska Institutet, Stockholm, Sweden Bengt Lindholm Bengt Lindholm 1 Karolinska Institutet, Stockholm, Sweden Abdul Rashid Qureshi Abdul Rashid Qureshi 1 Karolinska Institutet, Stockholm, Sweden Juan Jesus Carrero Juan Jesus Carrero 1 Karolinska Institutet, Stockholm, Sweden Abstract Introduction and Aims: Satiety and poor appetite are common in hemodialysis (HD) patients by mechanisms not yet fully elucidated. Plasma pancreatic polypeptide (PP) may be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In this intervention study, we analyzed the impact of a fat and carbohydrate -rich meal on pancreatic polypeptide (PP) and duodenal incretin responses in HD patients. Methods: Six HD patients (17% females; age of 52(40-62) years; body mass index (BMI) 22(19-24) kg/m2) and 9 healthy subjects (HS) (55% females; age of 48(43-52) years; BMI 26(24-30) kg/m2) received a standardized test meal consisting of 75 g of milk fat, 80 g of carbohydrates and 6 g of proteins/m2 of body surface area. Fasting and postprandial circulating levels of PP, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) as well as glucose and triglycerides were measured. Postprandial responses over 240 min were evaluated using area under the curve (AUC) values for the studied peptide hormones. Results: The median baseline serum level of PP was six fold higher in HD patients than in HS 1154 (554-1969) vs 180 (61-691) µg/mL; p=0.01) and the postprandial PP response was also significantly higher in HD patients when compared with HS (AUC [median (25-75 percentile)] 618225 [200591-752910] vs 74010 [36315- 172560 µg/mL/min]; p<0.05). Fasting GIP was higher in HD patients than in HS (22.1 (13.3-23.3) vs 7.1 (5.3-10.6) pmol/L; p=0.01) while postprandial responses of GIP, GLP-1, triglycerides and glucose levels were similar between the two groups. Conclusions: The fasting PP and GIP levels, and the postprandial PP response, were higher in HD patients compared to HS whereas postprandial responses of glucose, triglycerides, GIP and GLP-1 were similar in patients and HS. We speculate that an elevated PP response may be involved in the commonly observed prolonged feeling of fullness and poor appetite of this patient population. SP280REGULAR AQUATIC EXERCISE FOR CHRONIC KIDNEY DISEASE PATIENTS: A TEN-YEAR FOLLOW-UP STUDY Ülle Pechter Ülle Pechter 1 Tartu University, Tartu, Estonia Mait Raag Mait Raag 1 Tartu University, Tartu, Estonia Mai Ots-Rosenberg Mai Ots-Rosenberg 1 Tartu University, Tartu, Estonia Abstract Introduction and Aims: Chronic kidney disease (CKD) patients not yet in dialysis can benefit from increased physical activity but the safety and outcomes of aquatic exercise are not been investigated in observational studies. The aim of the study was to analyze associations of ten-year regularly performed aquatic exercise with study end-point - all-cause death or start of dialysis. Methods: Consecutive CKD patients were involved in the study in January 2002. The exercise group (n=7) exercised regularly during ten years, the control group (n=9), matched in age and clinical parameters, remained sedentary. The low-intensity aerobic aquatic exercise was performed twice a week; 32 weeks or more sessions were performed annually. Results: From the exercise group nobody reached dialysis or died. From the sedentary group 55% (n=5) reached the study end-point - dialysis or all-cause death. Change in renal parameters between 2002 and 2012 did not differ significantly (Wilcoxon rank sum test p-value: 0.921) between the two groups. However, occurrence of study endpoint, compared with exact multinomial test with unconditional margins, indicated that occurrence of study endpoint was statistically significantly different (p-value: 0.037) between the study groups. Conclusions: Aquatic exercise arrested CKD progression. There was statistically significant difference between the sedentary group and exercise group in reaching renal replacement therapy or all-cause death in ten years of follow-up time. SP281SAFETY AND EFFICACY OF ECULIZUMAB IN PEDIATRIC PATIENTS WITH aHUS, WITH OR WITHOUT BASELINE DIALYSIS Johan Vande Walle Johan Vande Walle 1 UZ Gent Dienst Nefrologie, Ghent, Belgium, Ghent, Belgium Larry A Greenbaum Larry A Greenbaum 2 Emory University, Atlanta, GA Camille L. Bedrosian Camille L. Bedrosian 3 Alexion Pharmaceuticals, Inc., Cheshire, CT Masayo Ogawa Masayo Ogawa 3 Alexion Pharmaceuticals, Inc., Cheshire, CT John F. Kincaid John F. Kincaid 3 Alexion Pharmaceuticals, Inc., Cheshire, CT Chantal Loirat Chantal Loirat 4 Assistance Publique-Hôpitaux de Paris, Paris, France Abstract Introduction and Aims: Atypical hemolytic uremic syndrome (aHUS) is characterized by chronic, uncontrolled complement activation and TMA. aHUS is associated with a high mortality and morbidity rate - 29% of children with aHUS progress to ESRD or die within the first year of diagnosis. Eculizumab (ecu) inhibits complement-mediated TMA and has been shown to improve eGFR in pediatric patients (pts) with aHUS, including those with a history of dialysis. The objective of this analysis was to characterize the safety and efficacy of ecu in pts with dialysis (DIAL) and without dialysis (N-DIAL) at baseline (BL) in the first-ever prospective trial of ecu in pediatric pts with aHUS. Methods: A sub-analysis of an open-label, single-arm trial to evaluate safety and efficacy of ecu in pts with aHUS aged 1 month to <18 years and body weight ≥5kg was performed. Primary study outcome was the proportion of pts who achieved complete TMA response during 26 wks of ecu tx. Pts were vaccinated against N. meningitidis. Inclusion criteria included platelet (plt) count <150 x 109/L, LDH ≥1.5 x ULN, and sCR ≥97th percentile for age at screening. Exclusion criteria included pts with severe ADAMTS-13 deficiency (ADAMTS-13 activity <5%) and pts with Shiga-toxin-producing E. coli infection. Results: The table below lists BL characteristics and efficacy outcomes at Wk 26 -- 11 pts in each sub-group. 12 of 22 (55%) pts received ecu without first receiving plasma exchange/infusion. Ecu improved plt count (x109/L) in both DIAL (149.8, P=0.0150) and N-DIAL (180.2, P=0.0003) pts. eGFR (mL/min/1.73 m²) improved in DIAL (57.7, P=0.0568) and N-DIAL (70.3, P=0.0056) pts. Of BL DIAL pts, 9/11 (82%) discontinued dialysis by 26 wks. No pt needed to resume dialysis (DIAL) or started new dialysis (N-DIAL). At Wk 26, all pts in both sub-groups were dialysis-free. The treatment-emergent adverse event profile was similar for both groups. Conclusions: Ecu tx resulted in clinically meaningful improvements in hematologic and renal parameters in BL DIAL and N-DIAL pediatric pts with aHUS. 82% of BL DIAL pts discontinued dialysis by Wk 26, and no N-DIAL pt started new dialysis. Increases in eGFR from BL were observed for both DIAL and N-DIAL pts at Wk 26. The results of this sub-analysis are consistent with previously reported data from a retrospective ecu trial in 19 pediatric pts (aged 2 months to 17 years), whereby no pt required new dialysis during ecu tx. Together, these data provide additional support that ecu is a proven, effective, and safe tx in all pediatric pts with aHUS, regardless of prior dialysis. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP282QUANTITATIVE RENAL ECHOGENICITY IS COMPARABLE TO HISTOPATHOLOGY IN PREDICTING IRREVERSIBILITY OF IMPAIRED RENAL FUNCTION Alexandre Liborio Alexandre Liborio 1 University Federal of Ceara, Fortaleza, Brazil Tacyano Tavares Leite Tacyano Tavares Leite 1 University Federal of Ceara, Fortaleza, Brazil Fernanda Macedo de Oliveira Neves Fernanda Macedo de Oliveira Neves 1 University Federal of Ceara, Fortaleza, Brazil Candice Bezerra Torres De Melo Candice Bezerra Torres De Melo 1 University Federal of Ceara, Fortaleza, Brazil Renata de Almeida Leitão Renata de Almeida Leitão 2 University of Fortaleza - UNIFOR, Fortaleza, Brazil Lara Cunha Lara Cunha 1 University Federal of Ceara, Fortaleza, Brazil Reginaldo Filho Reginaldo Filho 1 University Federal of Ceara, Fortaleza, Brazil Abstract Introduction and Aims: Glomerulopathy patients are prone to developing reversible acute kidney injury (AKI), which can be difficult to differentiate from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful, but differently from renal length, quantitative renal echogenicity has not been formerly evaluated regarding its capacity to identify irreversible advanced CKD. Methods: A prospective study was performed, where quantitative renal echogenicity was performed during renal biopsy in patients with suspected suspected glomerular disease (n=197). Quantitative echogenicity was measured as the inverse of the ratio between the mean pixel densities of the renal cortex and adjacent liver using ScionImage software. Patients were followed during a six-months period to ascertain advanced CKD. Quantitative renal echogenicity and histopathology parameters discriminatory capacity were compared regarding their capacity to detect advanced and irreversible CKD - estimated glomerular filtration rate (eGFR) less than 30mL/min/1.73m2 confirmed after a six-month follow-up. Results: From 255 patients, 197 were included in the final analysis. At renal biopsy, the mean eGFR was 53.9±33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR less than 30 mL/min/1.73m2. After the follow-up period, 54 (27.4%) patients were considered as having advanced CKD (eGFR less than 30 mL/min/1.73m2). Mean kidney/liver echogenicity ratio was 1.06±0.29. Renal echogenicity correlated with all histopathological parameters. Renal echogenicity was directly correlated with 24h-proteinuria (r=0.216, p=0.008) and inversely with serum albumin (r=-0.201, p=0.011).Multivariate analysis was performed to calculated a combined histopathology index (HI). Renal echogenicity discriminatory capacity to identify true advanced CKD is shown in figure. Kidney/liver echogenicity ratio greater than 1.15 was the best disciminator. Using this cutoff, 65 (33.0%) patients had elevated renal echogenicity. We compared cortical echogenicity performance against HI index. They had very similar discriminatory capacity - table. When analyzing only patients with eGFR less than 30 mL/min/1.73m2 at the renal biopsy, the positive preditive of high echogenicity was 92.1% [75.6 -98.7]. In the studied population, 33 (16.7%) patients had more than 20% of glomeruli with crescent lesions. In this subpopulation, 11 (33.3%) patients had advanced CKD. Again, renal echogenicity had a good discriminatory capacity to detect advanced CKD - AuROC: 0.872 [0.736 - 1.000] and a PPV of 72.7% - while IF/II index had an AuROC of 0.806 [0.660 - 0.952] and PPV of 50%. Conclusions: Quantitative renal echogenicity can be a useful tool in patients with glomerular disease and normal kidney size (>8cm) to identify those patients with irreversible advanced CKD. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide Fig. 2 Open in new tabDownload slide SP283TIME TO IMPROVEMENTS IN ECULIZUMAB TREATED PATIENTS WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME AND PROGRESSING THROMBOTIC MICROANGIOPATHY: 3-YEAR UPDATE Neil Sheerin Neil Sheerin 1 Newcastle University, Newcastle-upon-Tyne, United Kingdom Chantal Loirat Chantal Loirat 2 Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France Larry Greenbaum Larry Greenbaum 3 Emory University, Atlanta, GA Richard Furman Richard Furman 4 Weill Cornell Medical College, New York, NY David Cohen David Cohen 5 Columbia University Medical Center, New York, NY Yahsou Delmas Yahsou Delmas 6 CHU de Bordeaux, Bordeaux, France Camille L. Bedrosian Camille L. Bedrosian 7 Alexion Pharmaceuticals, Inc., Cheshire, CT Christophe Legendre Christophe Legendre 8 Universite Paris Descartes and Hôpital Necker, Paris, France Abstract Introduction and Aims: Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disease, characterised by systemic thrombotic microangiopathy (TMA) resulting from complement activation. Eculizumab (Ecu), a terminal complement inhibitor, is the only approved aHUS treatment. We report a 3-yr update of time to improvement in a prospective clinical study evaluating Ecu efficacy and safety in patients (pts) with evidence of progressing TMA. Methods: A 26-wk, open-label, single-arm study was followed by a long-term extension. Pts were aged ≥12 yrs and had aHUS with progressing TMA (platelet count <150 x 109/L despite ≥4 plasma exchange/plasma infusion sessions 1 wk before screening). Pts received Ecu 900 mg/wk for 4 wks, 1200 mg at wk 5 and 1200 mg q2w thereafter. There were two primary endpoints: 1) TMA inhibition (platelet count change from baseline [BL]); 2) haematologic normalisation (platelet count ≥150 x 109/L and LDH ≤ upper limit of normal). Renal function was evaluated with secondary endpoints: serum creatinine decrease ≥25%; estimated glomerular filtration rate (eGFR) improvement ≥15 mL/min/1.73 m2; and CKD improvement ≥1 stage. Results: Of 17 enrolled pts (median [range] age 28 [17-68] yrs; 12 [71%] female; 12 [71%] with identified complement mutation/autoantibody), 13 continued into the extension. At the 3-yr update, median (range) treatment duration was 100 (2-186) wks; 5 pts were treated for >130 wks, 7 for 72-130 wks and 5 for <72 wks. Ongoing, long-term Ecu treatment sustained or improved key haematologic and renal endpoints (Fig 1). Mean (SD) BL platelet count was 109 (32) x 109/L, LDH 322 (138) U/L, and eGFR 22.9 (14.5) mL/min/1.73m2. Mean (95% CI) eGFR improvement at wk 156 was 54.0 (11.8-96.1) mL/min/1.73m2 (P=0.03). Of 5 pts on dialysis at BL, 4 (80%) discontinued dialysis by wk 26, with 3 remaining dialysis-free through 3 yrs. Analysis of 5 pts treated with Ecu for ≥30 mo showed maintained improvement compared to the 2-yr analysis; 4 of 5 pts (80%) improved CKD status by ≥1 stage. Adverse event rates remained the same or declined with ongoing Ecu. There were no deaths. Conclusions: This study shows haematologic parameters normalized more rapidly than renal parameters. The ameliorations in both haematologic and renal endpoints in Ecu-treated pts with aHUS and progressing TMA were generally sustained as of the 3-yr update. These results highlight the long-term efficacy of Ecu; slower improvement of the renal function supports the need for continued therapy even after initial hematologic improvement. Further long-term data are currently being collected in a global aHUS patient registry and a long-term follow-up observational study. Fig 1. Open in new tabDownload slide Cumulative percentages of pts achieving a) haematologic endpoints and b) renal endpoints Fig 1. Open in new tabDownload slide Cumulative percentages of pts achieving a) haematologic endpoints and b) renal endpoints SP284THE EFFECTS OF TOLVAPTON ON SEVERE CHRONIC KIDNEY DISEASE PATIENTS WITH CONGESTIVE HEART FAILURE Kiyoto Koibuchi Kiyoto Koibuchi 1 Saiseikai Yokohama-City Eastern Hospital, Yokohama, Japan Toshiyuki Aoki Toshiyuki Aoki 1 Saiseikai Yokohama-City Eastern Hospital, Yokohama, Japan Moriatsu Miyagi Moriatsu Miyagi 1 Saiseikai Yokohama-City Eastern Hospital, Yokohama, Japan Ken Sakai Ken Sakai 2 Toho University School of Medicine, Tokyo, Japan Atsushi Aikawa Atsushi Aikawa 2 Toho University School of Medicine, Tokyo, Japan Abstract Introduction and Aims: Tolvaptan is a selective vasopressin receptor 2 antagonist and dose-dependent drug used to treat congestive heart failure (CHF) as diuretic. It is known that tolvaptan increases excretion of excess fluids and improves blood sodium levels in patients with heart failure without affecting renal function compared to conventional diuretics. However, few studies examined the effects of tolvaptan for patients with severe chronic kidney disease (CKD). The aim of the study is to examine the effect of tolvaptan on severe CKD patients. Methods: We administrated tolvaptan (Doses 12.0±5.8 mg) for 75 non-dialysis CKD patients with less than 30 of estimated glomerular filtration rate (male/female: 42/33, 75.2±13.3 years old) in admission. Those of all patients have already treated conventional diuretics. The patients who changed the dose of conventional diuretics in observation period were excluded. To evaluate the effect of tolvapton, the following data were collected from the electric record for three days after administration: age, sex, presence of diabetes, blood pressure, urine volume, body weight, estimated glomerular filtration rate (eGFR), serum sodium concentration, hemoglobin, serum albumin, serum bicarbonate, brain natriuretic peptide (BNP), and cardiac ejection fraction. We defined 20% increase of urine output from baseline after administration of tolvaptan as responder and statistical analysis was used by logistic regression models. Results: Tolvaptan increased urinary volume from 1141.1±539.5 ml/day to 1864.5±1008.2 ml/day (p<0.001, Wilcoxon signed-rank test), improved Body weight from 59.7 ± 17.6 kg to 57.8 ± 17.0 kg (p<0.01, Wilcoxon signed-rank test), and elevated serum sodium from 132 ± 6.3 mEq/l to 139.4 ± 6.4 mEq/l (p=0.03, ANOVA and Dunnett’s testing). eGFR (17.8±7.4 at baseline) remained 17.1±8.7 after administration (p=0.34, Wilcoxon signed-rank test). In univariate analysis, eGFR (Odds ratio 1.43, 95%CI 1.11-1.65, p=0.003), urine volume at baseline (1.87, 1.45-2.14, p<0.001), and cardiac ejection fraction (1.18, 1.11-1.34, p=0.008) were associated with responder. In multivariate analysis, eGFR (Odds ratio 1.30, 95%CI 1.19-1.45, p=0.02), urine volume at baseline (1.67, 1.36-1.99, p=0.004) were remained significant after adjusted for age, sex, eGFR, serum albumin, urine volume, and cardiac ejection fraction. Conclusions: Tolvaptan is effective diuretic even with sever CKD patients, resistance to conventional diuretics, without worsening renal function, but the effectiveness decreases for the patients with lower eGFR and urine volume at baseline. SP285THE STATE OF KNOWLEDGE IN DIALYSIS AND RENAL OUTPATIENTS ON THE POTENTIAL NEPHROTOXICITY OF ANALGESICS Paweł PoznańSki Paweł PoznańSki 1 Wroclaw Medical University, Wroclaw, Poland MałGorzata Sojka MałGorzata Sojka 1 Wroclaw Medical University, Wroclaw, Poland Mariusz Kusztal Mariusz Kusztal 1 Wroclaw Medical University, Wroclaw, Poland Marian Klinger Marian Klinger 1 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction and Aims: According to the analysis of the Polish pharmaceutical market, analgesics are one of the most popular class of drugs. The wide, including over the counter (OTC) availability, high efficacy in commonly occurring ailments cause that the among OTC, painkillers account for 85% of drug sales. Popularizing effect may also have the fact that drugs are advertised as safe and free of side effects. Aim of the study was to examine the state of knowledge about the potential nephrotoxicity of medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen among renal outpatients. Methods: The survey was distributed among 250 encountered patients on dialysis (100) and in ambulatory settings (150). Responders were 55 hemodialyzed and 115 renal (CKD 2-4) outpatients (89 females and 81 males) with mean age 53,6 ±15 y (range 21-78y); response rate 68%. The questionnaire consisted of 29 inquiries of a medical history including pharmacotherapy, a frequency and quantity of pain medication, reading the enclosed leaflet, potential side effects of these drugs and communication with physicians and pharmacists. Results: 84% of surveyed patients used analgesics. Among the analgesics-taking respondents the most popular are acetaminophen (77%), ibuprofen (29%) and acetylsalicylic acid (23%). 73% of them takes one dose on short-term, but 1% takes the several of doses per day. 17% of respondents believe that these drugs do not have side effects and only affect the source of pain, and 33.5% were not able to determine it. More woman than man ( 48 vs 21 p=0,0027) were aware that analgesics have side effects. 50% of respondents believe that NSAIDs can cause kidney damage, but 27.6% would not bother symptoms such as high blood pressure and peripheral edema occurring over NSAIDs usage. One third of surveyed patients did not admit usage of NSAIDs during visit to the nephrologist. 74% of respondents read enclosed leaflet entirely. The pharmacist asked about any chronic illness in 32% of renal patients, but only in 21% of patients suggestion was made to take acetaminophen (as safer) than NSAIDs. Conclusions: The survey results indicate a low awareness of analgesics among renal patients, especially among men. Every second respondent would discontinue painkiller therapy due to side effects that indicate possible kidney damage, but only just over half of those people would visit the physician, which signify the insufficient knowledge about potential side effects of analgesics. The results directly mark the necessity of reliable, professional information for patients in an understandable manner about the possible health-important side effects and significant interactions for such a broadly available drugs. SP286SAFETY AND EFFICACY OF ECULIZUMAB IN ADULT PATIENTS WITH aHUS, WITH OR WITHOUT BASELINE DIALYSIS Fadi Fakhouri Fadi Fakhouri 1 Department of Nephrology and Umr 643, CHU de Nantes, Nantes, France Camille L. Bedrosian Camille L. Bedrosian 2 Alexion Pharmaceuticals, Inc., Cheshire, CT Masayo Ogawa Masayo Ogawa 2 Alexion Pharmaceuticals, Inc., Cheshire, CT John F. Kincaid John F. Kincaid 2 Alexion Pharmaceuticals, Inc., Cheshire, CT Chantal Loirat Chantal Loirat 3 Assistance Publique–Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France Abstract Introduction and Aims: Atypical hemolytic uremic syndrome (aHUS) is characterized by chronic, uncontrolled complement activation and TMA. Plasma exchange/infusion has been used historically to manage aHUS, but fails to prevent end-organ damage - 46% of adult patients (pts) with aHUS progress to ESRD after the first clinical manifestation. Eculizumab (ecu) inhibits terminal complement-mediated TMA and has been proven safe and effective in pts with aHUS, improving renal function and eliminating the need for dialysis in many pts. The objective of this analysis was to characterize the safety and efficacy of ecu in pts with dialysis (DIAL) and without dialysis (N-DIAL) at baseline (BL) in the largest prospective trial of adults with aHUS. Methods: A sub-analysis of an open-label, single-arm trial to evaluate safety and efficacy of ecu in pts with aHUS aged ≥18 years was performed. Primary study outcome was the proportion of pts who achieved complete TMA response during 26 wks of ecu tx. Pts were vaccinated against N. meningitidis. Inclusion criteria included platelet (plt) count <150 x 109/L, LDH ≥1.5 x ULN, and sCR ≥ULN. Exclusion criteria included pts with ADAMTS-13 deficiency (ADAMTS-13 activity <5%) and pts with Shiga-toxin-producing E. coli infection. Results: The table below lists BL characteristics and efficacy outcomes at Wk 26. Ecu significantly improved plt count (x109/L) in both DIAL (163.2, P<0.0001) and N-DIAL (87.4, P=0.0120) pts. eGFR (mL/min/1.73 m²) improved in DIAL (35.0, P<0.0001) and N-DIAL (20.0, P=0.0179) pts. Of BL DIAL pts, 20/24 (83%) discontinued dialysis, and none of these 20 pts needed to resume dialysis. Of BL N-DIAL pts, 4/17 (24%) started new dialysis and 15/17 (88%) were dialysis-free at Wk 26. The treatment-emergent adverse event profile was similar for both groups. Conclusions: Ecu resulted in significant and clinically meaningful improvements in hematologic and renal parameters in BL DIAL and N-DIAL pts with aHUS. Significant increases in both plt count and eGFR from BL were observed for DIAL and N-DIAL pts at Wk 26. Notably, more than 80% of pts on dialysis at BL were able to discontinue dialysis. A similar proportion of BL DIAL and N-DIAL pts were dialysis-free at Wk 26. This sub-analysis is consistent with previously reported data from a prior ecu trial in adolescent and adult pts whereby 80% of BL DIAL pts were able to discontinue dialysis by Wk 26, maintained through a median of 104 wks, and eGFR was significantly increased regardless of prior dialysis. Collectively, these data provide additional support that ecu is a proven, effective, and safe tx in adult pts with aHUS with or without a history of dialysis. Fig. 1 Open in new tabDownload slide Fig. 1 Open in new tabDownload slide SP287RELATIONSHIP BETWEEN ASYMMETRIC DIMETHYLARGININE(ADMA) PLASMA LEVEL, BIOCHEMICAL,ECHOCARDIOGRAPHIC PARAMETERS,INTIMA-MEDIA THICKNESS(IMT) AND BLOOD PRESSURE IN PATIENTS WITH NONDIABETIC PROTEINURIA Zbigniew Heleniak Zbigniew Heleniak 1 Department of Nephrology, Transplantology and Internal Medicine Medical University of GdańSk, GdańSk, Poland Ewa Aleksandrowicz Ewa Aleksandrowicz 2 Department of Clinical Nutrition Medical University of GdańSk, GdańSk, Poland Ewa ŚWierblewska Ewa ŚWierblewska 3 Department of Hypertension and Diabetology Medical University of GdańSk, GdańSk, Poland Katarzyna Kunicka Katarzyna Kunicka 3 Department of Hypertension and Diabetology Medical University of GdańSk, GdańSk, Poland Leszek Bieniaszewski Leszek Bieniaszewski 3 Department of Hypertension and Diabetology Medical University of GdańSk, GdańSk, Poland Zbigniew Zdrojewski Zbigniew Zdrojewski 4 Department of Internal Disease, Connective Tissue Disease and Geriatrics Medical University of GdańSk, GdańSk, Poland BolesłAw Rutkowski BolesłAw Rutkowski 1 Department of Nephrology, Transplantology and Internal Medicine Medical University of GdańSk, GdańSk, Poland Abstract Introduction and Aims: Endothelial dysfunction due to reduced availability of nitric oxide (NO) is an early step in the atherosclerotic vascular disease. NO is synthesized from amino acid L-arginine via the action of NO synthase, which is blocked by endogenous inhibitor the asymmetric dimethylarginine (ADMA). ADMA is naturally occurring amino acid found in plasma and various types of tissues. The plasma level of ADMA is reported to be associated with cardiovascular risk factors such as hypertension, diabetes and chronic renal disease.The aim of this study was estimation the relationship between ADMA plasma level, biochemical, echocardiographic parameters, IMT and blood pressure in patients with nondiabetic proteinuria. after 6 and 12 months period of treatment using ACE inhibitors, sartans, statins, steroids, cylcophosphamide Methods: Thirty seven patients (11F, 26M) in mean age 38,5 years old with non-diabetic proteinuria were enrolled to the study. Diabetes and coronary disease weren't diagnosed in these patients. Treatment schedule (ACE inhibitors, sartans, steroids, cyclophosphamid or cyclosporine) was adjusted according medical indications. ADMA plasma level, biochemical, echocardiographic parameters, IMT and blood pressure were assessed at the 0 month and after 6 and 12 months Results: Results are presented in the table 1 and 2.There was statistically significant change in level of ADMA, TCH, triglycerides, albumin, fibrinogen and daily urinary protein loss during 12 months of treatment. There weren’t statistically significant change in creatinine level. There were only statistically significant relationship between ADMA level and CRP, fibrinogen and TCH (p<0,05), but non-statically between ADMA and other biochemical parameters, echocardiographic parameters, and blood pressure Conclusions: ADMA concentration decreased significantly during the treatment period.The correlation of ADMA with single biochemical parameters were statistically significant.There was no treatment influence on echocardiographic parameters, IMT and blood pressure and these parameters didn’t correlate with ADMA Table 1 Average value of biochemical, echocardiographic parameters, blood pressure and IMT Parameter . 0 month . 6 month . 12 month . P . CRP mg/l 1,66 1,26 1,19 ns Albumin g/dl 37,13 42,88 41,23 <0,001 Fibrinogen g/l 4,93 3,83 3,79 <0,001 Creatinine mg/dl 1,14 1,17 1,15 ns TCH mg/dl 285,24 219,00 210,79 <0,001 Triglicerydes mg/dl 238,81 195,73 154,53 <0,001 Daily urinary protein loss g 4,13 1,76 1,55 <0,001 ADMA umol/l 0,77 0,56 0,40 <0,001 LVMI g/m2 224,36 243,54 254,53 <0,001 EF% 64,88 62,49 61,85 ns E/A 1,20 1,25 1,34 ns E/è 3,51 3,83 3,93 ns SBP mmHg 121,8 126,1 124,1 ns DBP mmHg 75,6 76,2 78,1 ns IMT mm 0,60 0,59 0,57 ns Parameter . 0 month . 6 month . 12 month . P . CRP mg/l 1,66 1,26 1,19 ns Albumin g/dl 37,13 42,88 41,23 <0,001 Fibrinogen g/l 4,93 3,83 3,79 <0,001 Creatinine mg/dl 1,14 1,17 1,15 ns TCH mg/dl 285,24 219,00 210,79 <0,001 Triglicerydes mg/dl 238,81 195,73 154,53 <0,001 Daily urinary protein loss g 4,13 1,76 1,55 <0,001 ADMA umol/l 0,77 0,56 0,40 <0,001 LVMI g/m2 224,36 243,54 254,53 <0,001 EF% 64,88 62,49 61,85 ns E/A 1,20 1,25 1,34 ns E/è 3,51 3,83 3,93 ns SBP mmHg 121,8 126,1 124,1 ns DBP mmHg 75,6 76,2 78,1 ns IMT mm 0,60 0,59 0,57 ns Table 1 Average value of biochemical, echocardiographic parameters, blood pressure and IMT Parameter . 0 month . 6 month . 12 month . P . CRP mg/l 1,66 1,26 1,19 ns Albumin g/dl 37,13 42,88 41,23 <0,001 Fibrinogen g/l 4,93 3,83 3,79 <0,001 Creatinine mg/dl 1,14 1,17 1,15 ns TCH mg/dl 285,24 219,00 210,79 <0,001 Triglicerydes mg/dl 238,81 195,73 154,53 <0,001 Daily urinary protein loss g 4,13 1,76 1,55 <0,001 ADMA umol/l 0,77 0,56 0,40 <0,001 LVMI g/m2 224,36 243,54 254,53 <0,001 EF% 64,88 62,49 61,85 ns E/A 1,20 1,25 1,34 ns E/è 3,51 3,83 3,93 ns SBP mmHg 121,8 126,1 124,1 ns DBP mmHg 75,6 76,2 78,1 ns IMT mm 0,60 0,59 0,57 ns Parameter . 0 month . 6 month . 12 month . P . CRP mg/l 1,66 1,26 1,19 ns Albumin g/dl 37,13 42,88 41,23 <0,001 Fibrinogen g/l 4,93 3,83 3,79 <0,001 Creatinine mg/dl 1,14 1,17 1,15 ns TCH mg/dl 285,24 219,00 210,79 <0,001 Triglicerydes mg/dl 238,81 195,73 154,53 <0,001 Daily urinary protein loss g 4,13 1,76 1,55 <0,001 ADMA umol/l 0,77 0,56 0,40 <0,001 LVMI g/m2 224,36 243,54 254,53 <0,001 EF% 64,88 62,49 61,85 ns E/A 1,20 1,25 1,34 ns E/è 3,51 3,83 3,93 ns SBP mmHg 121,8 126,1 124,1 ns DBP mmHg 75,6 76,2 78,1 ns IMT mm 0,60 0,59 0,57 ns Table 2 Evaluation the relationship between plasma ADMA and parameters in the study group parameter . r . p . Age -0,119 ns gender 0,980 ns hypertension -0,323 ns SBP -0,016 ns DBP 0,027 ns CRP 0,266 <0,05 Albumin -0,002 ns Fibrynogen 0,402 <0,05 Creatinine 0,170 ns TCH 0,341 <0,05 Trigicerides 0,134 ns Daily urinary protein loss 0,245 ns LVMI 0,018 ns EF 0,111 ns E/A -0,032 ns E/e’ -0,032 ns parameter . r . p . Age -0,119 ns gender 0,980 ns hypertension -0,323 ns SBP -0,016 ns DBP 0,027 ns CRP 0,266 <0,05 Albumin -0,002 ns Fibrynogen 0,402 <0,05 Creatinine 0,170 ns TCH 0,341 <0,05 Trigicerides 0,134 ns Daily urinary protein loss 0,245 ns LVMI 0,018 ns EF 0,111 ns E/A -0,032 ns E/e’ -0,032 ns Table 2 Evaluation the relationship between plasma ADMA and parameters in the study group parameter . r . p . Age -0,119 ns gender 0,980 ns hypertension -0,323 ns SBP -0,016 ns DBP 0,027 ns CRP 0,266 <0,05 Albumin -0,002 ns Fibrynogen 0,402 <0,05 Creatinine 0,170 ns TCH 0,341 <0,05 Trigicerides 0,134 ns Daily urinary protein loss 0,245 ns LVMI 0,018 ns EF 0,111 ns E/A -0,032 ns E/e’ -0,032 ns parameter . r . p . Age -0,119 ns gender 0,980 ns hypertension -0,323 ns SBP -0,016 ns DBP 0,027 ns CRP 0,266 <0,05 Albumin -0,002 ns Fibrynogen 0,402 <0,05 Creatinine 0,170 ns TCH 0,341 <0,05 Trigicerides 0,134 ns Daily urinary protein loss 0,245 ns LVMI 0,018 ns EF 0,111 ns E/A -0,032 ns E/e’ -0,032 ns © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
TI - CKD PATHOPHYSIOLOGY AND CLINICAL STUDIES
JF - Nephrology Dialysis Transplantation
DO - 10.1093/ndt/gfu148
DA - 2014-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/ckd-pathophysiology-and-clinical-studies-rT9UOeCZCp
SP - iii148
EP - iii167
VL - 29
IS - suppl_3
DP - DeepDyve
ER -