TY - JOUR
AB - MP320INTERSTITIAL INFLAMMATION AND LONG - TERM RENAL OUTCOMES IN LUPUS NEPHRITIS Daniela Monova Daniela Monova 1 Medical Institute - Ministry of Interior, Sofia, Bulgaria Simeon Monov Simeon Monov 2 Medical University, Sofia, Bulgaria Todor Todorov Todor Todorov 2 Medical University, Sofia, Bulgaria Abstract Introduction and Aims: The International Society of Nephrology/Renal Pathology Society (ISN/RPS) pathological classification criteria of lupus nephritis are limited to glomerular injury. Although the tubulointerstitium is commonly involved, the importance of such involvement is not well defined. The major objective of this study was to evaluate the association of interstitial inflammation with the long-term outcomes of patients with lupus nephritis. Methods: A total of 289 patients who were diagnosed with lupus nephritis between 1984 and 2013 were analyzed. The follow-up data were obtained, and the analysis was conducted to determine the effect of interstitial inflammation on the rate of the doubling of serum creatinine or end-stage renal disease (ESRD) in patients with lupus nephritis. Of the patients included in the cohort, 49 underwent a second biopsy. Results: The degree of interstitial inflammation was positively correlated with the serum creatinine level at the time of biopsy (p<0,001) but not at the end of the follow-up period (p>0,5). The complements level, anti-dsDNA, ANA, and proteinuria were not related to the degree of interstitial inflammation. There was no relationship between the probability of remission and the severity of interstitial infiltrate. The rate of no remission was 40% among those without interstitial infiltrate, 34,9% in those with mild infiltrate and 23,2% among those with moderate-to-severe infiltrate. There was no relationship between interstitial inflammation at the baseline biopsy and worsening of renal function. There was a strong relationship between interstitial inflammation at the repeat biopsy and renal survival (p<0,001). The recovery of interstitial inflammation in lupus nephritis correlated with a favorable outcome in the patients with interstitial inflammation at baseline that had resolved at the repeated biopsy. Conclusions: The persistence of interstitial inflammation is associated with poor renal outcome among patients with lupus nephritis. A comprehensive histological assessment of inflammation in lupus nephritis including interstitial inflammation may provide better prognostic information. MP321NEUTROPHILS FROM PATIENTS WITH ANCA-ASSOCIATED VASCULITIS EXHIBIT AN INCREASED PROPENSITY TO UNDERGO NEUTROPHIL EXTRACELLULAR TRAP (NET) FORMATION AND/OR NECROSIS Daniel Söderberg Daniel Söderberg 1 Linköping University, Linköping, Sweden Tino Kurz Tino Kurz 1 Linköping University, Linköping, Sweden Maria Weiner Maria Weiner 1 Linköping University, Linköping, Sweden 2 County Council of Östergötland, Linköping, Sweden Per Eriksson Per Eriksson 1 Linköping University, Linköping, Sweden 2 County Council of Östergötland, Linköping, Sweden Mårten Segelmark Mårten Segelmark 1 Linköping University, Linköping, Sweden 2 County Council of Östergötland, Linköping, Sweden Abstract Introduction and Aims: Dying neutrophils surrounding small vessels is a histological hallmark of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (=ANCA). These dying neutrophils may provide the source of antigens for the generation of ANCA. We have previously shown that neutrophils in ANCA-associated vasculitis (AAV) patients in remission are less prone to undergo cell death from apoptosis. Recently, a new pathway for programmed cell death named NET-osis was described. Interestingly, neutrophil extracellular traps (NETs), which are released during NETosis, have been visualized at the site of vasculitic lesions, and have been suggested to be important in a rodent model of drug-induced vasculitis. In this study we examined the propensity of neutrophils from AAV patients to undergo NET formation and/or necrosis in vitro. Methods: Peripheral whole blood was drawn from 22 AAV patients (4 active/18 remission), 9 males/13 females, median age 67.5 years) and 15 healthy controls (HC) (6 males/9 females, median age 57 years) into EDTA-treated tubes and neutrophils were isolated by Percoll density gradient centrifugation. The neutrophils were exposed for 4 h to 10 nM Phorbol 12-myristate 13-acetate (PMA), 2 or 8 ng/ml TNF-α or left untreated. Neutrophils from a sample subset (5 patients, 10 HC) were also pre-incubated for 1 h with 0, 10 or 100 nM dexamethasone (Dex) prior to 4 h PMA treatment. DNA was quantified hourly in a microplate fluorescence reader using the cell-impermeable dye Sytox Green and the results were expressed as percentage of total DNA (lysis with 1% Triton X-100). Neutrophil cell death was also visualized by fluorescence microscopy. Results: When stimulated with PMA, neutrophils from both AAV patients and HC underwent NET-osis efficiently. Even when using a moderate dose of PMA (10 nM) no difference was seen between patients and HC. However, unstimulated neutrophils of AAV patients showed an increased propensity for cell death after 4 h compared to HC (p<0.05, see figure).This was found also when the analysis was limited to patients in stable remission. Stimulation of the neutrophils with a high dose of TNF-α (8 ng/ml) abolished the difference in cell death between patients and controls, while a difference could still be detected after co-incubation with a low TNF-α dose (2 ng/ml). Incubation with Dex also influenced the in vitro cell death. A high dose of Dex (100 nM) decreased PMA-induced NET-osis/necrosis while it increased spontaneous cell death, at least in neutrophils of HC. Conclusions: Neutrophils from AAV patients show an increased propensity for spontaneous NET formation and/or necrosis in vitro. However, these differences can be reversed by the addition of inflammatory cytokines (i.e. TNF-α) and high doses of anti-inflammatory drugs (i.e. Dex). Further and more intricate studies are needed to reveal the significance of these findings. Open in new tabDownload slide Open in new tabDownload slide MP322GENDER-DEPENDENT DIFFERENCES IN CLINICAL COURSE OF LUPUS NEPHRITIS. Katarzyna Jakuszko Katarzyna Jakuszko 1 Wroclaw Medical University, Wroclaw, Poland Agata Sebastian Agata Sebastian 1 Wroclaw Medical University, Wroclaw, Poland Zofia Bednarz Zofia Bednarz 1 Wroclaw Medical University, Wroclaw, Poland Magdalena Krajewska Magdalena Krajewska 1 Wroclaw Medical University, Wroclaw, Poland Piotr Wiland Piotr Wiland 1 Wroclaw Medical University, Wroclaw, Poland Katarzyna Madziarska Katarzyna Madziarska 1 Wroclaw Medical University, Wroclaw, Poland Waclaw Weyde Waclaw Weyde 1 Wroclaw Medical University, Wroclaw, Poland 2 Faculty of Dentistry, Wroclaw Medical University, Wroclaw, Poland Marian Klinger Marian Klinger 1 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction and Aims: Genetic, environmental and hormonal factors are involved in the pathogenesis of systemic lupus erythematosus (SLE). The female sex hormones have a well known impact on the incidence of SLE, diagnosed most often in women of childbearing potential. The course of the disease differs in both genders, with more severe symptoms of lupus nephritis (LN) and more rapid progression to end stage renal disease in male patients, however findings are not entirely consistent. The aim of the study was to confirm the influence of gender on the course LN in our cohort of patients. Methods: A retrospective study was conducted on 114 patients (pts) with diagnosed LN and 55 pts with SLE without renal involvement, including 147 women (87.0%) and 22 men (13.0%). Patients were evaluated with the presence of clinical manifestations of SLE based on American College of Rheumatology (ACR) and Systemic Lupus International Collaborative Clinics (SLICC) diagnostic criteria, the course of disease, immunological and clinical biomarkers of the disease activity. The disease activity was estimated by SLE Disease Activity Index (SLEDAI) and isolated features of renal involvement (rSLEDAI). Results: There were no differences between the number of fulfilled diagnostic criteria according to gender - the average number of ACR was in female pts 5.48±1.46 and in male pts 5.14±1.25 (p=0.35), SLICC 6.05±1.83 vs 5.91±1.6 (p=0.92). Renal involvement occurred significantly more often in the group of male pts than in female (86.4% vs 64.6%, p=0.03) and skin lesions in female (81.6% vs 54.5%, p=0.007). In 50% of men and 44,2% of women LN was diagnosed as a first manifestation of SLE. In the remaining group the symptoms of renal involvement appeared earlier in male pts than in female pts (3.9±3.1 years, range 1-10 vs 5.4±4.9 years, range 1-21, p=0.026, Fig.1). In the group of 31.6% of male pts and 14.7% of female pts the progression of kidney disease, defined as doubling of serum creatinine or the necessity of renal replacement therapy, was observed, however the differences were not statistically significant (p=0.065, Fig.2).The clinical indicators of the activity of LN were significantly higher in men than in women (proteinuria 283.6±426.9 vs 166.0±279.5 mg/dl, p=0.048; creatinine 1.44±0,46 vs 1.25±0.64 mg/dl, p=0.0002; and uremic acid 7.74±1.28 mg/dl vs 5.93±1.85, p<0.0001). However no differences in the activity of SLE and LN assessed by SLEDAI and rSLEDAI in both genders were found. SLEDAI in the group of women was 13.2±7.1, in men 15.0±8.2 (p=0.18), rSLEDAI 5.9±4.9 vs 7.3±4.9 (p=0.08). Conclusions: The study proved the statistically significant higher prevalence and severity of lupus nephritis in male patients. Figure 1 Open in new tabDownload slide Gender-dependent differences in LN-free survival Figure 1 Open in new tabDownload slide Gender-dependent differences in LN-free survival Figure 2 Open in new tabDownload slide Gender-dependent differences in renal survival Figure 2 Open in new tabDownload slide Gender-dependent differences in renal survival MP323RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN): EPIDEMIOLOGY, OVERALL AND DISEASE SPECIFIC OUTCOMES IN A TERTIARY CENTRE IN CAPE TOWN SOUTH AFRICA Jashira Naidoo Jashira Naidoo 1 University Cape Town, Cape Town, South Africa Nicola Wearne Nicola Wearne 2 University of Cape Town, Cape Town, South Africa Erika Jones Erika Jones 2 University of Cape Town, Cape Town, South Africa Charles Swanepoel Charles Swanepoel 2 University of Cape Town, Cape Town, South Africa Brian Rayner Brian Rayner 2 University of Cape Town, Cape Town, South Africa Ikechi Okpechi Ikechi Okpechi 2 University of Cape Town, Cape Town, South Africa Abstract Introduction and Aims: Rapidly progressive glomerulonephritis (RPGN) may be a common cause of chronic kidney disease (CKD) in many developing countries of Sub-Saharan Africa (SSA). Due to the often unavailability of diagnostic and treatment facilities, the epidemiology of RPGN has not been sufficiently studied in SSA. The aim of this study is to describe the epidemiology and outcomes of patients with RPGN in a single centre in Cape Town South Africa. Methods: This 7 year retrospective study (1ST January 2006 TO 31st December 2012) was approved by the Research Ethics Committee of the University of Cape Town. Records of patients with biopsy proven RPGN were included for analysis. A composite outcome of end-stage renal disease (ESRD) or death was chosen. Results: In this study, 61.4% of all the patients (81/132) were females and the overall age at time of biopsy was 33.4 ± 14.1 years. Patients of mixed ancestry made up 59.8% of the participants with patients of black and white ancestry making up 35.6% and 4.5% respectively of the patients. Lupus nephritis accounted for 49.2% of all cases of RPGN presenting within the study period. The remaining causes of RPGN were idiopathic mesangiocapillary GN (15.2%), primary crescentic GN (11.4%), pauci-immune GN (9.8%), post-infectious GN (7.6%) and others such as IGA nephropathy, HIV - associated nephropathy, Goodpasture’s disease and membranous GN associated with crescents accounting for the other 6.8%. The average number of glomeruli per biopsy was 15.1 ± 8.2 and 15.9% were reported with moderate or severe interstitial fibrosis at biopsy. Seventy seven patients (58.3%) were reported with less than 50% crescents on their biopsy. There were 34 deaths (25.8%) and 24 patients (18.2%) had ESRD. The composite endpoint was reached by 37.9% of the subjects. Overall, the 1-year, 2-year and 5-year survival of the composite end point was 68.4%, 64.3% and 49.4% respectively (see figure 1). The 5-year survival of patients with lupus nephritis, MCGN, pauci-immune GN, primary crescentic GN and PIGN was 67.8%, 19.2%, 29.9%, 22.2% and 39.4% respectively. Open in new tabDownload slide Open in new tabDownload slide . Conclusions: Lupus nephritis is the commonest cause of RPGN in Cape Town and the overall 5 year survival of patients with RPGN was poor at 49.4%. There is need for prospective studies to possibly improve the outcome of patients with RPGN in developing countries. MP324ASSOCIATION OF GLOMERULAR MACROPHAGE PHENOTYPES AND URINE SOLUBLE CD163 WITH DISEASE ACTIVITY IN HUMAN LUPUS NEPHRITIS Nobuhide Endo Nobuhide Endo 1 Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan Naotake Tsuboi Naotake Tsuboi 1 Nagoya University Graduate School of Medicine, Nagoya, Japan Kazuhiro Furuhashi Kazuhiro Furuhashi 1 Nagoya University Graduate School of Medicine, Nagoya, Japan Seiichi Matsuo Seiichi Matsuo 1 Nagoya University Graduate School of Medicine, Nagoya, Japan Shoichi Maruyama Shoichi Maruyama 1 Nagoya University Graduate School of Medicine, Nagoya, Japan Abstract Introduction and Aims: Glomerular cell proliferation, in particular leukocytes and mesangial cells, is a hallmark of lupus nephritis. Among glomerular leukocyte subsets, recent studies exploring lupus nephritis suggest an active role of macrophages in mediating renal inflammation and Injury. In addition to the effector roles of classically activated macrophages for tissue injury, recent studies have shown that alternatively activated (M2) macrophages are involved in resolution of inflammation in animal models of kidney disease. But, clinical relevance of M2 macrophage in human disease is largely unknown. The current study aimed to evaluate renal accumulation of macrophage phenotypes in human lupus nephritis (LN) and significance of soluble form of CD163 (sCD163), a representative marker for M2 cells, for LN disease activity. Methods: Plasma, urine and kidney biopsy samples were obtained from 74 patients with LN. Histological features were classified according to the ISN/RPS LN criteria. Immunohistochemical analyses using anti-human CD68, CD163 or CD204 antibodies were performed for identification of macrophage phenotypes. Concentrations sCD163, MCP-1 and NGAL in plasma and urine were measured by ELISA. Results: Immunohistological analysis in LN glomeluli revealed more than 70% of CD68+ macrophages was merged with CD163+ cells and more than 90% of CD163+ cells was merged with CD68+ cells. However, CD163+ cells appeared to be more than CD68+ cells in interstitum, indicating the different origin of glomerular and interstitial CD163+ macophages. The cell counts of glomerular CD68+, CD163+ or CD204+ macrophages were increased in association with severity of biopsy active index (BAI) score in LN. Interstitial CD68+, CD163+ or CD204+ macrophage infiltration correlated with eGFR. Urine sCD163 level showed stronger correlation with the number of glomerular CD163 positive cell counts (r=0.501) and BAI score (r=0.644) than plasma sCD163 levels with both of the above (r=0.289 and r=0.295, respectively). Correlation of urine sCD163 with BAI was comparable to that of urine MCP-1 levels (r=0.592) and was much better than NGAL (r=0.174) in LN. Conclusions: These results suggest that CD163+ or CD204+ macrophage is the dominant phenotype in kidneys of LN patients, and urine sCD163 level has a potential significance for estimation of disease activity in human LN. MP325THE “DOUBLE POSITIVE” DISEASE: A PARTICULARLY SEVERE FORM OF SYSTEMIC VASCULITIS. Maëva Clerté Maëva Clerté 1 Hopital Europeen George Pompidou, Paris, France Charlène Levi Charlène Levi 1 Hopital Europeen George Pompidou, Paris, France Maxime Touzot Maxime Touzot 2 Centre Hospitalier Universitaire de Nantes, Nantes, France Fadi Fakhouri Fadi Fakhouri 2 Centre Hospitalier Universitaire de Nantes, Nantes, France Catherine Monge Catherine Monge 3 Centre Hospitalier Intercommunal de Poissy-St-Germain, Poissy, France Céline Lebas Céline Lebas 4 Centre Hospitalier de Valenciennes, Valenciennes, France Imad Abboud Imad Abboud 5 Hôpital Saint Louis, Paris, France Antoine Huart Antoine Huart 6 Centre Hospitalier Universitaire Rangueil, Toulouse, France Philippe Durieux Philippe Durieux 7 Centre Hospitalier de Wallonie Picarde, Tournai, Belgium Emmanuelle Charlin Emmanuelle Charlin 8 Hôpitaux Universitaires de Strasbourg, Strasbourg, France Eric Thervet Eric Thervet 1 Hopital Europeen George Pompidou, Paris, France Alexandre Karras Alexandre Karras 1 Hopital Europeen George Pompidou, Paris, France Abstract Introduction and Aims: The “double positive” disease is a rare systemic vasculitis characterized by the presence of both antineutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane antibodies (anti-GBM). The aim of this study was to describe the clinical presentation and the renal prognosis of this entity, in which there is no consensual treatment. Methods: We conducted a retrospective study among 8 different nephrology centers in France and Belgium. Data on demographics, clinical presentation, histology and treatment were obtained by chart review. Results: Ten patients have been included to date. The sex ratio (M/F) was 6/4, the median age at the diagnosis was 76.2 years. Six patients had general symptoms such as fever, weight loss, muscular and/or articular signs. All patients had a marked inflammatory syndrome (mean CRP 118 mg/L) and anemia was constant (mean Hb level 9.2 g/dl). Six patients had pulmonary manifestations such as hemoptysis and dyspnea due to intra-alveolar hemorrhage but only one required mechanical ventilation. All patients presented with rapidly progressive glomerulonephritis, combining acute renal failure, proteinuria (from 0.9 to 26 g/L) and hematuria (microscopic for 9 patients). The mean serum creatinine at diagnosis was 901 µmol/l. Nine patients started dialysis immediately after diagnosis. Renal histology showed crescentic glomerulonephritis and linear immunofluorescence along the glomerular basement membrane. Nine patients had detectable serum anti-GBM antibody and all of them had detectable ANCA. Specificity of ANCA was anti-PR3 in 2 cases, anti-MPO in 8. Except one patient who did not receive any immunosuppressive therapy, all the others were treated according to the local protocol (corticosteroids, oral or intravenous cyclophosphamide, plasma exchange). None of the dialysis-depending patients had recovery of his renal function. Only one patient had a relapse of the systemic vasculitis. Conclusions: The double positive disease shares several clinical characteristics, such as general and extra-renal symptoms, with ANCA-associated vasculitis while its renal manifestations, severity and prognosis is particularly severe, quite similar to what has been described in anti-GBM disease. MP326THE RELATIONSHIP BETWEEN SERUM C1Q AND ANTI-C1Q ANTIBODIES IN PATIENTS WITH LUPUS NEPHRITIS Katarzyna Smykal-Jankowiak Katarzyna Smykal-Jankowiak 1 University of Medical Sciences, Poznan, Poland Zofia I Niemir Zofia I Niemir 1 University of Medical Sciences, Poznan, Poland Magdalena Polcyn-Adamczak Magdalena Polcyn-Adamczak 1 University of Medical Sciences, Poznan, Poland Abstract Introduction and Aims: The congenital C1q deficiency is the predisposing factor for the development of systemic lupus erythematosus (SLE). However, a close relationship between the serum levels of C1q and the occurrence of anti-C1q Abs has been suggested, particularly in patients with lupus nephritis (LN). Therefore, we assessed the serum concentrations of C1q and anti-C1q Abs in patients with LN and compared these results with those obtained in healthy controls (C). Methods: The study involved 63 patients with LN and 79 C. The SLE activity was scored using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K). Forty-one patients presented with active LN (aLN), whereas the remaining 22 patients were in inactive phase of the disease (inLN). Serum levels of C1q, anti-C1q and anti-dsDNA Abs were determined by standardized enzyme-linked immunosorbent assays. Results: The median values of serum C1q were 279.6 (134.2 - 442.7) ng/ml in LN and 270.9 (151.9 - 570.2) ng/ml in C. Anti-C1q Abs were detected in 66.7% of patients with LN and in 8.9% of C (p<0.0001). In LN, a significant negative correlation between the C1q and anti-C1q levels (r=-0.38; p<0.005) was observed. In addition, positive correlations between both anti-C1q and anti-dsDNA Abs and the SLEDAI-2K score were found (r=0.48 and r=0.5, respectively; p<0.0001 for both). Apart from this, haematuria and the nephrotic syndrome occurred significantly more often in the anti-C1q positive LN (p<0.005 and p<0.05, respectively).The prevalence of these Abs was significantly higher in aLN than inLN (82.9% v. 36.4%, p<0.0001). It was also true for serum concentrations of anti-C1q Abs (p<0.0001). After all patients’ arrangement into C1q quartiles, 27% of them were allocated to the first quartile, 20.6% to the second quartile, 38.1% to the third quartile and only 14.3% to the fourth quartile (p<0.05). Anti-C1q Abs were detected, respectively, in 94.1%, 69.2%, 54.2%, and 44.4% of patients from the first, second, third and fourth quartile (p<0.005). Interestingly, a decrease in GFR below 60 ml/min/1.73m2 in the last month was observed, respectively, in 23.5% and 15.4% of patients from the first and second quartile, compared to 4.2% and 0% of those from the third and fourth quartile (p<0.05). Conclusions: Our results confirmed the suggested link between the C1q usage and anti-C1q Abs formation in LN. Of interest, this association seems to contribute to the worsening of renal function. MP327AN EPIDEMIOLOGICAL STUDY ANALYSING SURVIVAL RATES AMONGST ANCA NEGATIVE PATIENTS Steven Whatmough Steven Whatmough 1 Lancashire Teaching Hospitals, Preston, United Kingdom Niamh Sweeney Niamh Sweeney 1 Lancashire Teaching Hospitals, Preston, United Kingdom Sophie Fernandez Sophie Fernandez 1 Lancashire Teaching Hospitals, Preston, United Kingdom Memuna Hussain Memuna Hussain 1 Lancashire Teaching Hospitals, Preston, United Kingdom Ajay Dhaygude Ajay Dhaygude 1 Lancashire Teaching Hospitals, Preston, United Kingdom Abstract Introduction and Aims: The introduction of ANCA assays has improved the diagnosis of small vessel vasculitis (SVV). Literature suggests that approximately 10% of patients with pauci-immune glomerulonephritis (PIGN) are ANCA negative1. Information regarding outcomes of ANCA negative patients is limited2. In this study, we retrospectively analysed outcomes of ANCA negative patients. Methods: All the patients diagnosed with PIGN, within a regional centre, between 1988 and 2010 were included in this study. Renal and patient survival outcomes were compared between those with ANCA positive and ANCA negative SVV. Furthermore, the cumulative cyclophosphamide (CYP) doses, for each ANCA status, were calculated. Results: A total of 314 patients were identified, of which 238 patients had a recorded ANCA status. Overall, 163 (68%) patients were ANCA positive and 75 (32%) were ANCA negative. ANCA negative patients were younger and had a poorer renal survival (Figure-1). The results are presented in table-1. Table-1. A summary of patient demographics, patient/renal survival rates and the CYP dose. . Age at Diagnosis (Years) . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average CYP Dose (mg) . 5 Years . 10 Years . 5 Years . 10 Years . ANCA Positive 60 483.62 70% 52% 59% 41% 4231 ANCA Negative 50 527.04 66% 52% 43% 30% 3469 P Value <0.0001 0.4418 0.5026 0.5488 0.0261 0.0352 0.2935 . Age at Diagnosis (Years) . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average CYP Dose (mg) . 5 Years . 10 Years . 5 Years . 10 Years . ANCA Positive 60 483.62 70% 52% 59% 41% 4231 ANCA Negative 50 527.04 66% 52% 43% 30% 3469 P Value <0.0001 0.4418 0.5026 0.5488 0.0261 0.0352 0.2935 Table-1. A summary of patient demographics, patient/renal survival rates and the CYP dose. . Age at Diagnosis (Years) . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average CYP Dose (mg) . 5 Years . 10 Years . 5 Years . 10 Years . ANCA Positive 60 483.62 70% 52% 59% 41% 4231 ANCA Negative 50 527.04 66% 52% 43% 30% 3469 P Value <0.0001 0.4418 0.5026 0.5488 0.0261 0.0352 0.2935 . Age at Diagnosis (Years) . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average CYP Dose (mg) . 5 Years . 10 Years . 5 Years . 10 Years . ANCA Positive 60 483.62 70% 52% 59% 41% 4231 ANCA Negative 50 527.04 66% 52% 43% 30% 3469 P Value <0.0001 0.4418 0.5026 0.5488 0.0261 0.0352 0.2935 Open in new tabDownload slide Open in new tabDownload slide Conclusions: Our study suggests,1. ANCA negative patients present earlier in life than their ANCA positive counterparts.2. ANCA negative vasculitis has a noticeably higher incidence in the regional centre studied, when compared to current literature1.3. Despite a similar standard of immunosuppressive treatment, ANCA negative patients have a poorer long-term renal survival. Limitations: Data regarding organ involvement, relapses and plasma exchange treatment was not collected. References: 1. Min Chen, Feng Yu, Su-Xia Wang, et al: Antineutrophil Cytoplasmic Autoantibody-Negative Pauci-immune Crescentic Glomerulonephritis. J Am Soc Nephrol 18: 599-605, 2007. 2. Eisenberger U, Fakhouri F, Vanhille P, Beaufils H, Mahr A, Guillevin L, Lesavre P, Noel LH: ANCA-negative pauci immune renal vasculitis: Histology and outcome. Nephrol Dial Transplant 20: 1392-1399, 2005 MP328BILIRUBIN AS AN ADITIONAL BIOMARKER OF ACTIVE LUPUS? Katarzyna Jakuszko Katarzyna Jakuszko 1 Wroclaw Medical University, Wroclaw, Poland Zofia Bednarz Zofia Bednarz 1 Wroclaw Medical University, Wroclaw, Poland Agata Sebastian Agata Sebastian 1 Wroclaw Medical University, Wroclaw, Poland Magdalena Krajewska Magdalena Krajewska 1 Wroclaw Medical University, Wroclaw, Poland Katarzyna Gniewek Katarzyna Gniewek 1 Wroclaw Medical University, Wroclaw, Poland Piotr Wiland Piotr Wiland 1 Wroclaw Medical University, Wroclaw, Poland Waclaw Weyde Waclaw Weyde 1 Wroclaw Medical University, Wroclaw, Poland 2 Faculty of Dentistry, Wroclaw Medical University, Wroclaw, Poland Marian Klinger Marian Klinger 1 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction and Aims: Oxidative stress and modification of self-antigens may trigger autoimmunity and play an important role in the development and progression of systemic lupus erythematosus (SLE). Bilirubin, which is the breakdown product of heme catabolism, has an important antioxidant role. In recent studies higher protein oxidation in patients (pts) with active SLE and the relationship between low bilirubin concentrations and the prevalence of autoimmune diseases had been shown. The aim of the study was to verify the association between bilirubin levels and the clinical activity of SLE and lupus nephritis (LN) in our cohort of patients. Methods: The study included 180 pts diagnosed with SLE and a control group of 69 pts with primary glomerulonephritis (GN). A subset of 37 pts with SLE and severe anemia (n=4), diagnosed liver disease (n=18) or elevated levels of transaminases (n=15) were excluded from the study to eliminate the possible confounding effects on the serum bilirubin levels. In the remaining group of 143 pts with SLE the total of 254 samples were analyzed, with the average number of 2.1±1.4 (range 1-7). Bilirubin and the classical biomarkers of SLE activity, such as antinuclear antibodies (ANA), complement hemolytic activity (CH50), erythrocyte sedimentation rate (ESR), serum creatinine, protein, albumin and daily proteinuria were measured using commercially available tests. The disease activity was estimated by SLE Disease Activity Index (SLEDAI) and isolated features of renal involvement (rSLEDAI). Results: Lower concentrations of serum bilirubin occurred in blood samples from patients with more active disease assessed by SLEDAI for ≥13 points (0-12: 0.54±0.25 mg/dl, ≥13: 0.43±0.2 mg/dl, p=0.0003, Fig.1) and rSLEDAI for ≥8 points (0-4: 0.56±0.24 mg/dl; ≥8: 0.42± 0.22 mg/dl, p<0.0001). Moreover lower concentrations of bilirubin were characteristic for patients with renal involvement as a manifestation of SLE (0.47±0.24mg/dl) compared to pts with non-renal lupus (0.58±0.19mg/dl, p=0.003) and primary GN (0.58±0.3 mg/dl, p=0.005, Fig.2).Significant correlations between bilirubin concentrations and classical indicators of SLE activity were found-positive with CH50 (r=0.17, p=0.02) and negative with SLEDAI (r=-0.3, p<0.0001) rSLEDAI (r=-0.3, p<0.0001) and with ESR (r=-0.25, p=0.004). Moreover there were significant relationships between bilirubin concentrations and clinical activity of nephritis, including positive with serum protein (r=0.39, p<0.0001), albumin levels (r=0.47, p<0.0001) and negative with daily proteinuria (r=-0.37, p<0.0001), total cholesterol (r=-0.34, p<0.0001) and triglycerides (r=-0.48, p<0.0001). Conclusions: The study showed the role of bilirubin as an additional, non-invasive biomarker of the systemic lupus and especially lupus nephritis activity, as assessed by the relationships with clinical indicators of nephrotic syndrome severity and rSLEDAI indices. Open in new tabDownload slide Open in new tabDownload slide MP329RENAL ANCA ASSOCIATED VASCULITIS (AAV) AND COMPLEMENT HYPERACTIVATION SIGNS: A PROSPECTIVE STUDY. Lucio Manenti Lucio Manenti 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Maria Letizia Urban Maria Letizia Urban 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Augusto Vaglio Augusto Vaglio 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Enrica Gintoli Enrica Gintoli 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Maricla Galletti Maricla Galletti 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Carlo Buzio Carlo Buzio 1 Azienda Ospedaliera Universitaria Di Parma, Parma, Italy Abstract Introduction and Aims: Studies in animal models suggest that complement activation is crucial in the pathogenesis of ANCA associated vasculitis (AAV); recently we revised retrospectively our renal vasculitis cases and we documented that serum C3 (sC3) consumption was prevalent in 50% of patients at admission. Moreover sC3, as a marker of alternative pathway (AP) hyperactivation, showed a worse renal prognosis.In this study we evaluated prospectively in our new renal AAV cases the presence of sC3 consumption at admission and its relationship with clinical presentation.A longitudinal evaluation of complement components was done to assess the effect of immunosoppression and vasculitis remission on complement overactivation. Methods: We examined our series of 16 consecutive patients diagnosed with kidney biopsy as having AAV between 2008 and 2013. Patients had a mean follow-up of 26 months. We evaluated complement status and signs of hemolysis (LDH, haptoglobin, platelets count). Results: One patient died. 8/16 patients had a reduction of serum C3 (< 90 mg/dl) at presentation while serum C4 was in the normal range in the whole group. Hemolysis was documented in 4/16 patients (25%) at admission; this group showed sC3 reduction as a whole. Patients with reduced sC3 had a persistent reduction over the time. Conclusions: Our preliminary data confirms that serum C3 consumption, as a consequence of AP hyperactivation, is documented in a large portion of acute renal AAV. sC3 reduction seems to relate with hemloysis appearance, and is unresponsive to immunosuppressive treatments. sC3 persistent reduction would be supported by an underlying prediposing pavulum of AP regulating genesAn early recognition of complement hyperactivation and of hemolysis in renal AAV patients may allow to a more appropriate management (i.e eculizumab) of these cases. MP330ANTI-C1Q ANTIBODIES AND DISEASE ACTIVITY IN PATIENTS WITH LUPUS NEPHRITIS Daniela Monova Daniela Monova 1 Medical Institute, Sofia, Bulgaria Simeon Monov Simeon Monov 2 Medical University, Sofia, Bulgaria Trenka Argirova Trenka Argirova 3 Sofia University, Sofia, Bulgaria Abstract Introduction and Aims: Anti-C1q autoantibodies have been described in patients with systemic lupus erythematosus (SLE) and their presence has been closely correlated with renal disease activity. The aim of this study is to assess if anti-C1q and other markers of disease activity are associated with nephritis according to renal BILAG score in a population of patients with SLE. Methods: SLE patients was grouped according to BILAG renal score: categories A+ B+ C (active nephritis), category D (inactive nephritis) and category E (no nephritis). Anti-C1q autoantibodies were determined by ELISA with duplicate samples. Levels < 15 units/mL were considered the cut-off for normal sera. Serum ESR, CRP, levels of C3, C4, CH50, anti-DNAds titres, 25(OH)vitamin D, 24 hour protein excretion and SLEDAI were measured. A multivariate analysis was performed using SPSS 15.0.1. Adjustments were made for patients´age, disease duration and steroid daily dose (prednisolone equivalents). Results: 231 patients, 210 (90.91%) women, with mean (SD) age of 34.05 ± 9.63 years, were grouped according to BILAG renal score in categories A+B+C, category D and category E. All the patients with a history of nephritis (active or previous) had had a biopsy at the time of its diagnosis. They had mean (SD) disease duration of 33,83± 29,98 months, SLEDAI 19,5± 5,92, SLICC 1,39± 1,38, daily dose of prednisolone 10,87 ± 5.91mg.An association was found between active renal disease (BILAG score categories A+ B+ C) and higher anti-C1q titres (p<0.01), higher anti-dsDNA titres (p<0.01), SLEDAI, lower C3 levels (p<0.01). Conclusions: In a cohort of SLE patients, an association was found between anti-C1q titres, C3 levels and anti-dsDNA titres with active nephritis evaluated by BILAG renal scores. These data support the use of anti-C1q as a marker of nephritis presence and activity in SLE. Serum anti-C1q determination seems to be a valuable non-invasive marker for prediction of renal histopathology in lupus nephritis. MP331COMPARISON BETWEEN INTRAVENOUS CYCLOPHOSPHAMIDE (IVC) AND MYCHOPHENOLATE MOFETIL (MMF) AS INDUCTION AGENT IN LUPUS NEPHRITIS Irene Wong Irene Wong 1 Hospital Serdang, Kajang, Malaysia Fairol Huda Ibrahim Fairol Huda Ibrahim 1 Hospital Serdang, Kajang, Malaysia Bak Leong Goh Bak Leong Goh 1 Hospital Serdang, Kajang, Malaysia Thiam Seong Lim Thiam Seong Lim 1 Hospital Serdang, Kajang, Malaysia Mei Wah Chan Mei Wah Chan 1 Hospital Serdang, Kajang, Malaysia Abstract Introduction and Aims: Lupus nephritis (LN) is serious complication in systemic lupus erythematous (SLE), and proliferative LN predicts poorer outcome. In Malaysia, there is high prevalence of LN which accounts 74%. Recent publications have shown MMF with comparable treatment outcome compared to cyclophosphamide. Due to cost factors, IVC is still preferred as initial induction agent for proliferative LN in our region. Our aim was to evaluate efficacy and outcome between IVC and MMF and predictors of remission. Methods: This observational, cross sectional study which included 58 patients with biopsy proven LN class III, IV, V or mixed groups from year 2006 to 2012. Patients received either IVC of MMF for the first 6 months as induction therapy. Baseline characteristics and renal outcome, categorized into complete remission (CR), partial remission (PR) and never remission (NR) were compared at 6 months and 12 months of follow up. Results: The results below were described in mean, otherwise will be stated. There were 46 patients received IVC with dose 0.5g/m2 monthly, total cumulative dose 5.1g and 12 patients received MMF with maximum dose 2 g/day for 6 months. There was no significant difference between IVC and MMF in age (23.0,20.5) years, gender (female:84.8%,91.7%;male:15.2%,8.3%), 24-hour proteinuria or equivalent (3.3,3.5)g, eGFR at presentation (75.3,93.3) and albumin (24.0,26.5)g/dL. Time to remission for IVC and MMF groups were 6.0(2.6)months and 3.5(4.0)months, p=0.07. There was no significant difference in achieving CR,PR or NR between IVC and MMF at 6 and 12 months. Remission rate for both IVC and MMF were 73.9%,75.0% at 6 months, 82.6%,83.3% at 12 months, ESRD were 6.5%,8.3% and death were 4.3%,0.0% respectively. Remission as well as mortality and developing ESRD were not significant between these treatment groups. However, there was significant improvement of eGFR over 12 months follow up for IVC,p=0.04 as to MMF, p=0.30. Higher proteinuria at presentation and lower serum albumin were independent predictors of remission at 12 months. Proteinuria <2.5g/day predicts CR. Conclusions: In our cohort, IVC and MMF are equally effective and safe. Patients received IVC have better improvement in eGFR over 12 months period. Degree of proteinuria and albumin at presentation predict outcome. MP332MEMBRANOUS NEPHROPATHY: A LATE COMPLICATION OF CHRONIC GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Rikako Hiramtasu Rikako Hiramtasu 1 Toranomon Hospital, Tokyo, Japan Yoshifumi Ubara Yoshifumi Ubara 1 Toranomon Hospital, Tokyo, Japan Juinchi Hoshino Juinchi Hoshino 1 Toranomon Hospital, Tokyo, Japan Kenmei Takaichi Kenmei Takaichi 1 Toranomon Hospital, Tokyo, Japan Abstract Introduction and Aims: Renal involvement in patients with chronic graft-versus-host disease (cGVHD), presenting as nephritic syndrome, is rare following hematopoietic stem cell transplantation (HSCT). The most frequent form of cGVHD-associated glomerulonephritis is membranous nephropathy (MN); but data on its clinico-pathological features and long-term outcome are scarce. Methods: From 2000 to 2012, the clinical characteristics, pathological features, and long-term outcome were evaluated in 5 patients with MN after HSCT. Kidney biopsies were analyzed by light microscopy (LM), immunofluorescence (IF), electron microscopy (EM), and IgG subclasses in glomerular deposits were identified. Results: All patients had a history of cGVHD, with active cGVHD prior to MN diagnosis. Mean time between HSCT and diagnosis of MN was 21.8 months (range; 9-33). Serum creatinine was 1.0 mg/dL (0.8 to 1.3). Discontinuation of cGVHD prophylactic immunosuppressants prior to MN onset was a consistent feature, occurring at a median of 12.6 months (range; 2-25) before onset. Significant proteinuria (mean; 8.40 g/day, range; 5.93-13.0) was common. LM did not detect definite spike formation in capillary lumens. EM revealed subepithelial and intramembranous deposits, as well as mesangial deposits with extensive podocyte foot process effacement. Subepithelial deposits were segmental, small and electron-lucent. IF showed that IgG1 and IgG4 were the predominant IgG subclasses in glomerular deposits, which were negative for C3. All MN cases were initially treated with corticosteroids, resulting in complete remission (CR) at a median of 12.2 months (range; 5-24). Long-term follow up at a median of 92.4 months (range; 38-144) showed that relapse of MN paralleling the evolution of cGVHD occurred in 2 patients at 43 and 27 months after initial CR. One patient developed end-stage renal failure requiring hemodialysis. Conclusions: This series of 5 patients with post-HSCT MN is the largest study so far. Initial response to treatment was favorable, but careful observation for MN relapse parallel to cGVHD evolution, and long-term renal monitoring, are necessary. MP333COMPARING TWO CYCLOPHOSPHAMIDE REGIMES FOR TREATMENT OF ANCA ASSOCIATED VASCULITIS. Valeed Ghafoor Valeed Ghafoor 1 Royal Preston Hospital, Preston, United Kingdom Memuna Hussain Memuna Hussain 1 Royal Preston Hospital, Preston, United Kingdom Ajay Dhaygude Ajay Dhaygude 1 Royal Preston Hospital, Preston, United Kingdom Abstract Introduction and Aims: Cyclophosphamide (Cyp) has converted ANCA associated vasculitis (AAV) from a potential life-threatening disease to a remitting relapsing condition. Although Cyp is associated with significant dose related toxicity, poor control of disease inspite of Cyp treatment also remains a problem. EUVAS has recommended CYCLOPS protocol (Ten doses given over 26 weeks period) for treatment of AAV1. Extended course of Cyp (NIH regime- monthly Cyp for 6 months followed by quarterly doses for upto 30 months total) has been shown to reduce relapses in lupus nephritis2. Our centre has used both the regimes. In this study we have compared outcomes of AAV patients treated extended NIH regime and with CYCLOPS protocol. Methods: Retrospective study of 90 sequential AAV patients treated with2 Cyp regimes was performed. Data regarding demographics, rate of relapses, infective complications and, malignancies was collected. Results: In total 90 patients were identified. Fifty-seven patients received CYCLOPS protocol treatment and 33 received NIH regime. Results are presented in Table-1.More patients received Plasma exchange treatment in CYCLOPS group (33% compared to 18%) but renal survival was equal in both groups. Conclusions: Our findings suggest that like lupus nephritis, extended Cyp dosing regime is associated with reduced rate of relapses without increasing treatment related morbidity or mortality. Large RCT is required to confirm these findings.Limitations: Small sample size and retrospective study.Reference:1.Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.de Groot et al. Ann Intern Med. 2009 May 19;150(10):670-80.2.Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Boumpas et al. Lancet 1992. Sep26;340. Outcomes of two different Cyp regimes . NIH Regime . CYCLOPS regime . p value . Patients 33 57 Average age 58 60 Average F/U (pt*months) 56 (1848) 50 (2850) %ge PR-3 ANCA +ve 63 52 Relapses (relapse/pt*months) (0.003 relapse/pt*mth) (0.009 relapse/pt*mth) 0.01 Infections 6 (0.003 inf/pt*mth) 12 (0.004 inf/pt*mth) 0.44 Cumulative Cyp dose (mg) 8807 6951 Malignancies 6 10 0.68 . NIH Regime . CYCLOPS regime . p value . Patients 33 57 Average age 58 60 Average F/U (pt*months) 56 (1848) 50 (2850) %ge PR-3 ANCA +ve 63 52 Relapses (relapse/pt*months) (0.003 relapse/pt*mth) (0.009 relapse/pt*mth) 0.01 Infections 6 (0.003 inf/pt*mth) 12 (0.004 inf/pt*mth) 0.44 Cumulative Cyp dose (mg) 8807 6951 Malignancies 6 10 0.68 Outcomes of two different Cyp regimes . NIH Regime . CYCLOPS regime . p value . Patients 33 57 Average age 58 60 Average F/U (pt*months) 56 (1848) 50 (2850) %ge PR-3 ANCA +ve 63 52 Relapses (relapse/pt*months) (0.003 relapse/pt*mth) (0.009 relapse/pt*mth) 0.01 Infections 6 (0.003 inf/pt*mth) 12 (0.004 inf/pt*mth) 0.44 Cumulative Cyp dose (mg) 8807 6951 Malignancies 6 10 0.68 . NIH Regime . CYCLOPS regime . p value . Patients 33 57 Average age 58 60 Average F/U (pt*months) 56 (1848) 50 (2850) %ge PR-3 ANCA +ve 63 52 Relapses (relapse/pt*months) (0.003 relapse/pt*mth) (0.009 relapse/pt*mth) 0.01 Infections 6 (0.003 inf/pt*mth) 12 (0.004 inf/pt*mth) 0.44 Cumulative Cyp dose (mg) 8807 6951 Malignancies 6 10 0.68 MP334SURVIVAL OUTCOMES OF ELDERLY PATIENTS DIAGNOSED WITH ANCA ASSOCIATED VASCULITIS Steven Whatmough Steven Whatmough 1 Lancashire Teaching Hospitals, Preston, United Kingdom Sophie Fernandez Sophie Fernandez 1 Lancashire Teaching Hospitals, Preston, United Kingdom Niamh Sweeney Niamh Sweeney 1 Lancashire Teaching Hospitals, Preston, United Kingdom Memuna Hussain Memuna Hussain 1 Lancashire Teaching Hospitals, Preston, United Kingdom Ajay Dhaygude Ajay Dhaygude 1 Lancashire Teaching Hospitals, Preston, United Kingdom Abstract Introduction and Aims: ANCA associated (AAV) vasculitis is a multisystem disorder that usually presents in mid to late life. The average age at diagnosis is usually quoted as being between 60 and 70 years of age, however AAV can affect any age group. Information about outcomes of older patients presenting with AAV is limited1. In this study we compared outcomes of patients with AAV presenting before and after 75 years of age. Methods: All the patients diagnosed with AAV, between the years 1988 to 2010, within a tertiary centre, were included in this study. The cumulative dose of cyclophosphamide (CYP) was calculated to compare the standard of treatment received in both groups. Results: In total 284 patients were identified. The median age at diagnosis was 58 years (range 16 to 87 years). The regional incidence was 12.5 cases per million population. Forty-four patients were diagnosed at the age of, or after, 75 years.The median patient survival was 107 months for the younger group and 45 months for the older group (P=0.0047). Data regarding renal and patient survival is presented in table-1. Patient survival rates are illustrated in figure-1. Table 1. A summary of the patient/renal survival rates and the average CYP dose. . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average Cumulative CYP Dose (mg) . 3 Years . 5 Years . 3 Years . 5 Years . <75 Years 514.90 72% 63% 49% 43% 4329 >75 Years 548.62 54% 38% 36% 29% 2241 P Value 0.6361 0.0266 0.0034 0.1002 0.770 0.0126 . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average Cumulative CYP Dose (mg) . 3 Years . 5 Years . 3 Years . 5 Years . <75 Years 514.90 72% 63% 49% 43% 4329 >75 Years 548.62 54% 38% 36% 29% 2241 P Value 0.6361 0.0266 0.0034 0.1002 0.770 0.0126 Table 1. A summary of the patient/renal survival rates and the average CYP dose. . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average Cumulative CYP Dose (mg) . 3 Years . 5 Years . 3 Years . 5 Years . <75 Years 514.90 72% 63% 49% 43% 4329 >75 Years 548.62 54% 38% 36% 29% 2241 P Value 0.6361 0.0266 0.0034 0.1002 0.770 0.0126 . Presenting Creatinine (μmol/L) . Patient Survival . Renal Survival . Average Cumulative CYP Dose (mg) . 3 Years . 5 Years . 3 Years . 5 Years . <75 Years 514.90 72% 63% 49% 43% 4329 >75 Years 548.62 54% 38% 36% 29% 2241 P Value 0.6361 0.0266 0.0034 0.1002 0.770 0.0126 Open in new tabDownload slide Open in new tabDownload slide Conclusions: Our study suggests, 1. Patients who present with AAV at a younger age have improved patient survival rates. 2. Presenting creatinine was comparable between the two groups. 3. There was a trend towards improved renal survival in younger patients at five years. 4. There is a significant difference between the dose of CYP given to older patients diagnosed with AAV. This could possibly explain the difference in patient survival observed. Limitations: A relatively small number of patients in the older group and a retrospective study. Reference:1. Higgins, Goldsmith, Connolley, et al: Vasculitis and rapidly progressive glomerulonephritis in the elderly. Postgrad Med J. 1996 Jan;72(843):41-4. MP335INFECTION RELATED GLOMERULONEPHRITIS- AN EMERGING THREAT ! Manisha Sahay Manisha Sahay 1 Osmania Medical College and Teaching Hospital, Hyderabad, India Abstract Introduction and Aims: Infection related glomerulonephritis (IRGN) is a self-limited disease, especially in children, but long-term follow-up studies indicate persistent low-grade renal abnormalities in a significant proportion of patients. IRGN continues to be a serious public health concern in third world countries . This study compares IRGN in children and adults in an emerging country. Methods: A retrospective study of 209 patients (140 children and 69 adults) with IRGN identified during January 2005 - December 2011 was conducted. The diagnosis of IRGN was based on the clinical,serological and pathological features. The diagnosis of IRGN (post streptococcal) required positive testing of recent group A-beta hemolytic Streptococcal infection by either Anti-Streptolysin O antibody (ASO), or throat swab culture. Post non-Streptococcal GN was negative for streptococcal serology and included other bacteria or non-bacterial organisms. Renal biopsy was done in cases with renal failure or nephrotic proteinuria. The histological features by light microscopy (LM) and Immunoflourescence were semi-quantified. The patients were treated with antihypertensives, dialysis as and steroids were given for crescentic IRGN. The presentation, pathology and outcome were compared in children and adults and time to proteinuria less than 500 mg and time to normalization of serum creatinine were estimated. Statistical analysis was performed by using the SPSS statistical package. Results: Two hundred and nine cases of IRGN were identified. The median age was 21 + 11.9 years with 134 males and 75 females. The age ranged from 1 year to 95 years. There were 140 pediatric patients out of which 25 were less than 5 years of age. Proteinuria was detected in 97% children ( 60% had nephrotic range) and 84% adults. Microscopic hematuria was observed in 82% children and 60% adults. The low level of C3 was detected in 72.3% and 55%, respectively. Among children 128 ( 91.4 % )had post streptococcal GN while in adults 28( 40%) had non streptococcal GN. Overall 177 (84.6%)cases were post-streptococcal GN and 32 were non-Streptococcal GN. In 13 cases the causative pathogen could not be identified. One case was shunt nephritis, three cases were staphylococcal associated GN, two cases were tuberculosis associated GN, were 14 E coli related. Common sites of infection were throat 157( 75.1% ), skin 20(9.5% ), 14 Urinary tract (6.6%). Level of C3 was lower in the patients with post streptococcal GN (p < 0.05). 35 (25%) children and 30 (43.4%) adults needed dialysis. 26 (18.5%) children and 22 (31.8%) adults received steroids. The median times to resolution of proteinuria and normalization of serum creatinine were 2 months and 8 months in adults and 2 months and 4 months in children, respectively. 7 (5%) children progressed to CKD while among adults 12(17.3%) developed CKD. The mean follow up was for 3 years. 1 child and 3 adults succumbed during acute phase. Conclusions: IRGN continues to be prevalent in developing countries. Post streptococcal GN following throat infection is most common. Prognosis in children is better than adults with 5% children and 17% adults progressing to CKD. MP336PROLIFERATIVE GLOMERULONEPHRITIS WITH NON-IMMUNOGLOBULIN G MONOCLONAL IMMUNOGLOBULIN DEPOSITS Jun Soma Jun Soma 1 Iwate Prefectural Central Hospital, Morioka, Japan Izaya Nakaya Izaya Nakaya 1 Iwate Prefectural Central Hospital, Morioka, Japan Niriyo Sasaki Niriyo Sasaki 1 Iwate Prefectural Central Hospital, Morioka, Japan Kazuhiro Yoshikawa Kazuhiro Yoshikawa 1 Iwate Prefectural Central Hospital, Morioka, Japan Hiroshi Sato Hiroshi Sato 2 Tohoku University, Sendai, Japan Abstract Introduction and Aims: Proliferative glomerulonephritis (GN) with monoclonal immunoglobulin (Ig) G deposits is a rare but remarkable entity characterized by glomerular deposits of IgG, containing a single light-chain isotype and a single γ heavy-chain subclass. On electron microscopy, the deposits appear granular and electron-dense, mimicking those observed in immune-complex GN. Recently, cases of proliferative GN with monoclonal IgA or IgM deposits have been sporadically reported. In this study, we report a series of cases of proliferative GN with IgA or IgM deposits. Methods: We reviewed 1278 renal biopsies that were performed at the Iwate Prefectural Central Hospital in Morioka, Japan, from 2000 to 2013, and evaluated the clinicopathological and haematological features of patients with non-IgG monoclonal immunoglobulin deposits. When monoclonal IgM deposits were observed, cases with cryoglobulinemic GN were excluded. Results: We identified 5 patients with non-IgG monoclonal immunoglobulin deposits, including 3 with IgM-κ, one with IgM-λ and one with IgA1-λ. The mean age was 58 ± 12 years, and female/male ratio of the patients was 2/3. All patients showed proteinuria with hematuria; 4 patients showed nephrotic syndrome. Light microscopy revealed features of membranoproliferative GN, while electron microscopy revealed subendothelial and mesangial granular, electron-dense deposits mimicking those observed in immune-complex GN. An IF study showed that the distribution of heavy- and light-chains was identical. Serum protein electrophoresis identified monoclonal IgM-κ, IgM-λ and IgA-λ proteins in 2, one and one patient, respectively. The remaining patient had no monoclonal protein in the serum regardless of the presence of IgM-κ deposits in the renal glomerulus. Of the 4 patients with monoclonal protein in the serum, 2 with IgM-κ and one with IgA-λ showed normal free κ/λ ratios, while one patient with monoclonal IgM-κ in the serum showed a only slight increase free κ/λ ratio. The patient with serum monoclonal IgM-λ showed a marked decrease in free κ/λ ratio, with an underlying disease of lymphoproliferative disorder. Two patients with IgM-κ deposits were treated with prednisolone alone; their renal functions gradually deteriorated. Two patients with IgM-κ and IgM-λ deposits were treated with rituximab alone and rituximab in combination with cyclophsphamide and dexamethasone, respectively; these patients achieved complete remission. The patient with IgA1-λ deposits was treated with prednisolone alone and reached complete remission. Conclusions: These results show that: 1) there exists a group of renal disorders characterized by non-IgG monoclonal immunoglobulin deposits, 2) 4 out of 5 patients displayed monoclonal protein in their serum, but free κ/λ ratios were normal or remained slightly abnormal in 3 patients, 3) lymphoproliferative disorder or Waldemstrom’s macroglobulinemia was not always necessary for PGN development with monoclonal IgM deposits and 4) rituximab or rituximab plus alpha may be an effective treatment for PGN with monoclonal IgM deposits. MP337THE RELATIONSHIP BETWEEN ANTIGENS OF BLOOD GROUPS AND GLOMERULONEPHRITIS Vitaliy Kaminskyy Vitaliy Kaminskyy 1 Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine Abstract Introduction and Aims: Finding of biological markers of genetic predisposition to the formation of glomerulonephritis (GN) will promote prediction the probability of its development still at an early stage and provide the growth of preventive direction of medicine. The aim of this study was evaluating the risk of GN development by antigens of AB0 and rhesus (Rh) blood groups. Methods: The study included 434 patients with GN (242M, 192F, aged 37.56 ± 13.01y). To determine the distribution of phenotypes of AB0 and Rh blood groups in the population was surveyed 1428 healthy persons. For statistical analysis of the data was used the chi-square test (χ2) or Fisher's exact test and odds ratio (OR). Results: As among healthy persons, and among patients with GN the similar row of blood groups distribution was defined: A(II) > 0(I) > B(III) > AB(IV). However, statistically significant difference between patients with GN and healthy persons was detected, in particular - reducing in patients the frequency of phenotype 0(I) (χ2 = 4.21; OR 0.77, 95% confidence interval (CI) 0.61 to 0.98; p = 0.040) and increasing the frequency of phenotype AB(IV) (χ2 = 5.84; OR 1.59, 95% CI 1.11 to 2.28; p = 0.016). Also sexual features of distribution specified parameters was found. In male patients compared with healthy persons, decreasing the frequency of phenotype 0(I) (χ2 = 4.24; OR 0.68, 95% CI 0.48 to 0.97; p = 0.039) and increasing the frequency of phenotype A(II) (χ2 = 7.29; OR 1.57, 95% CI 1.14 to 2.15; p = 0.007) was observed. At the same time, in female patients - increasing the frequency of phenotype AB(IV) (χ2 = 9.88; OR 2.17, 95% CI 1.37 to 3.45; p = 0.002). During a comparative analysis of AB0 and Rh antigens combinations also were found the differences between the examined patients and healthy persons. Thus, in all patients the frequency of carriers antigens 0(I)Rh- was lower (χ2 = 16.17; OR 0.17, 95% CI 0.07 to 0.45; p = 0.000), and the frequency of carriers antigens A(II)Rh+ (χ2 = 4.08; OR 1.26, 95% CI 1.01 to 1.58; p = 0.043) and antigens AB(IV)Rh+ (χ2 = 5.15; OR 1.65, 95% CI 1.10 to 2.47; p = 0.023) was higher compared with healthy persons. Similar in patients of both sexes was reducing the frequency of phenotype 0(I)Rh-: in men (χ2 = 4.34; OR 0.25, 95% CI 0.07 to 0.94; p = 0.037) and in women (χ2 = 7.93; OR 0.19, 95% CI 0.05 to 0.68; p = 0.005). Simultaneously, the distinctive sign was increasing the frequency of phenotype A(II)Rh- in men (χ2 = 5.62; OR 2.34, 95% CI 1.20 to 4.57; p = 0.018), and in women - reducing of A(II)Rh- (χ2 = 6.30; OR 0.27, 95% CI 0.09 to 0.79; p = 0.012) and increasing of AB(IV)Rh+ (χ2 = 10.28; OR 2.39, 95% CI 1.43 to 3.98; p = 0.001). Conclusions: Our study showed the sexual dimorphism of genetic markers of hereditary susceptibility to GN: the greatest probability of GN development observed in men with phenotype A(II)Rh-, and in women - with phenotype AB(IV)Rh+. Rh-negative individuals of both sexes with group 0(I) and Rh-negative women with group A(II) may be resistant to the development of GN. MP338CD4+CD25+FOXP3+ REGULATORY, CD3+CD8+CD28- AND TH17 CELLS - THE IMPACT ON THE COURSE OF THE DISEASE IN PATIENTS WITH LUPUS NEPHRITIS Marcelina ŻAbińSka Marcelina ŻAbińSka 1 Wroclaw Medical University, Wroc&#322;aw, Poland Magdalena Krajewska Magdalena Krajewska 2 Wroclaw Medical University, Wroclaw, Poland Katarzyna KośCielska-Kasprzak Katarzyna KośCielska-Kasprzak 2 Wroclaw Medical University, Wroclaw, Poland Katarzyna Jakuszko Katarzyna Jakuszko 2 Wroclaw Medical University, Wroclaw, Poland Marian Klinger Marian Klinger 2 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction and Aims: The specific cause of SLE is unknown, although there is a range of immunological abnormalities in SLE, including disturbances in T-cell homeostasis.T regulatory cells (Tregs), a subset of CD4+, which express the transcription factor FoxP3, are involved in peripheral tolerance maintaining.T helper type 17 (Th17) cells are associated with the pathogenesis of many inflammatory and autoimmune diseases. These two subtypes of CD4+ T cells play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 had been demonstrated in several autoimmune diseases. Animal models of autoimmunity had also revealed that CD3+CD8+CD28- cells play a role in autoimmune diseases and can act as immunomodulator. However the results of studies concerning the CD3+CD8+CD28- cells are inconsistent since several studies describe CD3+CD8+CD28- as either immunosuppressive or cytotoxic.The aim of the study is to inquire whether the quantitative changes of T cells subpopulations are related to the clinical status of patients with lupus nephritis. Methods: 54 adult SLE patients (96,3% female, mean age 36,5±13,7) were enrolled in the study. Disease activity at the time of evaluation was scored according to SLEDAI and rSLEDAI indexes. Pts were divided into two groups based on SLEDAI score (inactive, ≤ 5: 15 pts; active, >5: 39 pts). The pts were also divided into three groups based on renal involvement by rSLEDAI scale (inactive, 0: 14 pts; medium active, 4: 15 pts; and active, ≥8: 25 pts). 19 sex-and-age matched healthy volunteers (89,5% female, mean age 38,3±14,1) were also included in the study. The absolute counts and percentage of CD4+CD25+FOXp3+, CD3+CD8+CD28- and CD4+IL17+ subpopulations were determined by flow cytometry. The experimental and clinical results were statistically analyzed using STATISTICA 10 software. Results: The SLE pts presented significantly lower absolute count (8,94 vs. 20,90 p<0,0001) and percentage (1,10 vs. 3,36 p<0,0001) of CD4+CD25+FOXp3+ cells compared to HC. The size of Th17 population was similar in both groups. The above resulted in decreased Treg/Th17 ratio in SLE pts vs. HC (0,80 vs. 1,93 p<0,0001). When pts were divided according to rSLEDAI there was a trend with Treg population decreasing with renal involvement. The significantly lowered absolute count and percentage of Tregs was observed in rSLEDAI active pts compared to rSLEDAI inactive pts (p=0,021, p=0,027, respectively).We also observed a statistically significant increase in absolute count (166,23 vs. 54,40 p=0,0002) and percentage (14,80 vs 6,10 p=0,0002) of CD3+CD8+CD28- cells in SLE pts compare to HC. Moreover, this subpopulation was larger in SLEDAI active vs SLEDAI inactive pts, both in absolute count (217,35 vs. 125,12 p=0,039) and percentage (21,00 vs. 7,30 p=0,022). Percentage of CD3+CD8+CD28- cells positively correlated with SLEDAI (rs= 0,28). Conclusions: The study demonstrated decreased absolute count of Treg cells in SLE pts compared to HC. Moreover, the frequency of Tregs showed an inverse correlation with renal disease activity.Although no differences were observed in the frequency of Th17 between two groups, the Treg/Th17 ratio was lower in SLE, suggesting that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response during disease exacerbation.Percentage of CD3+CD8+CD28- cells positively correlated with overall disease activity, confirming their cytotoxic phenotype. MP339THE RELATIONSHIP BETWEEN THE MANNAN-BINDING PROTEIN GENOTYPES AND CLINICAL MANIFESTATION OF LUPUS NEPHRITIS Zofia Niemir Zofia Niemir 1 University of Medical Sciences, Poznan, Poland Karol Wozniczka Karol Wozniczka 1 University of Medical Sciences, Poznan, Poland Anna Swierzko Anna Swierzko 2 Polish Academy of Sciences, Lodz, Poland Maciej Cedzynski Maciej Cedzynski 2 Polish Academy of Sciences, Lodz, Poland Magdalena Polcyn-Adamczak Magdalena Polcyn-Adamczak 1 University of Medical Sciences, Poznan, Poland Anna Sokolowska Anna Sokolowska 2 Polish Academy of Sciences, Lodz, Poland Agnieszka Szala Agnieszka Szala 2 Polish Academy of Sciences, Lodz, Poland Abstract Introduction and Aims: Mannan-binding lectin (MBL) has been suggested to have a dual mode of action in the development of systemic lupus erythematosus (SLE). Increased MBL leads to enhanced complement activation and tissue damage, while its deficiency results in aggravation of autoimmunity. Since serum MBL levels correlate with the presence of low (O/O and XA/O), intermediate (XA/XA and YA/) or high producing (YA/YA) MBL2 genotypes, we looked for the incidence of these genotypes in patients with lupus nephritis (LN) and tried to relate their occurrence with the clinical features of this disease. Methods: The study involved 99 patients with LN and 94 healthy controls (C). DNA was extracted from the whole blood and MBL2 genotyping was performed by the restriction fragment length polymorphism. Serum level of MBL was determined by an enzyme-linked immunosorbent assay. The activity of SLE was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K). Results: The YA/YA genotype was carried by 33.0% of patients with LN and 45.4% of C. The YA/XA heterozygosity was stated in 34.0% of patients with LN and in 30.3% of C. The YA/O or XA/XA genotypes were found in 23.4% of patients with LN and in 17.2% of C. The remaining 9.6% of patients with LN and 7.1% of C carried the O/O or XA/O genotypes. In LN and C, serum levels of MBL differed significantly between the high and low producing MBL2 genotypes (p<0.001), with no differences between the subgroups of these cohorts carrying the corresponding genotypes. However, when the activity of SLE was taken into account, it turned out that in patients with the YA/YA genotype, the median MBL level was significantly lower in inactive LN (inLN) compared to the active phase of the disease (aLN) (p<0.005). Of interest, in patients with aLN carrying the O/O+XA/O genotypes, a significantly higher level of anti-dsDNA antibodies was observed, compared to those with aLN presenting the YA/YA and YA/XA genotypes (p<0.01). In addition, a significant negative correlation between the levels of MBL and anti-dsDNA antibodies was noted in aLN with the YA/O+XA/XA and O/O+XA/O MBL2 genotypes (r=-0.649; p<0.01). Irrespective of MBL2 genotypes, a positive correlation between the level of MBL and glomerular filtration rate was obtained in inLN (r=0.33; p<0.05). Conclusions: The results of our study seem to point to MBL as to a biomarker protecting from the development of LN. Further studies are required to confirm this suggestion. MP340OUTCOMES IN PATIENTS WITH BIOPSY PROVEN RENAL VASCULITIS: A RETROSPECTIVE STUDY Aruna Arjunan Aruna Arjunan 1 Morriston Hospital, Swansea, Wales, United Kingdom Ashraf Mikhail Ashraf Mikhail 2 Morriston Hospital, Swansea , Wales, United Kingdom Rajesh Shrivastava Rajesh Shrivastava 2 Morriston Hospital, Swansea , Wales, United Kingdom Clare Parker Clare Parker 2 Morriston Hospital, Swansea , Wales, United Kingdom Sadanand Aithal Sadanand Aithal 3 Morriston Hospital, Swansea, United Kingdom Abstract Introduction and Aims: Vasculitides are a relatively uncommon group of conditions that present with a non-specific prodrome followed by life threatening organ damage including rapidly progressive glomerulonephritis and pulmonary haemorrhage. Early diagnosis and appropriate early immunosuppression play a key role in limiting organ damage and improving mortality. The aim of the study was to look at the management of biopsy proven renal vasculitis and the outcomes in these patients. Methods: A search of the histopathology records in Morriston Hospital between March 2006 and May 2012 revealed that 64 patients had a diagnosis of crescentic glomerulonephritis or focal segmental proliferative glomerulonephritis. Clinical data including demographics, biochemical data, data on clinical outcomes and treatment data on these patients were collected from electronic renal data base, discharge summaries, clinic letters and pharmacy records. Results: The median age at presentation was 68years (range 26-87yrs). 53.13% were male. All of them presented with acute kidney injury. 12.5% had pulmonary manifestations. Median serum creatinine(Cr) at presentation was 333μmol/L (mean 406 μmol/L, range 77 to 2020μmol/L). 70.32% had a Cr of < 500μmol/L at presentation. 78.12% were ANCA positive, 10.9% had antibodies to glomerular basement membrane (GBM), 6.25% were both ANCA and antiGBM positive and 7.81% were both negative. 46.25% had < 20% unaffected glomeruli and 53.44% had > 20% unaffected glomeruli. 46.5% had 50% crescents, 40.62% had 20-50% crescents and 7.81% had < 20% crescents. The treatment given included pulsed methyl prednisolone 500mgs IV x 3 followed by oral prednisolone 1mg/Kg body weight and monthly pulsed IV cyclophosphamide (750mg - 1gm) for 6 doses. 15.6% patients received oral Azathioprine (1.5mgs/Kg body weight) instead of cyclophosphamide. The rationale for this choice was not clear from the electronic files searched. Fewer patients with serum Cr < 500 μmol/L received cyclophosphamide. All patients were then maintained on oral Azathioprine at the above dose and oral prednisolone. 12.5% of patients received plasma exchange. Plasma exchange was given for 7-10 sessions or till antiGBM titres became negative. The 2 yr mortality was 18.75%. A total of 12 deaths occured in the 64 patients. The causes of death in 8 patients were not available. The causes of deaths in the remaining 4 were pulmonary haemorrhage, septicaemia and perforated colon. Conclusions: Stratification of serum Cr at 500 μmol/l and assessment of the percentage of normal glomeruli in a renal biopsy at presentation are useful tools in predicting renal outcome and mortality in patients with renal vasculitis. Development of ESRD and mortality were both lower in patients who presented with serum Cr of <500 μmol/L. Outcomes following stratification of serum Creatnine at 500μmol/l Outcomes . Cr >500μmol/l at presentation n=19 . Cr <500μmol/l at presentation n=45 . Initial Hemodialysis requirement 84.21% (16) 20% (9) ESRD or dialysis dependent renal failure 52.63% (10) 8.88% (4) Mortality from all causes in 1 year 15.7% (3) 13.33% (6) Mortality from all causes in 2years 31.5% (6) 15.5% (7) 1 year mortality in patients treated with cyclophosphamide 21.4% (3/14) 8.33% (2/24) 1 year mortality in patients not treated with cyclophosphamide 20.0% (1/5) 19.04%(4/21) ESRD or dialysis dependence in patients treated with cyclophosphamide 42.8% (6/14) 8.33% (2/24) ESRD or dialysis dependence in patients not treated with cyclophosphamide 80.0% (4/5) 9.54% (2/21) Outcomes . Cr >500μmol/l at presentation n=19 . Cr <500μmol/l at presentation n=45 . Initial Hemodialysis requirement 84.21% (16) 20% (9) ESRD or dialysis dependent renal failure 52.63% (10) 8.88% (4) Mortality from all causes in 1 year 15.7% (3) 13.33% (6) Mortality from all causes in 2years 31.5% (6) 15.5% (7) 1 year mortality in patients treated with cyclophosphamide 21.4% (3/14) 8.33% (2/24) 1 year mortality in patients not treated with cyclophosphamide 20.0% (1/5) 19.04%(4/21) ESRD or dialysis dependence in patients treated with cyclophosphamide 42.8% (6/14) 8.33% (2/24) ESRD or dialysis dependence in patients not treated with cyclophosphamide 80.0% (4/5) 9.54% (2/21) Outcomes following stratification of serum Creatnine at 500μmol/l Outcomes . Cr >500μmol/l at presentation n=19 . Cr <500μmol/l at presentation n=45 . Initial Hemodialysis requirement 84.21% (16) 20% (9) ESRD or dialysis dependent renal failure 52.63% (10) 8.88% (4) Mortality from all causes in 1 year 15.7% (3) 13.33% (6) Mortality from all causes in 2years 31.5% (6) 15.5% (7) 1 year mortality in patients treated with cyclophosphamide 21.4% (3/14) 8.33% (2/24) 1 year mortality in patients not treated with cyclophosphamide 20.0% (1/5) 19.04%(4/21) ESRD or dialysis dependence in patients treated with cyclophosphamide 42.8% (6/14) 8.33% (2/24) ESRD or dialysis dependence in patients not treated with cyclophosphamide 80.0% (4/5) 9.54% (2/21) Outcomes . Cr >500μmol/l at presentation n=19 . Cr <500μmol/l at presentation n=45 . Initial Hemodialysis requirement 84.21% (16) 20% (9) ESRD or dialysis dependent renal failure 52.63% (10) 8.88% (4) Mortality from all causes in 1 year 15.7% (3) 13.33% (6) Mortality from all causes in 2years 31.5% (6) 15.5% (7) 1 year mortality in patients treated with cyclophosphamide 21.4% (3/14) 8.33% (2/24) 1 year mortality in patients not treated with cyclophosphamide 20.0% (1/5) 19.04%(4/21) ESRD or dialysis dependence in patients treated with cyclophosphamide 42.8% (6/14) 8.33% (2/24) ESRD or dialysis dependence in patients not treated with cyclophosphamide 80.0% (4/5) 9.54% (2/21) Outcomes related to normal glomeruli count in 58 patients (data not available for 6 patients) Outcomes . >20% normal glomeruli n=31 . <20% normal glomeruli n=27 . 2 years mortality 19.35% (6) 14.8% (4) ESRD / dialysis dependence 6.45% (2) 29.6% (8) Outcomes . >20% normal glomeruli n=31 . <20% normal glomeruli n=27 . 2 years mortality 19.35% (6) 14.8% (4) ESRD / dialysis dependence 6.45% (2) 29.6% (8) Outcomes related to normal glomeruli count in 58 patients (data not available for 6 patients) Outcomes . >20% normal glomeruli n=31 . <20% normal glomeruli n=27 . 2 years mortality 19.35% (6) 14.8% (4) ESRD / dialysis dependence 6.45% (2) 29.6% (8) Outcomes . >20% normal glomeruli n=31 . <20% normal glomeruli n=27 . 2 years mortality 19.35% (6) 14.8% (4) ESRD / dialysis dependence 6.45% (2) 29.6% (8) MP341THE ROLE OF PENTRAXIN-3 IN DIFFERENT STAGES OF DIABETIC NEPHROPATHY Meltem Gursu Meltem Gursu 1 Haseki Training and Research Hospital, Istanbul, Turkey Muge Ozari Muge Ozari 1 Haseki Training and Research Hospital, Istanbul, Turkey Esma Yucetas Esma Yucetas 1 Haseki Training and Research Hospital, Istanbul, Turkey Abdullah Sumnu Abdullah Sumnu 1 Haseki Training and Research Hospital, Istanbul, Turkey Baris Doner Baris Doner 1 Haseki Training and Research Hospital, Istanbul, Turkey Egemen Cebeci Egemen Cebeci 1 Haseki Training and Research Hospital, Istanbul, Turkey Oktay Ozkan Oktay Ozkan 1 Haseki Training and Research Hospital, Istanbul, Turkey Mehmet Burak Aktuglu Mehmet Burak Aktuglu 1 Haseki Training and Research Hospital, Istanbul, Turkey Zeynep Karaali Zeynep Karaali 1 Haseki Training and Research Hospital, Istanbul, Turkey Macit Koldas Macit Koldas 1 Haseki Training and Research Hospital, Istanbul, Turkey Savas Ozturk Savas Ozturk 1 Haseki Training and Research Hospital, Istanbul, Turkey Abstract Introduction and Aims: It has been shown recently that immunological and inflammatory mechanisms have prominent roles in the development and progression of diabetic nephropathy (DNP). Early detection of inflammation and prevention of it when possible have great importance in these patients. Considering that CRP that is a widely used inflammatory marker is affected by many factors; it is obvious that there is need for more specific markers related with DNP independent from these factors. Although not widely used yet, pentraxin-3 seems to be a potential candidate. It is aimed in our study to measure levels of pentraxin-3 in different stages of DNP, observe changes with stages, and the relationship with other inflammatory markers. Methods: This is a cross-sectional study in which type 2 diabetic patients with DNP were included. Patients were divided into three groups. Group-1 included patients with eGFR>60ml/min and microalbuminuria; Group-2 included patients with eGFR>60ml/min and macroalbuminuria; and Group-3 included patients with eGFR<60ml/min and macroalbuminuria. Results: Besides routine laboratory data, pentraxin-3, hsCRP, IL-1 and TNF-α levels of patients were measured and recorded (Table-1 and 2). Pentraxin-3 levels in Group-2 and Group-3 were higher than that in Group-1. Correlation analysis of the whole groups revealed that there was correlation of only pentraxin-3 with proteinuria (r=0.266, p=0.016) and microalbuminuria (r=0.304, p=0.014). There was no significant correlation between other markers (IL-1, TNF-α and hsCRP). Moreover, levels of pentraxin-3, IL-1 and TNF-α increased with the stage of DNP; while there was no significant change in CRP levels. Conclusions: In patients with DNP, pentraxin-3 which belongs to long pentraxin group is a better marker of inflammation than CRP that is a short pentraxin. Table-1: Biochemical analysis results . Group-1 . Group-2 . Group-3 . p value . Glucose (mg/dl) 181±80 210±88 221±98 0.155 HbA1c (%) 8.33±1.68 8.98±1.93 8.94±1.78 0.230 Urea (mg/dl) 30.9±9.2 36.3±13.6 93.9±37.2 <0.001 Creatinin (mg/dl) 0.77±0.16 0.84±0.25 2.24±1.02 <0.001 Uric acid (mg/dl) 4.82±1.14 5.36±1.85 6.32±1.30 <0.001 Albumin (g/dl) 4.30±0.34 4.08±0.43 3.87±0.53 <0.001 ALT (U/L) 24.1±13.9 31.2±27.1 20.7±14.3 0.073 Calcium (mg/dl) 9.74±0.56 9.69±0.50 9.44±0.65 0.068 Phosphorus (mg/dl) 3.69±0.41 3.56±0.50 4.20±0.94 <0.001 PTH (pg/ml) 53±20 58±34 135±149 0.002 Total cholesterol (mg/dl) 221.12±40.21 223.81±66.35 224.51±71.56 0.969 Triglyceride (mg/dl) 203.27±76.11 257.11±249.61 221.88±98.30 0.356 LDL-cholesterol (mg/dl) 138.58±34.26 138.64±53.83 140.65±60.39 0.981 HDL-cholesterol (mg/dl) 43.35±10.64 42.88±10.80 41.40±9.61 0.710 Hgb (g/dl) 13.55±1.33 13.01±1.26 11.04±1.53 <0001 Leukocyte (x1000/mm3) 7.95±1.76 8.68±2.46 8.61±2.56 0.336 . Group-1 . Group-2 . Group-3 . p value . Glucose (mg/dl) 181±80 210±88 221±98 0.155 HbA1c (%) 8.33±1.68 8.98±1.93 8.94±1.78 0.230 Urea (mg/dl) 30.9±9.2 36.3±13.6 93.9±37.2 <0.001 Creatinin (mg/dl) 0.77±0.16 0.84±0.25 2.24±1.02 <0.001 Uric acid (mg/dl) 4.82±1.14 5.36±1.85 6.32±1.30 <0.001 Albumin (g/dl) 4.30±0.34 4.08±0.43 3.87±0.53 <0.001 ALT (U/L) 24.1±13.9 31.2±27.1 20.7±14.3 0.073 Calcium (mg/dl) 9.74±0.56 9.69±0.50 9.44±0.65 0.068 Phosphorus (mg/dl) 3.69±0.41 3.56±0.50 4.20±0.94 <0.001 PTH (pg/ml) 53±20 58±34 135±149 0.002 Total cholesterol (mg/dl) 221.12±40.21 223.81±66.35 224.51±71.56 0.969 Triglyceride (mg/dl) 203.27±76.11 257.11±249.61 221.88±98.30 0.356 LDL-cholesterol (mg/dl) 138.58±34.26 138.64±53.83 140.65±60.39 0.981 HDL-cholesterol (mg/dl) 43.35±10.64 42.88±10.80 41.40±9.61 0.710 Hgb (g/dl) 13.55±1.33 13.01±1.26 11.04±1.53 <0001 Leukocyte (x1000/mm3) 7.95±1.76 8.68±2.46 8.61±2.56 0.336 Table-1: Biochemical analysis results . Group-1 . Group-2 . Group-3 . p value . Glucose (mg/dl) 181±80 210±88 221±98 0.155 HbA1c (%) 8.33±1.68 8.98±1.93 8.94±1.78 0.230 Urea (mg/dl) 30.9±9.2 36.3±13.6 93.9±37.2 <0.001 Creatinin (mg/dl) 0.77±0.16 0.84±0.25 2.24±1.02 <0.001 Uric acid (mg/dl) 4.82±1.14 5.36±1.85 6.32±1.30 <0.001 Albumin (g/dl) 4.30±0.34 4.08±0.43 3.87±0.53 <0.001 ALT (U/L) 24.1±13.9 31.2±27.1 20.7±14.3 0.073 Calcium (mg/dl) 9.74±0.56 9.69±0.50 9.44±0.65 0.068 Phosphorus (mg/dl) 3.69±0.41 3.56±0.50 4.20±0.94 <0.001 PTH (pg/ml) 53±20 58±34 135±149 0.002 Total cholesterol (mg/dl) 221.12±40.21 223.81±66.35 224.51±71.56 0.969 Triglyceride (mg/dl) 203.27±76.11 257.11±249.61 221.88±98.30 0.356 LDL-cholesterol (mg/dl) 138.58±34.26 138.64±53.83 140.65±60.39 0.981 HDL-cholesterol (mg/dl) 43.35±10.64 42.88±10.80 41.40±9.61 0.710 Hgb (g/dl) 13.55±1.33 13.01±1.26 11.04±1.53 <0001 Leukocyte (x1000/mm3) 7.95±1.76 8.68±2.46 8.61±2.56 0.336 . Group-1 . Group-2 . Group-3 . p value . Glucose (mg/dl) 181±80 210±88 221±98 0.155 HbA1c (%) 8.33±1.68 8.98±1.93 8.94±1.78 0.230 Urea (mg/dl) 30.9±9.2 36.3±13.6 93.9±37.2 <0.001 Creatinin (mg/dl) 0.77±0.16 0.84±0.25 2.24±1.02 <0.001 Uric acid (mg/dl) 4.82±1.14 5.36±1.85 6.32±1.30 <0.001 Albumin (g/dl) 4.30±0.34 4.08±0.43 3.87±0.53 <0.001 ALT (U/L) 24.1±13.9 31.2±27.1 20.7±14.3 0.073 Calcium (mg/dl) 9.74±0.56 9.69±0.50 9.44±0.65 0.068 Phosphorus (mg/dl) 3.69±0.41 3.56±0.50 4.20±0.94 <0.001 PTH (pg/ml) 53±20 58±34 135±149 0.002 Total cholesterol (mg/dl) 221.12±40.21 223.81±66.35 224.51±71.56 0.969 Triglyceride (mg/dl) 203.27±76.11 257.11±249.61 221.88±98.30 0.356 LDL-cholesterol (mg/dl) 138.58±34.26 138.64±53.83 140.65±60.39 0.981 HDL-cholesterol (mg/dl) 43.35±10.64 42.88±10.80 41.40±9.61 0.710 Hgb (g/dl) 13.55±1.33 13.01±1.26 11.04±1.53 <0001 Leukocyte (x1000/mm3) 7.95±1.76 8.68±2.46 8.61±2.56 0.336 Table-2: Mean and standard deviations of inflammatory markers . Pentraxin-3 . IL-1 . CRP . TNF-α . Group-1 0.81±0.25 29.94±14.19 0.45±0.33 8.30±7.97 Group-2 0.94±0.26 48.66±14.97 0.97±1.21 15.42±14.01 Group-3 1.34±1.54 68.30±50.30 0.75±0.70 17.10±11.00 . Pentraxin-3 . IL-1 . CRP . TNF-α . Group-1 0.81±0.25 29.94±14.19 0.45±0.33 8.30±7.97 Group-2 0.94±0.26 48.66±14.97 0.97±1.21 15.42±14.01 Group-3 1.34±1.54 68.30±50.30 0.75±0.70 17.10±11.00 Table-2: Mean and standard deviations of inflammatory markers . Pentraxin-3 . IL-1 . CRP . TNF-α . Group-1 0.81±0.25 29.94±14.19 0.45±0.33 8.30±7.97 Group-2 0.94±0.26 48.66±14.97 0.97±1.21 15.42±14.01 Group-3 1.34±1.54 68.30±50.30 0.75±0.70 17.10±11.00 . Pentraxin-3 . IL-1 . CRP . TNF-α . Group-1 0.81±0.25 29.94±14.19 0.45±0.33 8.30±7.97 Group-2 0.94±0.26 48.66±14.97 0.97±1.21 15.42±14.01 Group-3 1.34±1.54 68.30±50.30 0.75±0.70 17.10±11.00 MP342ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY-NEGATIVE SMALL VESSEL VASCULITIS WITH RENAL INVOLVEMENT: A 24-YEAR RETROSPECTIVE STUDY Helena Marco Helena Marco 1 Germans Trias i Pujol, Badalona, Spain Montserrat Picazo Montserrat Picazo 2 Fundació Puigvert, Barcelona, Spain Iara Da Silva Iara Da Silva 2 Fundació Puigvert, Barcelona, Spain Ana Gonzalez Ana Gonzalez 1 Germans Trias i Pujol, Badalona, Spain Yolanda Arce Yolanda Arce 2 Fundació Puigvert, Barcelona, Spain Silvia Gracia Silvia Gracia 2 Fundació Puigvert, Barcelona, Spain Maria Corica Maria Corica 3 Hospital de La Santa Creu I Sant Pau, Barcelona, Spain Jm Llobet Jm Llobet 3 Hospital de La Santa Creu I Sant Pau, Barcelona, Spain Montserrat Diaz Montserrat Diaz 2 Fundació Puigvert, Barcelona, Spain Jose Ballarin Jose Ballarin 2 Fundació Puigvert, Barcelona, Spain Abstract Introduction and Aims: Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with antineutrophil cytoplasmic antibodies (ANCAs). However, ANCA´s are absent in 10 to 33% of cases.Prevalence, clinical manifestations, histopathology and outcomes of ANCA-negative small vessel vasculitis remain controversial. Methods: We performed a retrospective analysis of 117 cases of small vessel vasculitis with renal involvement assessed between 1985 and 2009 in two Spanish centers (Fundació Puigvert (N=104) and Germans Trias i Pujol (N=13)). Clinical and laboratory variables, presence and type of ANCA, kidney biopsy, immunosuppression therapy and renal/patient survival were evaluated.Proportions of patients were compared using Chi-Squared tests and serum creatinine by a t-student test. Results: 14/117 (12%) patients diagnosed with renal vasculitis were ANCA-negative. The mean age was 71.14±2.53 years in ANCA-negative and 63.56±1.42 years in ANCA-positive (p=0.07). Creatinine at diagnosis was 560.4±107.7 μmol/L in ANCA-negative and 430.3±23.26 μmol/L in ANCA-positive (p=0.08). There was not a statistically significant difference regarding clinical variables at diagnosis except for the presence of oliguria, 4/13 (31%) in the ANCA-negative and 6/87 (7%) in the ANCA-positive (p=0.025). 12/14 (86%) of the ANCA-negative received immunosuppressive therapy and 100% of the ANCA-positive (p=0.014). We observed similar number of infections in both groups (33 and 46% respectively p=0.54). The amount of patients that received dialysis at diagnosis was 8/13 (62%) of the ANCA-negative and 35/102 (34%) of the ANCA-positive (p=0.071). Mortality within 6 months of diagnosis was 6/12 (50%) of the ANCA-negative and 12/99 (12%) of the ANCA-positive (p=0.004). Conclusions: In our cohort of patients with ANCA-negative vasculitis, they had tendency to higher creatinine levels and higher tendency to require treatment with dialysis at diagnosis. A greater number of patients did not receive immunosuppressive therapy. The increase in mortality highlights the importance of early diagnosis and treatment of this disease despite the ANCA-negative to improve renal and patient survival. MP343HEPARIN-BINDING EPIDERMAL GROWTH FACTOR EXPRESSION IN ANCA-ASSOCIATED GLOMERULONEPHRITIS. Ulf Schönermarck Ulf Schönermarck 1 Ludwig-Maximilians-University, University Hospital Munich, München, Germany Holger Hägele Holger Hägele 1 Ludwig-Maximilians-University, University Hospital Munich, München, Germany Anne Baumgartner Anne Baumgartner 1 Ludwig-Maximilians-University, University Hospital Munich, München, Germany Michael Fischereder Michael Fischereder 1 Ludwig-Maximilians-University, University Hospital Munich, München, Germany Susanna Müller Susanna Müller 2 Ludwig-Maximilians-University, München, Germany Abstract Introduction and Aims: Recent experimental data implicate the involvement of heparin-binding epidermal growth factor (HB-EGF) in the development of antibody-mediated rapidly progressive glomerulonephritis. Increased HB-EGF expression has also been described in a limited number of patients with different forms of crescentic glomerulonephritis. In this retrospective study we investigated the expression of HB-EGF in kidney biopsies of patients with ANCA-associated vasculitis. Methods: Routine kidney biopsy specimens of patients with ANCA-associated vasculitis were classified according to the predominant glomerular lesion as recently proposed: focal, mixed, crescentic, and sclerotic. Immunohistochemical staining for HB-EGF was performed on formalin-fixed paraffin-embedded sections of renal biopsies using a commercially available mouse monoclonal antibody raised against mature HB-EGF of human origin. Results: Kidney biopsies from 35 patients with ANCA-associated vasculitis (MPO-ANCA+ n=19, PR3-ANCA+ n=16) were available for this retrospective analysis. Distribution of histologic lesions in this patient cohort was focal (n=4), crescentic (n=24), sclerotic (n=5) and mixed (n=2) according to the Leiden classification. HB-EGF expression was found in the majority of biopsy samples with diffuse (n=15) or focal staining (n=12), but was negative in 8 biopsy samples (crescentic, 5/24; focal, 2/4; mixed, 1/2; sclerotic, 0/5). Conclusions: HB-EGF expression can be frequently detected in kidney biopsies of patients with ANCA-associated glomerulonephritis. Further studies are warranted whether the HB-EGF pathway can be a target for therapeutic interventions in ANCA-associated glomerulonephritis. MP344LUPUS NEPHRITIS CLASS IV−G HAS A WORSE RENAL OUTCOME THAN CLASS IV−S: RETROSPECTIVE SINGLE CENTER COHORT Camila B. L. Oliveira Camila B. L. Oliveira 1 UFPE, Recofe, Brazil Alline S. A. Oliveira Alline S. A. Oliveira 2 UFPE, Recife, Brazil Clarissa J. B. Carvalho Clarissa J. B. Carvalho 2 UFPE, Recife, Brazil Carla T. B. C. Pessoa Carla T. B. C. Pessoa 2 UFPE, Recife, Brazil Luís H. B. C. Sette Luís H. B. C. Sette 2 UFPE, Recife, Brazil Gisele V. Fernandes Gisele V. Fernandes 2 UFPE, Recife, Brazil Maria Alina G. M. Cavalcante Maria Alina G. M. Cavalcante 2 UFPE, Recife, Brazil Lucila Maria Valente Lucila Maria Valente 2 UFPE, Recife, Brazil Abstract Introduction and Aims: The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) divided class IV into segmental (IV-S) and global (IV-G), based on evidence suggesting that diffuse segmental and global lupus nephritis may have different pathogenesis and outcomes. The aim of this study is to evaluate the possible pathological and clinical differences between these two subclasses. Methods: We conducted a retrospective single center cohort study of adult patients with biopsy proven class IV LN performed between 2004 and 2012, using ISN/RSP classification. Clinical characteristics, histopathological finds, serological data and long-term follow-up were analyzed. Results: Demographic data, clinical and prognostic characteristics are shown in Table 1 and Table 2. Table 1: Baseline characteristics of patients with lupus nephritis IV-S versus IV-G Baseline characteristics . IV-SN=49 . IV-GN=71 . p-value . Mean age, years 30.9±9.8 31.7±9.9 0.450 Gender (female/male), n 45/4 65/6 1.000 Race (non-white/white), % 61/39 60/40 1.000 Symptoms•Hematuria and/or NNP, %•Nephritic and nephrotic syndrome, %•RPGN, %•Nephrotic syndrome, % 33.331.227.010.5 10.025.755.78.5 0.0020.5360.0020.999 Hypertension (BP≥140x90mmHg), % 75.0 83.5 0.332 Time between lupus diagnosis and biopsy, years 4.0±3.0 3.0±4.3 0.123 Serum Cr, mg/dl 1.7±1.5 2.7±2.1 0.020 CrCl, ml/min/1,73m2 60.2±28.6 42.6±30.5 0.003 RRT, % 6.5 26.0 0.006 Serum albumin, mg/dl 2.7±0.8 2.5±0.7 0.318 Low C3, % 87.0 96.0 0.192 Low C4, % 72.0 84.4 0.350 Positive anti-ds-DNA, % 76.5 73.7 1.000 Proteinuria, g/24h 4.5±4.1 4.9±4.5 0.809 Proteinuria <3,5 g/24h, % 50.0 52.5 0.841 Hematuria, % 86.6 94.1 0.192 Crescents, % 51.0 73.0 0.019 Fibrinoid necrosis, % 6.3 4.2 0.684 Subendothelial hyaline deposits, % 18.8 25.3 0.504 Class V, % 32.6 19.7 0.134 IF/TA• Absent, %• Mild, %• Moderate, %• Severe, n % 4.168.825.02.0 5.650.738.05.6 1.0000.0590.1650.411 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 71.428.6 78.621.4 0.5740.574 Baseline characteristics . IV-SN=49 . IV-GN=71 . p-value . Mean age, years 30.9±9.8 31.7±9.9 0.450 Gender (female/male), n 45/4 65/6 1.000 Race (non-white/white), % 61/39 60/40 1.000 Symptoms•Hematuria and/or NNP, %•Nephritic and nephrotic syndrome, %•RPGN, %•Nephrotic syndrome, % 33.331.227.010.5 10.025.755.78.5 0.0020.5360.0020.999 Hypertension (BP≥140x90mmHg), % 75.0 83.5 0.332 Time between lupus diagnosis and biopsy, years 4.0±3.0 3.0±4.3 0.123 Serum Cr, mg/dl 1.7±1.5 2.7±2.1 0.020 CrCl, ml/min/1,73m2 60.2±28.6 42.6±30.5 0.003 RRT, % 6.5 26.0 0.006 Serum albumin, mg/dl 2.7±0.8 2.5±0.7 0.318 Low C3, % 87.0 96.0 0.192 Low C4, % 72.0 84.4 0.350 Positive anti-ds-DNA, % 76.5 73.7 1.000 Proteinuria, g/24h 4.5±4.1 4.9±4.5 0.809 Proteinuria <3,5 g/24h, % 50.0 52.5 0.841 Hematuria, % 86.6 94.1 0.192 Crescents, % 51.0 73.0 0.019 Fibrinoid necrosis, % 6.3 4.2 0.684 Subendothelial hyaline deposits, % 18.8 25.3 0.504 Class V, % 32.6 19.7 0.134 IF/TA• Absent, %• Mild, %• Moderate, %• Severe, n % 4.168.825.02.0 5.650.738.05.6 1.0000.0590.1650.411 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 71.428.6 78.621.4 0.5740.574 NNP: non-nephrotic proteinuria / RPGN: Rapidly progressive glomerulonephritis / Cr: Creatinine / Cl: Clearance / RRT: Renal replacement therapy / IF: Interstitial fibrosis / TA: Tubular atrophy Table 1: Baseline characteristics of patients with lupus nephritis IV-S versus IV-G Baseline characteristics . IV-SN=49 . IV-GN=71 . p-value . Mean age, years 30.9±9.8 31.7±9.9 0.450 Gender (female/male), n 45/4 65/6 1.000 Race (non-white/white), % 61/39 60/40 1.000 Symptoms•Hematuria and/or NNP, %•Nephritic and nephrotic syndrome, %•RPGN, %•Nephrotic syndrome, % 33.331.227.010.5 10.025.755.78.5 0.0020.5360.0020.999 Hypertension (BP≥140x90mmHg), % 75.0 83.5 0.332 Time between lupus diagnosis and biopsy, years 4.0±3.0 3.0±4.3 0.123 Serum Cr, mg/dl 1.7±1.5 2.7±2.1 0.020 CrCl, ml/min/1,73m2 60.2±28.6 42.6±30.5 0.003 RRT, % 6.5 26.0 0.006 Serum albumin, mg/dl 2.7±0.8 2.5±0.7 0.318 Low C3, % 87.0 96.0 0.192 Low C4, % 72.0 84.4 0.350 Positive anti-ds-DNA, % 76.5 73.7 1.000 Proteinuria, g/24h 4.5±4.1 4.9±4.5 0.809 Proteinuria <3,5 g/24h, % 50.0 52.5 0.841 Hematuria, % 86.6 94.1 0.192 Crescents, % 51.0 73.0 0.019 Fibrinoid necrosis, % 6.3 4.2 0.684 Subendothelial hyaline deposits, % 18.8 25.3 0.504 Class V, % 32.6 19.7 0.134 IF/TA• Absent, %• Mild, %• Moderate, %• Severe, n % 4.168.825.02.0 5.650.738.05.6 1.0000.0590.1650.411 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 71.428.6 78.621.4 0.5740.574 Baseline characteristics . IV-SN=49 . IV-GN=71 . p-value . Mean age, years 30.9±9.8 31.7±9.9 0.450 Gender (female/male), n 45/4 65/6 1.000 Race (non-white/white), % 61/39 60/40 1.000 Symptoms•Hematuria and/or NNP, %•Nephritic and nephrotic syndrome, %•RPGN, %•Nephrotic syndrome, % 33.331.227.010.5 10.025.755.78.5 0.0020.5360.0020.999 Hypertension (BP≥140x90mmHg), % 75.0 83.5 0.332 Time between lupus diagnosis and biopsy, years 4.0±3.0 3.0±4.3 0.123 Serum Cr, mg/dl 1.7±1.5 2.7±2.1 0.020 CrCl, ml/min/1,73m2 60.2±28.6 42.6±30.5 0.003 RRT, % 6.5 26.0 0.006 Serum albumin, mg/dl 2.7±0.8 2.5±0.7 0.318 Low C3, % 87.0 96.0 0.192 Low C4, % 72.0 84.4 0.350 Positive anti-ds-DNA, % 76.5 73.7 1.000 Proteinuria, g/24h 4.5±4.1 4.9±4.5 0.809 Proteinuria <3,5 g/24h, % 50.0 52.5 0.841 Hematuria, % 86.6 94.1 0.192 Crescents, % 51.0 73.0 0.019 Fibrinoid necrosis, % 6.3 4.2 0.684 Subendothelial hyaline deposits, % 18.8 25.3 0.504 Class V, % 32.6 19.7 0.134 IF/TA• Absent, %• Mild, %• Moderate, %• Severe, n % 4.168.825.02.0 5.650.738.05.6 1.0000.0590.1650.411 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 71.428.6 78.621.4 0.5740.574 NNP: non-nephrotic proteinuria / RPGN: Rapidly progressive glomerulonephritis / Cr: Creatinine / Cl: Clearance / RRT: Renal replacement therapy / IF: Interstitial fibrosis / TA: Tubular atrophy Table 2: Renal outcomes of patients with lupus nephritis IV-S versus IV-G Outcomes . IV-SN=28 . IV-GN=44 . p-value . Follow-up, months 26.8±22.7 27.5±25.3 Serum Cr, mg/dl 1.0±0.5 2.3±1.2 0.011 CrCl, ml/min/1,73m2 71.9±21.9 53.0±32.2 0.030 CR, % 46.4 28.5 0.205 PR, % 42.8 50.0 0.809 Time to CR or PR, months 9.8±5.8 7.5±5.0 0.096 Doubling Cr, % 17.8 47.7 0.012 CrCl < 30 ml/min/1,73m2, % 7.1 34.0 0.010 RRT, % 0.0 20.5 0.023 Outcomes . IV-SN=28 . IV-GN=44 . p-value . Follow-up, months 26.8±22.7 27.5±25.3 Serum Cr, mg/dl 1.0±0.5 2.3±1.2 0.011 CrCl, ml/min/1,73m2 71.9±21.9 53.0±32.2 0.030 CR, % 46.4 28.5 0.205 PR, % 42.8 50.0 0.809 Time to CR or PR, months 9.8±5.8 7.5±5.0 0.096 Doubling Cr, % 17.8 47.7 0.012 CrCl < 30 ml/min/1,73m2, % 7.1 34.0 0.010 RRT, % 0.0 20.5 0.023 Cr: Creatinine / Cl: Clearance / CR: Complete remission / PR: Partial Remission/ RRT: Renal replacement therapy Table 2: Renal outcomes of patients with lupus nephritis IV-S versus IV-G Outcomes . IV-SN=28 . IV-GN=44 . p-value . Follow-up, months 26.8±22.7 27.5±25.3 Serum Cr, mg/dl 1.0±0.5 2.3±1.2 0.011 CrCl, ml/min/1,73m2 71.9±21.9 53.0±32.2 0.030 CR, % 46.4 28.5 0.205 PR, % 42.8 50.0 0.809 Time to CR or PR, months 9.8±5.8 7.5±5.0 0.096 Doubling Cr, % 17.8 47.7 0.012 CrCl < 30 ml/min/1,73m2, % 7.1 34.0 0.010 RRT, % 0.0 20.5 0.023 Outcomes . IV-SN=28 . IV-GN=44 . p-value . Follow-up, months 26.8±22.7 27.5±25.3 Serum Cr, mg/dl 1.0±0.5 2.3±1.2 0.011 CrCl, ml/min/1,73m2 71.9±21.9 53.0±32.2 0.030 CR, % 46.4 28.5 0.205 PR, % 42.8 50.0 0.809 Time to CR or PR, months 9.8±5.8 7.5±5.0 0.096 Doubling Cr, % 17.8 47.7 0.012 CrCl < 30 ml/min/1,73m2, % 7.1 34.0 0.010 RRT, % 0.0 20.5 0.023 Cr: Creatinine / Cl: Clearance / CR: Complete remission / PR: Partial Remission/ RRT: Renal replacement therapy Conclusions: We found clinical and pathological differences between LN class IV-S and IV-G groups. Patients with biopsy proven LN class IV-G had more rapidly progressive glomerulonephritis clinically, with a worse baseline creatinine clearance, and a higher risk of renal disease progression and renal replacement therapy. MP345IS MYCOPHENOLATE MOFETIL COMBINED WITH LOW- DOSE PREDNISONE AN EFFECTIVE THERAPEUTIC OPTION FOR CHINESE PATIENTS WITH LEE CLASS III, IV, V IGA NEPHROPATHY? Qijun Wan Qijun Wan 1 Shenzhen Second People’s Hospital, Guangdong Province, P.R.China, Shenzhen, China Haofei Hu Haofei Hu 1 Shenzhen Second People’s Hospital, Guangdong Province, P.R.China, Shenzhen, China Yongcheng He Yongcheng He 1 Shenzhen Second People’s Hospital, Guangdong Province, P.R.China, Shenzhen, China Tong Li Tong Li 1 Shenzhen Second People’s Hospital, Guangdong Province, P.R.China, Shenzhen, China Abstract Introduction and Aims: A few prospective randomized controlled trials have proved that mycophenolate mofetil (MMF) could induce lasting remission of proteinuria and preserve the glomerular filtration rate (GFR) in Chinese patients who had less advanced immunoglobulin A nephropathy (IgAN) [1,2]. But its tolerance and effectiveness in Chinese patients with Lee class III,IV,VIgAN remains unclear. The primary objective of this study was to evaluate the safety and efficacy of MMF combined with low-dose prednisone as a therapeutic regimen on urine proteinuria excretion and renal preservation in a Chinese population of patients with Lee class III, IV, V IgAN. Methods: This was a single-center study. Of 45 Lee class III,IV,V IgAN patients that were followed up in our renal centre in recently years (from 2006 to 2012) were included. The treatment regime was MMF (1~1.5g /day for six months, then 0.5~1.0g /day for the next six months, and then 0.25~0.5g /day for the last six months) plus low-dose prednisone (0.5 mg/kg.day for two months, then slowly tapered by 5 mg every two weeks until discontinuation). All patients received angiotensin inhibition medication. Total follow-up was 1 year. The change of urine total protein excretion and serum creatinine (Scr) was tested at the point of baseline and 12th months of the treatment in all patients. Estimated GFR (eGFR) was calculated according to the modified MDRD equation for Chinese. Results: At the point of follow-up one year, the urine total protein excretion was statistically lower than that of baseline in each group, respectively (Lee class III: 0.22 ± 0.14 versus 1.63 ± 1.13, P = 0.000, Lee class IV: 0.41 ± 0.32 versus 2.01 ± 1.41, P = 0.000, Lee class V: 0.29 ± 0.06 versus 2.82 ± 1.32, P = 0.000). The remission rate of proteinuria in the 45 patients was 77.4 %, while in Lee class III patients was statistically higher than that in Lee class IV(90.9 % versus 76.2 %, P = 0.037) and Lee class V patients(90.9 % versus 50 %, P=0.046), respectively. At the 12 th month of follow-up, renal function remained stable compared with the baseline level in each group as evidenced by serum and eGFR, respectively. (serum creatinine: Lee class III: 82.33 ± 26.06 versus 90.41 ± 38.86, P = 0.196, Lee class IV: 128.69 ± 48.71 versus 144.26 ± 50.92, P = 0.353, Lee class V: 193.51 ± 69.08 versus 255.92 ± 98.66, P = 0.007; eGFR: Lee class III: 104.11 ± 50.75 versus 95.63 ± 41.68, P=0.396, Lee class IV: 63.65 ± 23.88 versus 54.64 ± 23.36, P = 0.136, Lee class V: 53.38 ± 21.33 versus 28.92 ± 14.62, P = 0.032 ). There were four (8.9 %) severe pneumonia patients in the present study. All the four severe pneumonia developed in Lee class V group, while there was no severe patient in the Lee class IIIand IVgroup patients in the present study. The difference was statistically. Conclusions: MMF combined with low-dose prednisone can reduce proteinuria and preserve renal function in Chinese patients with Lee class III, IV, V IgA nephropathy. The worse the renal function, the lower the proteinuria remission rate. Chronically impaired renal function may be a risk factor for severe pneumonia. This finding needs to be further evaluated. MP346LATE ONSET LUPUS NEPHRITIS Narjisse Aazair Narjisse Aazair 1 IBN ROCHD Universital Hospital, Casablanca, Morocco Zineb Houmaid Zineb Houmaid 2 IBN ROCHD University Hospital, Casablanca, Morocco Asmaa Rhair Asmaa Rhair 2 IBN ROCHD University Hospital, Casablanca, Morocco Nisrine Bennani Nisrine Bennani 2 IBN ROCHD University Hospital, Casablanca, Morocco Abstract Introduction and Aims: Renal involvement is a common site of systemic lupus erythematosus responsible for high morbidity and mortality in young subjects. It usually appears during the first to the fifth year of disease progression. The late-onset lupus nephritis is a rare and poorly studied entity. The aim of our work is to study the epidemiological, clinical, biological and histological characteristics of lupus nephritis occurring beyond 50 years, compared with younger subjects. Methods: Retrospective monocentric study conducted on all lupus nephritis biopsied in our formation over a period of 7 years (2006- 2013). 24 patients aged over 50 years were collected (G1) compared to a sample of 190 younger patients (G2). All patients met the ACR criteria. Results: The average age was 58 years in G1 vs 29 years in the G2; the sex ratio was 75 % of women in G1 vs 90% in G2. Renal involvement was inaugural in 58.3 % of cases in G1 vs 61% in G2. Hypertension was seen in 60 % of cases in G1 vs 21.46 % in G2. Proteinuria was present in all cases in G1 with an average of 3.5 g / d against 93% in G2. Renal failure was seen in 60% of cases with a mean serum creatinine of 30 mg / l in G1 against 21% in G2. Hematuria and leucocyturia were present in respectively 62 % and 54% in G1 vs 32% and 38% in G2. In histology the proliferative form was predominant in G1, primarily represented by the class IV (56.5 %) with a mean index of activity at 5 and chronicity at 4, followed by the class V (17.4%). In G2 classes III and IV were found in 34.5% of cases each. Treatment in the 2 groups was based on corticosteroids and / or immunosuppressants according to histological form. Remission was seen in 41% of cases in G1 vs 74% in G2, worsening was seen in 66% of cases in G1 against 24% in G2 with progression to ESRD in 33 % in G1 and 14.5 % in G2. Death was comparable in the 2 groups with 8.3% in G1 vs 9% in the G2. Conclusions: Although late-onset lupus appears to have a benign course, it seems that the renal localization, even rare, is an element of poor prognosis because of the more frequent progression to ESRD and the therapeutic challenges in patients with multiple comorbidities. MP347AUTOLOGOUS HEMATOPOIETIC STEM CELLS TRANSPLANTATION FOR SEVERE REFRACTORY SLE WITH LUPUS NEPHRITIS: REMOTE OUTCOME WITH ALLOGENEIC KIDNEY TRANPLANTATION Aleksandr Demin Aleksandr Demin 1 Novosibirsk State Medical University, Novosibirsk, Russian Federation O. Petrova O. Petrova 1 Novosibirsk State Medical University, Novosibirsk, Russian Federation O. Kotova O. Kotova 1 Novosibirsk State Medical University, Novosibirsk, Russian Federation L. Demina L. Demina 1 Novosibirsk State Medical University, Novosibirsk, Russian Federation Abstract Introduction and Aims: Systemic lupus erythematosus (SLE) is a severe autoimmune disease that affects multiple organ systems. Lupus nephritis is a common part of the disease associated with pure prognosis. Patients with lupus nephritis who experience persisted disease activity despite conventional immunosuppression are at high risk of early death. Re-setting of the immune system and self-tolerance by high-dose immunosuppressive therapy with autologous stem cell transplantation (ASCT) is a new approach in the treatment of refractory SLE. Remote outcomes of this method and effectiveness relapse treatment are still unclear and were the aims of this study. Methods: We report a 33-years woman with refractory severe lupus nephritis. At the disease start SLE criteria was nephritis with proteinuria, hematuria, malar rash, arthritis, antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) positivity. Renal biopsy established lupus nephritis class IV-G (A) (ISN/RPS, 2003). SLEDAI score was 23. Standard therapy with prednisolone, 1 mg/kg, daily and cyclophosphamide, 1000 mg, once a month during 1 year was ineffective, SLEDAI score remains 22 so patient was underwent high dose immunosuppressive therapy protocol with ASCT and included in European Group for Blood and Marrow Transplantation/ EULAR registry on 53 pts who received ASCT for SLE between 1996 and 2002. Ethical approval was obtained for this study from Cambridge University Hospital ethics committee. Results: The ASCT induced complete clinical and serological remission (SLEDAI score was 0) for 3 years. Than relapse with nephritic syndrome and anti-dsDNA positivity occurred and caused renal failure, creatinine clearance decreased to 21. Despite therapy, including prednisolone, 45 mg daily, and mycophenolate mofetil, 2000 mg daily, disease activity persisted, creatinine clearance remained decreasing and 3 years later became 15 ml/min. During 1 year patient was on regular hemodialysis, than renal transplantation performed. Now, follow up is 9 years after ASCT and 2 years after kidney transplantation. Patient received a standard post-transplant immunosuppression with prednisolone, 5 mg daily, tacrolimus, 2.5 mg daily and azathioprine, 100 mg daily and her conditions remains stable, she has functioning renal allograft, SLEDAI score is 2 (anti-dsDNA positivity in low titer). Conclusions: We present the first case of immunoablation and successful double transplantation of autologous hematopoietic stem cells and allogeneic kidney in severe refractory to conventional immunosuppression lupus nephritis. MP348INTENSIFIED B LYMPHOCYTE DEPLETION (IBLD) WITHOUT IMMUNOSUPPRESSIVE MAINTENANCE TREATMENT AS A RESCUE THERAPY IN REFRACTORY LUPUS NEPHRITIS (LN): A 4-YEAR OBSERVATION Dario Roccatello Dario Roccatello 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy 2 Nephrology and Dialysis Division, Torino, Italy Savino Sciascia Savino Sciascia 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Daniela Rossi Daniela Rossi 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Carla Naretto Carla Naretto 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Simone Baldovino Simone Baldovino 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Mirella Alpa Mirella Alpa 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Ilaria Salussola Ilaria Salussola 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Vittorio Modena Vittorio Modena 1 Department of Rare, Immunological, Hematological and Immunohematological Diseases, Torino, Italy Abstract Introduction and Aims: B-lymphocytes (BL) play a critical role in Systemic Lupus Erythematosus (SLE). BL depletion therapy still remains an attractive option, despite the disappointing results of RCTs. We aim to report our 4-year experience after intensified b lymphocyte depletion (IBLD). Methods: Twelve SLE patients [2 males, mean age 43.8 yrs (29-54)] with polyarthralgia and multiorgan involvement including class IV or III/V (ISN/RPS) glomerulonephritis (9 cases), skin lesions (9 cases, with necrotizing ulcers in 3), polyneuropathy (7 cases, with CNS involvement in 2), lymphoadenopathy (6) e polysierositis (5) were treated with an IBLD protocol due to intolerance to conventional immunosuppressive therapy (6 cases) or as front line therapy (6 cases). Protocol: Rituximab 375 mg/sm on days 1, 8, 15, and 22, and 2 more doses after one and two months, associated with 2 i.v. administrations of 10 mg/kg of cyclophosphamide, and 3 infusions of methylprednisolone (15 mg/kg) followed by oral prednisone (0.8 mg/die, rapidly tapered to 5 mg/day in 10 weeks). No further immunosuppressive maintenance therapy was administered. Results: IBLD resulted in complete depletion of CD20+ BL for 12-18 months. Patients were followed-up for 48.9 (25-93) months. Significant decreases (p<0.05) were found in the ESR levels (baseline mean value: 54.2 mm; 3 months: 33 mm; end of follow-up: 14.9 mm), anti-dsDNA antibodies (baseline: 192 U; 3 months: 112 U ; end of follow-up: 17 U) and proteinuria (baseline: 4.9 g/24 hours; 3 months: 0.97 g/24 hours; end of follow-up: 0.22 g/24 hours). Conversely, C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of follow-up (20 mg/dl).Three patients relapsed after 36, 41 and 72 months, respectively. Following re-treatment, they again showed complete remission over 13-48 months of observation. Conclusions: These data confirm the advisability to reconsider the regimens of BL depletion in the treatment of the most severe forms of SLE despite the disappointing results of RCTs. A promising role of Rituximab in protocols of “intensified induction therapy” in selected patients for whom avoiding immunosuppressive maintenance therapy is particularly appealing can be envisaged. MP349IMMUNOSUPPRESSIVE TREATMENT FOR GLOMERULONEPHRITIS AND SYSTEMIC DISEASES IN ELDERLY PATIENTS (ONE CENTER EXPERIENCE) Elena V Zakharova Elena V Zakharova 1 City Clinical Hospital N.A. S.P. Botkin, Moscow, Russian Federation Olga V Vinogradova Olga V Vinogradova 1 City Clinical Hospital N.A. S.P. Botkin, Moscow, Russian Federation Ekaterina S Stolyarevich Ekaterina S Stolyarevich 2 Nephrology Center, Moscow, Russian Federation Abstract Introduction and Aims: Immunosuppressive therapy in older people is considered to be poor tolerated and associated with severe adverse events due to comorbidities, mainly cardiovascular diseases, diabetes and obesity. However, conditions as rapidly progressive glomerulonephritis and severe nephrotic syndrome may demand immunosuppression. We aimed to evaluate outcomes of immunosuppressive treatments in our cohort of elderly patients. Methods: Using electronic database we searched all cases aged over 60, treated with immunosuppressant’s for biopsy proven glomerular diseases of native kidneys during 1994-2012. Treatment regimens included corticosteroids alone or in combination with cyclophosphamide, chlorambucil, mycophenolates, azathioprine and cyclosporine; cyclosporine alone and rituximab for primary and secondary glomerulonephritis. For “primary” AL-amyloidosis we used melphalan with prednisolone or dexamethasone, or bortezomib. Results: Study group included 393 cases (15% out of 2701 admissions for immunosuppression), 209 females and 184 males, median age 69 [61; 81] years. Diagnosis and treatment regimens are shown in table 1. Among primary glomerulonephritis membranous nephropathy (43%) and focal segmental glomerulosclerosis (35%) prevailed. In ANCA-associated vasculitidies dominated microscopic polyangiitis - 50% of admissions. Treatment outcomes are shown in table 2. Conclusions: In vast majority of admissions indication for immunosuppression was nephrotic syndrome or rapidly progressive glomerulonephritis due to membranous nephropathy, focal segmental glomerulosclerosis, “primary” AL-amlyloidosis and microscopic polyangiitis, which is characteristic for older population. Therapeutic regimens shifted over last decade towards selective immunosuppressant’s and biological agents, but as we evaluated treatment for almost 20 years, most widely used therapeutic regimens for primary and secondary glomerulonephritis were prednisolone combined with cyclophosphamide or cyclosporine; and for “primary" amyloidosis - melphalan with prednisolone. However, partial remissions were seen in 62%, and complete remissions - in 27% of cases, adverse events rate was as low as 9%, and proportion of deaths - only 4%, suggesting that immunosuppressive treatment may be effective and well tolerated even in elderly patients with severe glomerular diseases. Main diagnosis and treatment regimens . Primary glomerulonephritis . Lupus nephritis . ANCA- assosiated vasculitis . Cryoglobulinemic vasculitis . Henoch- Shonlein purpura . Goodpasture's disease . "Primary' AL-amyloidosis . Prednisolone alone 6 (16%) 10 14 38 2 0 0 0 Prednisolone plus cyclophosphamide 84 (21%) 16 6 56 2 3 1 0 Prednisolone plus chlorambucil 6 (2%) 6 0 0 0 0 0 0 Prednisolone plus azathioprine 25 (6%) 0 7 18 0 0 0 0 Prednisolone plus mycophenolate 23 (6%) 14 1 8 0 0 0 0 Prednisolone plus cyclosporine 77 (20%) 77 0 0 0 0 0 0 Cyclosporine alone 49 (12%0 49 0 0 0 0 0 0 Rituximab 7 (2%) 3 0 4 0 0 0 0 Melphalan plus prednisolone 32 (8%) 0 0 0 0 0 0 32 Melphalan plus dexamethasone 16(4%) 0 0 0 0 0 0 16 Bortezomib 10 (3%) 0 0 0 0 0 0 10 Total 175 28 124 4 3 1 58 Total % 45 7 32 1 1 <1 15 . Primary glomerulonephritis . Lupus nephritis . ANCA- assosiated vasculitis . Cryoglobulinemic vasculitis . Henoch- Shonlein purpura . Goodpasture's disease . "Primary' AL-amyloidosis . Prednisolone alone 6 (16%) 10 14 38 2 0 0 0 Prednisolone plus cyclophosphamide 84 (21%) 16 6 56 2 3 1 0 Prednisolone plus chlorambucil 6 (2%) 6 0 0 0 0 0 0 Prednisolone plus azathioprine 25 (6%) 0 7 18 0 0 0 0 Prednisolone plus mycophenolate 23 (6%) 14 1 8 0 0 0 0 Prednisolone plus cyclosporine 77 (20%) 77 0 0 0 0 0 0 Cyclosporine alone 49 (12%0 49 0 0 0 0 0 0 Rituximab 7 (2%) 3 0 4 0 0 0 0 Melphalan plus prednisolone 32 (8%) 0 0 0 0 0 0 32 Melphalan plus dexamethasone 16(4%) 0 0 0 0 0 0 16 Bortezomib 10 (3%) 0 0 0 0 0 0 10 Total 175 28 124 4 3 1 58 Total % 45 7 32 1 1 <1 15 Main diagnosis and treatment regimens . Primary glomerulonephritis . Lupus nephritis . ANCA- assosiated vasculitis . Cryoglobulinemic vasculitis . Henoch- Shonlein purpura . Goodpasture's disease . "Primary' AL-amyloidosis . Prednisolone alone 6 (16%) 10 14 38 2 0 0 0 Prednisolone plus cyclophosphamide 84 (21%) 16 6 56 2 3 1 0 Prednisolone plus chlorambucil 6 (2%) 6 0 0 0 0 0 0 Prednisolone plus azathioprine 25 (6%) 0 7 18 0 0 0 0 Prednisolone plus mycophenolate 23 (6%) 14 1 8 0 0 0 0 Prednisolone plus cyclosporine 77 (20%) 77 0 0 0 0 0 0 Cyclosporine alone 49 (12%0 49 0 0 0 0 0 0 Rituximab 7 (2%) 3 0 4 0 0 0 0 Melphalan plus prednisolone 32 (8%) 0 0 0 0 0 0 32 Melphalan plus dexamethasone 16(4%) 0 0 0 0 0 0 16 Bortezomib 10 (3%) 0 0 0 0 0 0 10 Total 175 28 124 4 3 1 58 Total % 45 7 32 1 1 <1 15 . Primary glomerulonephritis . Lupus nephritis . ANCA- assosiated vasculitis . Cryoglobulinemic vasculitis . Henoch- Shonlein purpura . Goodpasture's disease . "Primary' AL-amyloidosis . Prednisolone alone 6 (16%) 10 14 38 2 0 0 0 Prednisolone plus cyclophosphamide 84 (21%) 16 6 56 2 3 1 0 Prednisolone plus chlorambucil 6 (2%) 6 0 0 0 0 0 0 Prednisolone plus azathioprine 25 (6%) 0 7 18 0 0 0 0 Prednisolone plus mycophenolate 23 (6%) 14 1 8 0 0 0 0 Prednisolone plus cyclosporine 77 (20%) 77 0 0 0 0 0 0 Cyclosporine alone 49 (12%0 49 0 0 0 0 0 0 Rituximab 7 (2%) 3 0 4 0 0 0 0 Melphalan plus prednisolone 32 (8%) 0 0 0 0 0 0 32 Melphalan plus dexamethasone 16(4%) 0 0 0 0 0 0 16 Bortezomib 10 (3%) 0 0 0 0 0 0 10 Total 175 28 124 4 3 1 58 Total % 45 7 32 1 1 <1 15 Treatment outcomes . Complete remissions . Partial remissions . Total remissions . No effect . Adverse events . Death . Primary glomerulonephritis175 89 68 157 18 8 2 Lupus nephritis28 5 21 26 2 5 2 ANCA-associated vasculitis124 13 100 113 11 17 7 Cryoglobulinemic vasculitis4 0 3 3 1 2 1 Henoch-Shonlein purpura3 0 3 3 0 1 0 Goodpasture's disease1 0 0 0 1 0 1 "Primary" AL-amyloidosis58 0 50 50 8 4 3 Total 107 245 352 41 37 16 Total % 27 62 89 11 9 4 . Complete remissions . Partial remissions . Total remissions . No effect . Adverse events . Death . Primary glomerulonephritis175 89 68 157 18 8 2 Lupus nephritis28 5 21 26 2 5 2 ANCA-associated vasculitis124 13 100 113 11 17 7 Cryoglobulinemic vasculitis4 0 3 3 1 2 1 Henoch-Shonlein purpura3 0 3 3 0 1 0 Goodpasture's disease1 0 0 0 1 0 1 "Primary" AL-amyloidosis58 0 50 50 8 4 3 Total 107 245 352 41 37 16 Total % 27 62 89 11 9 4 Treatment outcomes . Complete remissions . Partial remissions . Total remissions . No effect . Adverse events . Death . Primary glomerulonephritis175 89 68 157 18 8 2 Lupus nephritis28 5 21 26 2 5 2 ANCA-associated vasculitis124 13 100 113 11 17 7 Cryoglobulinemic vasculitis4 0 3 3 1 2 1 Henoch-Shonlein purpura3 0 3 3 0 1 0 Goodpasture's disease1 0 0 0 1 0 1 "Primary" AL-amyloidosis58 0 50 50 8 4 3 Total 107 245 352 41 37 16 Total % 27 62 89 11 9 4 . Complete remissions . Partial remissions . Total remissions . No effect . Adverse events . Death . Primary glomerulonephritis175 89 68 157 18 8 2 Lupus nephritis28 5 21 26 2 5 2 ANCA-associated vasculitis124 13 100 113 11 17 7 Cryoglobulinemic vasculitis4 0 3 3 1 2 1 Henoch-Shonlein purpura3 0 3 3 0 1 0 Goodpasture's disease1 0 0 0 1 0 1 "Primary" AL-amyloidosis58 0 50 50 8 4 3 Total 107 245 352 41 37 16 Total % 27 62 89 11 9 4 MP350EFFECT OF LONG-TERM TACROLIMUS TREATMENT IN PATIENTS WITH LUPUS NEPHRITIS Desmond Y.H. Yap Desmond Y.H. Yap 1 The University of Hong Kong, Hong Kong, Hong Kong Tak Mao Chan Tak Mao Chan 1 The University of Hong Kong, Hong Kong, Hong Kong Abstract Introduction and Aims: Tacrolimus (TAC) is an effective immunosuppressant and reduces proteinuria in chronic glomerulopathies. Long-term data on TAC in the treatment of lupus nephritis (LN) is lacking. Methods: This is a retrospective analysis of LN patients who had received TAC treatment for >6 months during 2003-2013. Results: 29 patients were included (follow-up 46.9±37.9 months). TAC was given as add-on therapy to prednisolone plus azathioprine or mycophenolate in 17 patients. These patients had Class III/IV+/-V LN and persistent proteinuria >2g/D after induction immunosuppression (Group I). TAC and prednisolone was given as initial treatment in 10 patients with Class V LN and nephrotic syndrome (Group II). TAC was used as steroid-sparing agent in 2 patients with lupus podocytopathy (Group III). 12- and 24-month complete/partial response rates were 66.7%/80.0% for Group I and 60.0/90.0%% for Group II. Prednisolone maintenance dose was reduced in Group III after the addition of TAC. For the whole group, the mean proteinuria decreased from 3.6±2.6 g/d to 1.0±1.1 g/d (p<0.05). 4 patients developed endstage renal failure, with 3-, 5-, and 8-year renal survival rates of 93%, 83% and 83% respectively. In the remaining patients, serum creatinine and estimated glomerular filtration rate was stable after 36 months (p=0.072 and 0.083). 4 renal flares occurred, all associated with low (≤3 ng/L) TAC trough blood levels. C3 level increased over time (p=0.02), while anti-dsDNA, blood pressure, glycemic and lipid profiles did not change significantly. New onset or deterioration of hypertension or diabetes mellitus occurred in 6 (20.1%) and 1 (3.4%) patients. 6 (20.1%) patients had infections that required hospitalization. One patient with pre-existing chronic renal failure developed TAC nephrotoxicity. Two deaths occurred, due to pneumonia and breast cancer respectively. Conclusions: This preliminary experience suggests that TAC can be an effective treatment option in some LN patients, and warrant further investigations on treatment optimization and tolerability. MP351COMPARATIVE STUDY BETWEEN PRIMARY AND SECONDARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS - A SINGLE CENTRE EXPERIENCE Vijay Thanaraj Vijay Thanaraj 1 Royal Preston Hopsital, Preston, United Kingdom Ajay Dhaygude Ajay Dhaygude 1 Royal Preston Hopsital, Preston, United Kingdom Arvind Ponnusamy Arvind Ponnusamy 1 Royal Preston Hopsital, Preston, United Kingdom Sreenath Pillai Sreenath Pillai 2 Nottingham University Hospital NHS Trust, Nottingham, United Kingdom Abstract Introduction and Aims: Focal Segmental Glomerulosclerosis (FSGS) is a common histological diagnosis encompassing variety of clinical presentations. Main verities include primary and secondary to loss of nephron mass. Immunohistochemistry shows IgM and C3 deposition in primary FSGS which are typically absent in secondary FSGS. Full blown nephrotic presentation (proteinuria, oedema, hyperlipidaemia , and hypoalbuminaemia ) is rare in secondary FSGS and main stay of treatment is rennin angiotensin aldosterone system (RAAS) blockade while Nephrotic syndrome is common in primary FSGS and relentless progression to end stage renal disease (ESRD) is common though immunosuppression has been used with success for treatment. Although both primary and secondary FSGS are common, published data lacks comparative studies. In this study we compared degree of proteinuria, serum albumin, response to RAAS blockade, incidence of thrombo-embolism and incidence of ESRD Methods: This is a retrospective review of 51 patients with biopsy proven FSGS diagnosed between 1997-2008. Data regarding demographics, laboratory parameters, treatment details, incidence of thrombo-embolism and patient outcomes were collected Results: Average age at presentation was 50.33 ± 10.26 years and 54% were male. The follow up period was 2678.30 ± 1627.6 days.RAAS blockade therapy was initiated in 90% of secondary FSGS and in 76.19% of primary FSGS. Differences in the clinical features, laboratory parameters and outcomes are presented in Table-1. Conclusions: In this study, 1] Classical nephrotic presentation was more common in Primary FSGS 2] Response to RAAS blockade was superior in Secondary FSGS 3] Thrombo-embolism was absent in Secondary FSGS. MP352RETROSPECTIVE STUDY ON RECURRENT GLOMERULONEPHRITIS IN THE TRANSPLANTED KIDNEY: OUR CASE STUDY Lucia Argentiero Lucia Argentiero 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Antonio Schena Antonio Schena 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Michele Rossini Michele Rossini 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Carlo Manno Carlo Manno 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Giuseppe Castellano Giuseppe Castellano 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Marida Martino Marida Martino 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Adele Mitrotti Adele Mitrotti 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Marica Giliberti Marica Giliberti 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Chiara Digiorgio Chiara Digiorgio 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Anna Maria Di Palma Anna Maria Di Palma 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Michele Battaglia Michele Battaglia 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Pasquale Ditonno Pasquale Ditonno 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Giuseppe Grandaliano Giuseppe Grandaliano 2 Department of Medical and Surgical Sciences, Univ. of Foggia, Foggia, Italy Loreto Gesualdo Loreto Gesualdo 1 Department of Emergency and Organ Transplantation, Univ. of Bari, Bari, Italy Abstract Introduction and Aims: Despite advances in prevention of acute rejection and improved short- and long-term kidney graft survival, recurrent glomerulonephritis remains problematic and poorly characterized. Few data are available on the impact of glomerulonephritis on the transplanted kidney. The risk factors are largely unknown or imprecise. Moreover, the occurrence of glomerunephritis is very difficult to predict.This study analyzed the incidence of various histological types of recurrent glomerulonephritis (RGN) in our center in the last twenty years. It also sought to identify the potential risk factors for recurrence. Methods: We studied 1319 renal transplant patients who had been followed at our center from 1992 to 2012. 451 patients, who presented worsening of renal function (as suggested by a 30% increase in serum creatinine), onset of urinary abnormalities, nephrotic syndrome, underwent percutaneous needle biopsy of the transplanted kidney. Demographic, clinical and histological features of the RGN were compared with a control group ( n. 58 renal transplant patients who did not develop glomerulonephritis). Potential risk factors for disease recurrence were analysed. Results: The histological diagnoses were different: 156/451 (34.58%) chronic allograft nephropathy (CAN), 89/451 (19.73%) glomerulonephritis, 84/451 (18.62%) acute rejection, 78/451 (17.29%) acute tubular necrosis, 26/451 (5.76%) were normal, 11/451 (2.43%) thrombotic microangiopathy, 7/451 (1.55%) cortical necrosis.For 39/89 (43.82%) patients of the glomerulonephritis group, primary kidney disease was unknown. The histological diagnoses in this group were: 17/39 (43.58%) IgA nephropathy, 7/39 (17.94%) FSGS, 5/39 (12.82%) necrotizing extracapillary GN, 6/39 (15.38%) MPGN.22/89 (24.71%) of patients showed a de novo glomerulonephritis. The histological diagnoses were: 8/22 (36.4%) IgA nephropathy, 5/22 (22.7%) FSGS, 2/22 (9.1%) necrotizing extracapillary GN, 3/22 (13.63%) MGN, 1/22 (4.54%) amyloidosis.The remaining 28/89 (31.46%) showed RGN with 22/28 (78.57%) IgA nephropathy, 3/28 (10.71%) FSGS, 3/28 (10.71%) MPGN. Interestingly, in our cohort we found a significant correlation of RGN with young age ( 36.6 ± SD in recurrent GN vs 42.4 ± SD in non recurrent GN (p= 0.02)) and the presence of CAN (8/28 in RGN vs 4/58 in control group (p= 0.006)). We did not find significative differences between RGN on control group for age at transplant, sex, living/deceased donors, duration of dialysis, type of dialysis if HD or PD, delayed graft function recovery, the type of immunosuppressive therapy, re- transplantation, acute rejection, chronic allograft nephropathy. Conclusions: Post-transplant glomerulonephritis can be de novo or recurrence of the original glomerular disease. In our study, we found IgA nephropathy as the most common form of RGN. For many renal transplant patients the histological diagnosis of their underlying renal disease is often not available. It is possible that the young age of the transplant patient and the development of a chronic allograft dysfunction during transplantation expose the patient to the development of a RGN. MP353RENAL OUTCOMES IN CRESCENTIC LUPUS NEPHRITIS: RETROSPECTIVE SINGLE CENTER COHORT Camila B. L. Oliveira Camila B. L. Oliveira 1 UFPE, Recife, Brazil Clarissa J. B. Carvalho Clarissa J. B. Carvalho 1 UFPE, Recife, Brazil Alline S. A. Oliveira Alline S. A. Oliveira 1 UFPE, Recife, Brazil Carla T. B. C. Pessoa Carla T. B. C. Pessoa 1 UFPE, Recife, Brazil Luís H. B. C. Sette Luís H. B. C. Sette 1 UFPE, Recife, Brazil Gisele V. Fernandes Gisele V. Fernandes 1 UFPE, Recife, Brazil Maria Alina G. M. Cavalcante Maria Alina G. M. Cavalcante 1 UFPE, Recife, Brazil Lucila Maria Valente Lucila Maria Valente 1 UFPE, Recife, Brazil Abstract Introduction and Aims: Crescentic nephritis can be a manifestation of diffuse global proliferative lupus nephritis (class IV-G) and it usually presents with rapid deterioration of renal functions. The purpose of this study is to evaluate the differences of clinical characteristics, pathological features and renal outcomes between patients with crescentic or not crescentic class IV-G. Methods: We conducted a retrospective single center cohort study of adult patients with biopsy proven lupus nephritis (LN) class IV-G, using International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, performed between 2004 and 2012. Clinical characteristics, pathological finds, serological data and long-term follow-up were analyzed. Results: Demographic data, clinical and prognostic characteristics are shown in Table 1 and Table 2. Table 1: Baseline characteristics of patients with LN class IV-G crescentic versus not crescentic . CrescenticIV-GN=25 . Not CrescenticIV-GN=46 . p-value . Mean age, years 33.4±8.8 30.8±10.4 0.220 Gender (female/male), n 24/01 41/5 0.414 Race (non-white/white), % 63/37 58/42 0.773 Symptoms• Hematuria and/or NNP, %• Nephritic and nephrotic syndrome, %• RPGN, %• Nephrotic syndrome, % 0.016.787.50.0 15.631.140.013.3 0.0420.255 <0.0010.085 Hypertension (BP≥140x90mmHg), % 87.0 81.8 0.735 Time between lupus diagnosis and biopsy, years 4.0±5.6 2.0±3.0 0.43 Serum Cr, mg/dl 4.0±2.6 2.1±1.6 0.007 CrCl, ml/min/1,73m2 30.0±27.2 49.2±30.0 0.009 RRT, % 45.8 15.6 0.009 Serum albumin, mg/dl 3.0±0.6 2.6±0.7 0.812 Low C3, % 94.1 97.1 1.000 Low C4, % 85.7 83.9 1.000 Positive anti-ds-DNA, % 100.0 64.3 0.256 Proteinuria, g/24h 4.0±2.3 5.3±5.0 0.694 Proteinuria <3,5 g/24h, % 52.9 52.4 1.000 Hematuria, % 87.0 97.8 0.108 Number of glomeruli, n 9.0±4.0 12.5±7.9 0.182 Sub-class A, %Sub-class A/C, %Sub-class C, % 4.096.00.0 10.987.02.1 0.4140.4081.000 Activity index, nChronicity index, n 10±24±2 8±24±2 0.1810.305 Endocapillary hipercellularity, %Fibrinoid necrosis, %Subendothelial hyaline deposits, % 100.00.020.0 93.56.528.3 0.3050.3050.119 Class V, % 28.0 15.2 0.223 IF / TA• Absent, %• Mild, %• Moderate, %• Severe, n % 0.048.044.08.0 8.752.234.84.3 0.2890.8060.6090.609 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 87.512.5 73.026.9 0.4420.442 . CrescenticIV-GN=25 . Not CrescenticIV-GN=46 . p-value . Mean age, years 33.4±8.8 30.8±10.4 0.220 Gender (female/male), n 24/01 41/5 0.414 Race (non-white/white), % 63/37 58/42 0.773 Symptoms• Hematuria and/or NNP, %• Nephritic and nephrotic syndrome, %• RPGN, %• Nephrotic syndrome, % 0.016.787.50.0 15.631.140.013.3 0.0420.255 <0.0010.085 Hypertension (BP≥140x90mmHg), % 87.0 81.8 0.735 Time between lupus diagnosis and biopsy, years 4.0±5.6 2.0±3.0 0.43 Serum Cr, mg/dl 4.0±2.6 2.1±1.6 0.007 CrCl, ml/min/1,73m2 30.0±27.2 49.2±30.0 0.009 RRT, % 45.8 15.6 0.009 Serum albumin, mg/dl 3.0±0.6 2.6±0.7 0.812 Low C3, % 94.1 97.1 1.000 Low C4, % 85.7 83.9 1.000 Positive anti-ds-DNA, % 100.0 64.3 0.256 Proteinuria, g/24h 4.0±2.3 5.3±5.0 0.694 Proteinuria <3,5 g/24h, % 52.9 52.4 1.000 Hematuria, % 87.0 97.8 0.108 Number of glomeruli, n 9.0±4.0 12.5±7.9 0.182 Sub-class A, %Sub-class A/C, %Sub-class C, % 4.096.00.0 10.987.02.1 0.4140.4081.000 Activity index, nChronicity index, n 10±24±2 8±24±2 0.1810.305 Endocapillary hipercellularity, %Fibrinoid necrosis, %Subendothelial hyaline deposits, % 100.00.020.0 93.56.528.3 0.3050.3050.119 Class V, % 28.0 15.2 0.223 IF / TA• Absent, %• Mild, %• Moderate, %• Severe, n % 0.048.044.08.0 8.752.234.84.3 0.2890.8060.6090.609 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 87.512.5 73.026.9 0.4420.442 NNP: non-nephrotic proteinuria / RPGN: Rapidly progressive glomerulonephritis / Cr: Creatinine / Cl: Clearance / RRT: renal replacement therapy / A: Acute / C: Chronic / IF: Interstitial fibrosis / TA: Tubular atrophy Table 1: Baseline characteristics of patients with LN class IV-G crescentic versus not crescentic . CrescenticIV-GN=25 . Not CrescenticIV-GN=46 . p-value . Mean age, years 33.4±8.8 30.8±10.4 0.220 Gender (female/male), n 24/01 41/5 0.414 Race (non-white/white), % 63/37 58/42 0.773 Symptoms• Hematuria and/or NNP, %• Nephritic and nephrotic syndrome, %• RPGN, %• Nephrotic syndrome, % 0.016.787.50.0 15.631.140.013.3 0.0420.255 <0.0010.085 Hypertension (BP≥140x90mmHg), % 87.0 81.8 0.735 Time between lupus diagnosis and biopsy, years 4.0±5.6 2.0±3.0 0.43 Serum Cr, mg/dl 4.0±2.6 2.1±1.6 0.007 CrCl, ml/min/1,73m2 30.0±27.2 49.2±30.0 0.009 RRT, % 45.8 15.6 0.009 Serum albumin, mg/dl 3.0±0.6 2.6±0.7 0.812 Low C3, % 94.1 97.1 1.000 Low C4, % 85.7 83.9 1.000 Positive anti-ds-DNA, % 100.0 64.3 0.256 Proteinuria, g/24h 4.0±2.3 5.3±5.0 0.694 Proteinuria <3,5 g/24h, % 52.9 52.4 1.000 Hematuria, % 87.0 97.8 0.108 Number of glomeruli, n 9.0±4.0 12.5±7.9 0.182 Sub-class A, %Sub-class A/C, %Sub-class C, % 4.096.00.0 10.987.02.1 0.4140.4081.000 Activity index, nChronicity index, n 10±24±2 8±24±2 0.1810.305 Endocapillary hipercellularity, %Fibrinoid necrosis, %Subendothelial hyaline deposits, % 100.00.020.0 93.56.528.3 0.3050.3050.119 Class V, % 28.0 15.2 0.223 IF / TA• Absent, %• Mild, %• Moderate, %• Severe, n % 0.048.044.08.0 8.752.234.84.3 0.2890.8060.6090.609 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 87.512.5 73.026.9 0.4420.442 . CrescenticIV-GN=25 . Not CrescenticIV-GN=46 . p-value . Mean age, years 33.4±8.8 30.8±10.4 0.220 Gender (female/male), n 24/01 41/5 0.414 Race (non-white/white), % 63/37 58/42 0.773 Symptoms• Hematuria and/or NNP, %• Nephritic and nephrotic syndrome, %• RPGN, %• Nephrotic syndrome, % 0.016.787.50.0 15.631.140.013.3 0.0420.255 <0.0010.085 Hypertension (BP≥140x90mmHg), % 87.0 81.8 0.735 Time between lupus diagnosis and biopsy, years 4.0±5.6 2.0±3.0 0.43 Serum Cr, mg/dl 4.0±2.6 2.1±1.6 0.007 CrCl, ml/min/1,73m2 30.0±27.2 49.2±30.0 0.009 RRT, % 45.8 15.6 0.009 Serum albumin, mg/dl 3.0±0.6 2.6±0.7 0.812 Low C3, % 94.1 97.1 1.000 Low C4, % 85.7 83.9 1.000 Positive anti-ds-DNA, % 100.0 64.3 0.256 Proteinuria, g/24h 4.0±2.3 5.3±5.0 0.694 Proteinuria <3,5 g/24h, % 52.9 52.4 1.000 Hematuria, % 87.0 97.8 0.108 Number of glomeruli, n 9.0±4.0 12.5±7.9 0.182 Sub-class A, %Sub-class A/C, %Sub-class C, % 4.096.00.0 10.987.02.1 0.4140.4081.000 Activity index, nChronicity index, n 10±24±2 8±24±2 0.1810.305 Endocapillary hipercellularity, %Fibrinoid necrosis, %Subendothelial hyaline deposits, % 100.00.020.0 93.56.528.3 0.3050.3050.119 Class V, % 28.0 15.2 0.223 IF / TA• Absent, %• Mild, %• Moderate, %• Severe, n % 0.048.044.08.0 8.752.234.84.3 0.2890.8060.6090.609 Treatment• Cyclophosphamide, %• Mycophenolate mofetil, % 87.512.5 73.026.9 0.4420.442 NNP: non-nephrotic proteinuria / RPGN: Rapidly progressive glomerulonephritis / Cr: Creatinine / Cl: Clearance / RRT: renal replacement therapy / A: Acute / C: Chronic / IF: Interstitial fibrosis / TA: Tubular atrophy Table 2: Renal outcomes of patients with LN class IV-G crescentic versus not crescentic . Crescentic IV-GN=18 . Not Crescentic IV-GN=26 . p-value . Follow-up, months 22.0±25.7 31.3±24.4 0.059 Serum Cr, mg/dl 2.7±2.0 2.0±2.4 0.083 CrCl, ml/min/1,73m2 40.0±28.3 62.0±31.7 0.046 CR, % 6.3 42.3 0.030 PR, % 68.8 38.5 0.010 Doubling Cr, % 72.2 30.8 0.013 CrCl < 30 ml/min/1,73m2, % 50.0 23.1 0.105 RRT, % 33.3 15.4 0.272 . Crescentic IV-GN=18 . Not Crescentic IV-GN=26 . p-value . Follow-up, months 22.0±25.7 31.3±24.4 0.059 Serum Cr, mg/dl 2.7±2.0 2.0±2.4 0.083 CrCl, ml/min/1,73m2 40.0±28.3 62.0±31.7 0.046 CR, % 6.3 42.3 0.030 PR, % 68.8 38.5 0.010 Doubling Cr, % 72.2 30.8 0.013 CrCl < 30 ml/min/1,73m2, % 50.0 23.1 0.105 RRT, % 33.3 15.4 0.272 Cr: Creatinine / Cl: Clearance / CR: Complete remission / PR: Partial remission / RRT: Renal replacement therapy Table 2: Renal outcomes of patients with LN class IV-G crescentic versus not crescentic . Crescentic IV-GN=18 . Not Crescentic IV-GN=26 . p-value . Follow-up, months 22.0±25.7 31.3±24.4 0.059 Serum Cr, mg/dl 2.7±2.0 2.0±2.4 0.083 CrCl, ml/min/1,73m2 40.0±28.3 62.0±31.7 0.046 CR, % 6.3 42.3 0.030 PR, % 68.8 38.5 0.010 Doubling Cr, % 72.2 30.8 0.013 CrCl < 30 ml/min/1,73m2, % 50.0 23.1 0.105 RRT, % 33.3 15.4 0.272 . Crescentic IV-GN=18 . Not Crescentic IV-GN=26 . p-value . Follow-up, months 22.0±25.7 31.3±24.4 0.059 Serum Cr, mg/dl 2.7±2.0 2.0±2.4 0.083 CrCl, ml/min/1,73m2 40.0±28.3 62.0±31.7 0.046 CR, % 6.3 42.3 0.030 PR, % 68.8 38.5 0.010 Doubling Cr, % 72.2 30.8 0.013 CrCl < 30 ml/min/1,73m2, % 50.0 23.1 0.105 RRT, % 33.3 15.4 0.272 Cr: Creatinine / Cl: Clearance / CR: Complete remission / PR: Partial remission / RRT: Renal replacement therapy Conclusions: We found clinical differences between class IV-G LN crescentic and not crescentic, but none pathological distinction was detected. Patients with biopsy proven crescentic LN had more rapidly progressive glomerulonephritis clinically, with a worse baseline creatinine clearance and a higher risk of renal disease progression. MP354URINARY LEVELS OF INFLAMMATORY, PROFIBROGENIC AND KIDNEY SELF-DEFENSE FACTORS IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS (CGN) Natalia Neprintseva Natalia Neprintseva 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Natalia Tchebotareva Natalia Tchebotareva 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Irina Bobkova Irina Bobkova 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Lidiya Kozlovskaya Lidiya Kozlovskaya 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Abstract Introduction and Aims: During CGN, a number of mediators are released from infiltrating and resident cells, leading to kidney inflammation, apoptosis and fibrosis. Many protective molecules are produced in response to injury and play an important role in the kidney self-control of damage. The balance between offence and defense factors determines CGN regression or progression.Our study aim was to assess urinary excretion of inflammatory, profibrogenic and kidney self-defense factors in patients (pts) with different CGN course. Methods: 53 active CGN pts were studied: 23 - with proteinuria (PU) 1-3 g/d (I group), 30 - with nephrotic syndrome (NS) (II group), including 7 pts with severe NS (anasarca, PU to 12 g/d, hypoalbuminemia < 20 g/L), and 7 pts - with NS and impaired renal function. Urinary level of inflammatory interleukin-6 (IL-6), a main profibrogenic growth factor TGF-β, apoptosis biomarker caspase-9 (CSP-9), anti-inflammatory factors IL-10 and IL-1 receptors antagonist (IL-1Ra), vessel endothelial growth factor (VEGF) and protective heat shock proteins (HSP-27 and HSP-70) were measured by ELISA. Results: Urinary excretion of IL-6 and TGF-β in pts with NS was significantly increased compared to I CGN group (tab.1). In severe NS urinary levels of these cytokines were higher than in moderate NS. Exactly in CGN with NS we revealed elevated CSP-9 in the urine, reflecting local renal apoptosis activation (tab.1).With offense factors in NS (especially severe) was increased the urinary excretion of anti-inflammatory IL-1Ra (tab.2). But in progressive CGN course (NS and renal failure) their levels were decreased (0,4 [0,11;0,73] ng/ml p<0,05), they negatively correlated with serum creatinine (Rs= -0,22, p<0,05). In active CGN without NS we revealed only trace quantities of urinary IL-10, in pts with NS its level was undetectable (tab.1).Protective HSP-27 and HSP-70 urinary levels were significantly higher in pts with NS compared to I group (tab.2). These indices correlated directly with urinary IL-6 (Rs=0,44, p<0,05 and Rs=0,59, p<0,05) and PU (Rs=0,27, p<0,05 and Rs=0,26, p<0,1) and negatively with serum albumin (Rs = -0,22, p<0,05 and Rs= -0,42, p<0,05). In CGN pts with severe NS urinary excretion of HSP were higher than in moderate NS (tab.2).Urinary level of VEGF (as survival factor that reflecting the glomerular permeability) was raised in CGN with NS compared to I group. It was the highest in severe NS (tab.2) and directly correlated with PU (Rs=0,673, p<0,01). But in progressive CGN course its level significantly decreased, negatively correlated with serum creatinine (Rs= -0,763, p<0,05). Conclusions: Determination of disturbances between injurious and glomerular self-defense factors in the urine may be useful to assess CGN activity and prognosis. Table 1 (*p<0,05 compared to I group; **p<0,05 compared to moderate NS) CGN pts group . IL-6 (ng/ml) . TGF-β (pg/ml) . CSP-9 (ng/ml) . IL-10 (ng/ml) . I (n=23) PU 1-3 g/d 5,44 [1,3; 12,8] 1,1 [0,4;2,2] 31,4 [31,3; 32,35] 0,1 [0; 1,1] II (n=30) NS 9,97 [1,95;25,6]* 1,65 [0,7;2,4]* 33,1 [32,0; 34,1]* 0 Moderate NS 9,21 [0,45; 16,38] 1,3 [0,7; 2,3] 32,5 [31,8; 33,9] 0 Severe NS 11,2 [2,61; 82,9]** 3,0 [2,2;4,6]** 33,7 [32,0; 34,4] 0 CGN pts group . IL-6 (ng/ml) . TGF-β (pg/ml) . CSP-9 (ng/ml) . IL-10 (ng/ml) . I (n=23) PU 1-3 g/d 5,44 [1,3; 12,8] 1,1 [0,4;2,2] 31,4 [31,3; 32,35] 0,1 [0; 1,1] II (n=30) NS 9,97 [1,95;25,6]* 1,65 [0,7;2,4]* 33,1 [32,0; 34,1]* 0 Moderate NS 9,21 [0,45; 16,38] 1,3 [0,7; 2,3] 32,5 [31,8; 33,9] 0 Severe NS 11,2 [2,61; 82,9]** 3,0 [2,2;4,6]** 33,7 [32,0; 34,4] 0 Table 1 (*p<0,05 compared to I group; **p<0,05 compared to moderate NS) CGN pts group . IL-6 (ng/ml) . TGF-β (pg/ml) . CSP-9 (ng/ml) . IL-10 (ng/ml) . I (n=23) PU 1-3 g/d 5,44 [1,3; 12,8] 1,1 [0,4;2,2] 31,4 [31,3; 32,35] 0,1 [0; 1,1] II (n=30) NS 9,97 [1,95;25,6]* 1,65 [0,7;2,4]* 33,1 [32,0; 34,1]* 0 Moderate NS 9,21 [0,45; 16,38] 1,3 [0,7; 2,3] 32,5 [31,8; 33,9] 0 Severe NS 11,2 [2,61; 82,9]** 3,0 [2,2;4,6]** 33,7 [32,0; 34,4] 0 CGN pts group . IL-6 (ng/ml) . TGF-β (pg/ml) . CSP-9 (ng/ml) . IL-10 (ng/ml) . I (n=23) PU 1-3 g/d 5,44 [1,3; 12,8] 1,1 [0,4;2,2] 31,4 [31,3; 32,35] 0,1 [0; 1,1] II (n=30) NS 9,97 [1,95;25,6]* 1,65 [0,7;2,4]* 33,1 [32,0; 34,1]* 0 Moderate NS 9,21 [0,45; 16,38] 1,3 [0,7; 2,3] 32,5 [31,8; 33,9] 0 Severe NS 11,2 [2,61; 82,9]** 3,0 [2,2;4,6]** 33,7 [32,0; 34,4] 0 Table 2 (*p<0,05 compared to I group; **p<0,05 compared to moderate NS) CGN pts group . IL-1Ra (ng/ml) . HSP-27 (ng/ml) . HSP-70 (ng/ml) . VEGF (pg/ml) . I (n=23)PU 1-3g/d 0,46 [0,08;0,82] 0,76 [0,68;1,14] 0,43 [0,41;0,45] 185,7 [163,8; 259,8] II (n=30) NS 1,22[1,16;2,85]* 1,1[0,73; 1,83]* 0,46 [0,43;0,50]* 300,15 [224,5;547,3] * Moderate NS 0,5[0,07;3,32] 0,84 [0,71; 1,81] 0,43 [0,41;0,51] 260,5 [183,95; 279,2] Severe NS 1,34[0,34;2,27]** 1,35 [0,93; 4,02]** 0,6 [0,5; 2,5]** 939,6 [824,2; 1049,5]** CGN pts group . IL-1Ra (ng/ml) . HSP-27 (ng/ml) . HSP-70 (ng/ml) . VEGF (pg/ml) . I (n=23)PU 1-3g/d 0,46 [0,08;0,82] 0,76 [0,68;1,14] 0,43 [0,41;0,45] 185,7 [163,8; 259,8] II (n=30) NS 1,22[1,16;2,85]* 1,1[0,73; 1,83]* 0,46 [0,43;0,50]* 300,15 [224,5;547,3] * Moderate NS 0,5[0,07;3,32] 0,84 [0,71; 1,81] 0,43 [0,41;0,51] 260,5 [183,95; 279,2] Severe NS 1,34[0,34;2,27]** 1,35 [0,93; 4,02]** 0,6 [0,5; 2,5]** 939,6 [824,2; 1049,5]** Table 2 (*p<0,05 compared to I group; **p<0,05 compared to moderate NS) CGN pts group . IL-1Ra (ng/ml) . HSP-27 (ng/ml) . HSP-70 (ng/ml) . VEGF (pg/ml) . I (n=23)PU 1-3g/d 0,46 [0,08;0,82] 0,76 [0,68;1,14] 0,43 [0,41;0,45] 185,7 [163,8; 259,8] II (n=30) NS 1,22[1,16;2,85]* 1,1[0,73; 1,83]* 0,46 [0,43;0,50]* 300,15 [224,5;547,3] * Moderate NS 0,5[0,07;3,32] 0,84 [0,71; 1,81] 0,43 [0,41;0,51] 260,5 [183,95; 279,2] Severe NS 1,34[0,34;2,27]** 1,35 [0,93; 4,02]** 0,6 [0,5; 2,5]** 939,6 [824,2; 1049,5]** CGN pts group . IL-1Ra (ng/ml) . HSP-27 (ng/ml) . HSP-70 (ng/ml) . VEGF (pg/ml) . I (n=23)PU 1-3g/d 0,46 [0,08;0,82] 0,76 [0,68;1,14] 0,43 [0,41;0,45] 185,7 [163,8; 259,8] II (n=30) NS 1,22[1,16;2,85]* 1,1[0,73; 1,83]* 0,46 [0,43;0,50]* 300,15 [224,5;547,3] * Moderate NS 0,5[0,07;3,32] 0,84 [0,71; 1,81] 0,43 [0,41;0,51] 260,5 [183,95; 279,2] Severe NS 1,34[0,34;2,27]** 1,35 [0,93; 4,02]** 0,6 [0,5; 2,5]** 939,6 [824,2; 1049,5]** MP355SIGNIFICANCE OF URINARY NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS A BIOMARKER OF DISEASE ACTIVITY IN PATIENTS WITH LUPUS NEPHRITIS Violeta Rabrenović Violeta Rabrenović 1 Military Medical Academy, Belgrade, Serbia Zoran KovačEvić Zoran KovačEvić 1 Military Medical Academy, Belgrade, Serbia Dragan Jovanović Dragan Jovanović 1 Military Medical Academy, Belgrade, Serbia Milorad Rabrenović Milorad Rabrenović 1 Military Medical Academy, Belgrade, Serbia Svetlana Antić Svetlana Antić 1 Military Medical Academy, Belgrade, Serbia Ljiljana Ignjatović Ljiljana Ignjatović 1 Military Medical Academy, Belgrade, Serbia Milica Petrović Milica Petrović 1 Military Medical Academy, Belgrade, Serbia Abstract Introduction and Aims: Neutrophil gelatinase associated lipocalin is small protein expressed in neutrophils and different epithelia just as are renal proximal tubule. Its role in early diagnosis of acute renal failure is well known, and there are studies which indicate that it could have potentially significant role as biomarker of activity of lupus nefritis.The aim of this study was to compare the level of urinary Neutrophil gelatinase associated lipocalin (uNGAL) in the group of patients with active lupus nephritis (LN), with group with lupus nephritis in remission and to determine the correlation of uNGAL level with paramers of disease activity. Methods: The prospective study included a group of 40 patients, homogeneous in terms of demographic data (gender, age, body weight) and type of lupus nephritis and therapeutic modality; 20 were associated with lupus nephritis in remission and 20 with active disease. We compared the parameters of groups in 3 visits over 2 months: kreatinine/s,albumin/s, C3, C4, ANA ,dsDNA antibodies, SLEDAI/r score, proteinuria, urinary protein/creatinine ratio-Upr/Cr, uNGAL. All patients had creatinine clearance ≥ 60 ml/min. U NGAL was determined by immunochemical test (Abbott). Results: A statistically significant difference (p <0.001) between group 1A ( active LN) and 2R( LN in remis) was observed for the comparison of anti dsDNA antibodies, proteinuria, Upr/cre, SLEDAI/r score, uNGAL The uNGAL was significantly correlated with parameters of active disease (p <0.001) - SLEDAI/r scor, proteinuria, Upr/cr. The values of the area under the ROC curve (AUC) the maximum sensitivity of 95% sensitivity and 100% specificity expressed in u NGAL. The coordinates of the ROC curve for the uNGAL, limit "cut off" was 52.95 ng/ml. All patients with uNGAL more than 52.95 ng / ml, should be in the group with active disease, and none in the group with lupus nephritis in remission. Conclusions: The results show that level of uNGAL is significant in monitoring disease activity as well as in confirmation of remission, thus enabling more appropriate individual approach to treatment. Therefore, uNGAL can be a used as in daily clinical practice, and can contribute to positive outcome of treatment. MP356RITUXIMAB THERAPY IN PATIENTS WITH PRIMARY AND SECONDARY GLOMERULONEPHRITIS: RELATIONSHIP BETWEEN CLINICAL RESPONSE AND CD19+ TREND Selena Longhi Selena Longhi 1 A. Manzoni Hospital, Lecco, Italy Lucia Del Vecchio Lucia Del Vecchio 1 A. Manzoni Hospital, Lecco, Italy Sara Viganò Sara Viganò 1 A. Manzoni Hospital, Lecco, Italy Donatella Casartelli Donatella Casartelli 1 A. Manzoni Hospital, Lecco, Italy Maria Carla Bigi Maria Carla Bigi 1 A. Manzoni Hospital, Lecco, Italy Mauro Corti Mauro Corti 1 A. Manzoni Hospital, Lecco, Italy Monica Limardo Monica Limardo 1 A. Manzoni Hospital, Lecco, Italy Flavia Tentori Flavia Tentori 1 A. Manzoni Hospital, Lecco, Italy Giuseppe Pontoriero Giuseppe Pontoriero 1 A. Manzoni Hospital, Lecco, Italy Abstract Introduction and Aims: Rituximab has been shown to be an effective therapy in a number of primary glomerulonephritis and in immune-mediated systemic disease with renal involvement. Once administered with the schedule used in lymphoma (i.e. 4 administrations, 375 mg/m2), more recently it is administered as a single administration or using the rheumatologic dose regimen (2 administrations, 1 g). However, it is still unclear whether a single administration obtaining complete CD 19+ depletion may be enough to obtain a significant clinical response. Moreover, little is known for how long CD19+ persists following the single administration. Methods: Single centre, retrospective analysis of 18 patients (9 M/ 9 F; mean age 60.96 ± 14.21 years), treated with Rituximab in single or multiple dose for a variety of conditions (Membranous glomerulonephritis = 6; ANCA associated vasculitis = 3; Lupus nephritis = 3; HCV positive cryoglobulinemia = 5, focal segmental glomerular sclerosis = 1) between June 2009 and December 2013 (median follow up of 12.6 months, range 1.56 - 47.03 months). CD 19+ levels, serum creatinine, proteinuria and clinical manifestations of systemic disease were collected at baseline (first Rituximab administration) and during follow-up. Results: Rituximab therapy was decided because of refractory disease to more traditional therapies and absolute or relative contraindications. Patients received from one to four Rituximab infusions (mean 1.77) according to clinical needs and CD19+ trend over time. 4 patients received a rheumatologic dosing regimen. The mean dose for each Rituximab administration was 738.47 mg. with a mean cumulative dose of 991.45 mg (min 375 mg, max 3400 mg).Complete CD19+ depletion (CD19+ < 5 cell/mm3) was obtained in all the patients; CD19+ returned to values ≥ 5 cell/mm3 in 13 patients after a mean of 7.87 months (min 3.6, max 19.9 months). In one patient with cryoglobulinemia, who was treated with 3 doses of Rituximab, complete CD19+ depletion was persistent during the whole follow-up.The trend of CD19+ was related to clinical manifestations in 9 out of 16 patients (two patients were excluded for inconclusive data).Treatment response (defined as significant improvement of clinical manifestations of the disease and/or proteinuria decrease and/or improvement in renal function) was obtained in 13 out of 16 patients.Drug administration was complicated by fever in one patient and atrial fibrillation in another one. 4 patients developed pneumonia following Rituximab administration and one patient had severe sepsis. One patient had a syncope two weeks after drug administration. Conclusions: Rituximab is an effective treatment option in adult patients suffering from primary and secondary glomerulonephritis. According to our limited experience, CD19+ depletion cannot always predict patient response to Rituximab and/or disease relapses, even if in some patients increased CD19+ levels may anticipate disease relapses. MP357COMPARISON OF SERUM URIC ACID BETWEEN LUPUS PATIENTS WITH AND WITHOUT LUPUS NEPHRITIS Abbas Ali Zeraati Abbas Ali Zeraati 1 Kidney Transplantation Complications Research Center, Mashhad University of Medical Sciences, Mashhad, Iran, Islamic Republic of Zhaleh Shariati Sarabi Zhaleh Shariati Sarabi 2 Mashhad University of Medical Sciences, Mashhad, Iran, Islamic Republic of Amir Davoudabadi Farahani Amir Davoudabadi Farahani 3 Kidney Transplantation Complications Research Center, Mashhad, Iran, Islamic Republic of Zahra Mirfeizi Zahra Mirfeizi 2 Mashhad University of Medical Sciences, Mashhad, Iran, Islamic Republic of Abstract Introduction and Aims: Generally it has been reported that hyperuricemia has correlation with initiation and progression of renal disease in human being studies. This correlation between hyperuricemia and development of lupus nephritis has still remained unclear. The goal of the present study is to assess and evaluate the role of serum uric acid (UA) in diagnosis of lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients. Methods: In this cross- sectional study, one hundred lupus patients (six males and ninety-four females) were divided into two groups entitled 1-lupus patients with nephritis, 2-lupus patients without nephritis. Serum uric acid (UA), C3, C4, ANA, and Anti ds DNA were measured and SLEDAI score calculated. Man -Whitney Test, Spearman’s Correlation and ROC Curve were used for data analysis. Results: Serum uric acid levels in Lupus nephritis were significantly higher than that in non lupus nephritis (P value=0.03). In total patients, serum uric acid levels positively correlated with ANA, Anti ds DNA, SLEDAI-2K scores and correlated negatively with C3, c4. In lupus patients without nephritis, serum UA levels positively correlated with ANA, Anti ds DNA and negatively correlated with C3. However, in patients with LN, serum UA levels negatively correlated with C3. The area under the ROC curve was 0.875 with a 95% confidence interval of 0.804 to 0.946 (P=0.0001)(Figure1). Serum UA >4.95 mg/dl discriminates LN with sensitivity, specificity and accuracy of 77%, 82% and 87.5% respectively. Conclusions: The most important clinical conclusion in this study is that measurement of serum UA may result in earlier diagnosis of lupus nephritis. Open in new tabDownload slide Open in new tabDownload slide MP358CHARACTERISTICS OF THE RENAL RENIN ANGIOTEINSIN SYSTEM IN EXPERIMENTAL ALPORT’S SYNDROME Eunhui Bae Eunhui Bae 1 Departments of Medicine and Institute of Medical Science, University of Toronto, Toronto, ON, Canada Abstract Introduction and Aims: Alport’s syndrome (AS) is a hereditary nephropathy which is caused by mutations in type IV collagen genes, leading to end-stage renal disease. It has been reported that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers have protective effects for AS induced nephropathy. However, intrarenal alteration of RAS components in AS have not been fully elucidated. Methods: Intrarenal renin-angiotensin system (RAS) components were evaluated in 4- (early stage) and 7-wk (disease manifestation stage) wild-type (WT) and Col4A3 KO mice. Results: Proteinuria, tubulointerstitial fibrosis and glomerulosclerosis were markedly increased in 7-wk Col4 KO mice. The protein expression of renin, angiotensinogen, angiotension type 1 receptor, and Mas receptor was increased in 7-wk Col4 KO mice compared to 7-wk WT. The protein expression of angiotension converting enzyme (ACE) and ACE2 was decreased in 7-wk Col4 KO mice compared to 7-wk WT. Intrarenal Ang II peptide level was not changed between two groups in 4- and 7-wk mice, while Ang-(1-7) peptide level was markedly decreased in 7-wk Col4 KO mice compared to 7-wk WT. In 4-wk mice, there were no significant changes in RAS components protein expression, between two groups except renin expression. The renin expression was markedly decreased in 4-wk Col4 KO mice compared to 4-wk WT. Conclusions: In conclusion, decreased ACE2 and Ang-(1-7) in the kidney may play a major role in pathogenesis of AS-induced nephropathy. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
TI - PRIMARY AND SECONDARY GLOMERULONEPHRITIDES 2
JF - Nephrology Dialysis Transplantation
DO - 10.1093/ndt/gfu170
DA - 2014-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/primary-and-secondary-glomerulonephritides-2-GD0cUpTfhg
SP - iii434
EP - iii447
VL - 29
IS - suppl_3
DP - DeepDyve
ER -