Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease

Any grade of relative overhydration is associated with long-term mortality in patients with... Clinical Kidney Journal, 2018, vol. 11, no. 3, 372–376 doi: 10.1093/ckj/sfy018 Advance Access Publication Date: 28 March 2018 Original Article ORIGI N AL A R TICLE Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease Almudena Vega, Soraya Abad, Nicola ´ s Macı ´as, Ine ´ s Aragoncillo, Ana Garcı ´a-Prieto, Tania Linares, Esther Torres, Andre ´ s Herna ´ ndez and Jose´Luno Nephrology Department, Hospital General Universitario Gregorio Marano ~ ´ n, Madrid, Spain Correspondence and offprint requests to: Almudena Vega; E-mail: vega.almudena@gmail.com; Twitter handle: @almudenavega1 ABSTRACT Background: Overhydration (OH) is associated with mortality in chronic kidney disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW) measured by bioimpedance >15% has shown an increased mortality risk in haemodialysis but few studies have been developed in advanced CKD. Our objective was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non-dialysis CKD. Methods: We performed a prospective study of 356 patients enrolled in 2011 and followed up until 2016. At baseline we collected general characteristics, serum inflammatory and nutrition markers, cardiovascular events (CVEs) and body composition using bioimpedance spectroscopy. During a median follow-up of 50 (24–66) months we collected mortality data. Results: The mean creatinine was 3.56 1.3 mg/dL, median proteinuria was 0.5 [interquartile range (IQR) 0.2–1.5] g/24 h, median OH was 0.6 (IQR 0.4–1.5) L and mean relative OH (OH/ECW) was 2.36 0.8%. We found that 32% of patients died. The univariate Cox analysis showed an association between mortality and age, diabetes, previous CVEs, Charlson comorbidity index, low albumin and pre-albumin, high C-reactive protein (CRP), low lean tissue and high OH/ECW. Multivariate Cox analysis confirmed an association between mortality and age {exp(B) 1.1 [95% confidence interval (CI) 1.0–1.3]; P¼ 0.001}, Charlson comorbidity index [exp(B) 1.1 (95% CI 1.0–1.2); P¼ 0.01], CRP [exp(B) 1.1 (95% CI 1.0–1.2); P¼ 0.04], OH/ECW [exp(B) 3.18 (95% CI 2.09–4.97); P¼ 0.031] and low lean tissue [exp(B) 0.82 (95% CI 0.69–0.98); P¼ 0.002]. Kaplan–Meier analysis confirmed higher mortality in patients with OH/ECW>0% (log rank 11.1; P¼ 0.001). Conclusion: Any grade of relative OH measured by OH/ECW>0% is associated with long-term mortality in patients with Stage 4 or 5 non-dialysis CKD. Keywords: bioimpedance, cardiovascular events, chronic kidney disease, mortality, overhydration Received: 22.11.2017. Editorial decision: 6.2.2018 V C The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 Relative overhydration in CKD | 373 Fluid status was assessed at baseline using BIS (body compo- INTRODUCTION sition monitor, Fresenius Medical Care, Bad Homburg, Patients with advanced chronic kidney disease (CKD) have an Germany). Measurements were taken after a 10-min resting increased risk of developing cardiovascular events (CVEs) and period in the supine position. Hydration parameters were total mortality [1, 2]. Chronic fluid overload has been shown to be a body water [TBW (in litres)], ECW (in litres), intracellular water mortality and morbidity risk factor in patients undergoing hae- [ICW (in litres)] and fluid overload [OH (in litres)], defined as modialysis [3, 4]. An association between fluid overload and water not included in extracellular and intracellular spaces and morbidity in CKD has also been reported [5–7]. However, hydra- considered as excess water. We estimated relative OH by divid- tion status may be difficult to assess due to the imprecision of ing OH by ECW (OH/ECW) [6]. We also collected lean tissue index clinical findings such as arterial hypertension, pulmonary and 2 2 [LTI (in kg/m )] and fat tissue index [FTI (in kg/m )] data. peripheral oedema and heart failure, which is not always pre- Laboratory variables recorded included creatinine and glom- sent on examination. Therefore, objective tools to estimate hy- erular filtration rate (MDRD4 equation), proteinuria, N-terminal dration status and body composition are needed. Bioimpedance prohormone of brain natriuretic peptide (NT-proBNP), nutri- spectroscopy (BIS) is a simple and non-invasive technique based tional and inflammatory parameters (pre-albumin and albu- on tissue resistance to the flow of an alternating current ranging min), and C-reactive protein (CRP). from 5 to 1000 kHz in frequency [8–11]. It has been validated using reference methods. BIS is therefore a useful and reliable tool for assessing body composition and hydration status [12–14]. Follow-up BIS allows one to estimate overhydration adjusted for extra- During follow-up {50 [interquartile range (IQR) 24–66] months}, cellular water (OH/ECW). Values >15% have been shown to be a new CVEs and mortality were recorded. CVEs were defined as risk factor for mortality and morbidity in patients on haemo- ischaemic or haemorrhagic cerebrovascular accident (diagnosed dialysis [3]. A study demonstrated an association between fluid by computed tomography), myocardial infarction (diagnosed by overload and traditional and novel risk factors for CV disease cardiac marker elevation and electrocardiography and con- such as inflammation, proteinuria, male sex, age or diabetes in firmed by coronary angiography), CHF (diagnosed by the pres- the CKD population [15]. Another study showed an association ence of acute pulmonary oedema and an echocardiogram with between relative overhydration >7% and mortality in patients ventricular systolic dysfunction and left ventricular ejection with advanced CKD [7]. fraction<45%) and peripheral vascular events (diagnosed by The objective of this study was to evaluate the effect of OH stenosis of major arteries or lower limbs confirmed by arteriog- on mortality in patients with Stage 4 or 5 non-dialysis CKD. raphy and/or the need for amputation). Mortality aetiology was classified as CV, tumoural, infection, rejection to start renal replacement therapy and other. MATERIALS AND METHODS Design of the study Statistical analysis This is a prospective study that started in January 2011 and pa- All variables were analysed using a Kolmogorov–Smirnov test to tients were followed up until December 2016. Variables were classify them as normally or non-normally distributed. Values collected at the beginning of the study and at the end of the are given as mean 6 SD or median (IQR). Univariate analysis study we collected mortality data. Patients who started renal re- was performed using logistic regression to assess factors associ- placement therapy during follow-up were excluded. ated with mortality and CVEs. A multivariate Cox regression analysis was performed in order to establish independent pre- Study population dictors of mortality and CVEs. The models included factors that showed a significant association or those considered confound- A total of 370 Stage 4 or 5 non-dialysis CKD patients were en- ing factors. Outcomes were analysed using Kaplan–Meier plots rolled in this study at a single centre in Madrid, Spain. CKD was and survival curves were compared using a log-rank test. All defined and staged according to Kidney Disease Outcomes statistical analyses were performed with SPSS 18.0 software Quality Initiative guidelines using the Modification of Diet in (SPSS, Chicago, IL, USA). P-values <0.05 were considered statis- Renal Disease four-variable equation (MDRD4) [16]. Inclusion tically significant. criteria were clinical stability with no recent hospitalization in the past 3 months, outpatient follow-up for >3 months, age >18 years and informed consent obtained. Exclusion criteria RESULTS were an inability to understand the study, contraindication to BIS (patients with pacemakers or limb amputation), loss of la- Baseline characteristics boratory parameters or loss to follow-up. Of these, 17 patients We included 356 patients; 64% were male with a mean age of were finally excluded. 676 13 years. Baseline characteristics are shown in Table 1. The mean creatinine was 3.56 1.3 mg/dL, mean glomerular filtration Baseline variables rate (MDRD equation) was 16 mL/min/1.73 m and median pro- At baseline, demographic and clinical data were collected, teinuria was 0.5 (IQR 0.2–1.5) g/24 h. Forty-three percent of pa- including age, sex, CKD aetiology, presence of diabetes melli- tients were receiving diuretics. The median OH was 0.6 (IQR tus, hypertension (defined using the Eighth Report of the Joint 0.4–1.5) L and mean relative OH (OH/ECW) was 2.36 0.8%. The National Committee) [17], dyslipidaemia (defined using Adult percentage of patients with a lower mean relative OH (OH/ Treatment Panel III guidelines) [18], Charlson comorbidity ECW<2.36 0.8%) was 44% and the percentage with a higher index [19] and a history of prior heart disease including con- mean relative OH (OH/ECW>2.36 0.8%) was 56%. gestive heart failure (CHF) and myocardial infarction, periph- A total of 236 patients (66%) had relative OH (OH/ECW) >0% eral vascular disease (PVD) and stroke. and 120 patients (34%) had a relative OH (OH/ECW) <0%. Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 374 | A. Vega et al. Table 1. Baseline characteristics of the study population (n5 356) The univariate Cox analysis showed an association between mortality and age, diabetes, Charlson comorbidity index, previ- Characteristics Value ous CVE, low albumin level, low pre-albumin, high levels of CRP, high OH, low LTI and high OH/ECW (Table 2). Multivariate Cox General characteristics (%) analysis showed an independent association with mortality and Sex (male) 64 age, Charlson comorbidity index, higher CRP levels, low LTI and Age (years), mean6 SD 676 13 relative OH (OH/ECW) as seen in Table 2. We divided patients Charlson comorbidity index, mean6 SD 7.26 2.7 into two groups (OH/ECW<0% and OH/ECW>0%). Kaplan–Meier Diabetes 36 Hypertension 87 analysis confirmed higher mortality in patients with OH/ Dyslipidaemia 72 ECW>0% (log rank 11.1; P¼ 0.001) as seen in Figure 1. CKD aetiology (%) Glomerular 23 Start of renal replacement therapy Diabetes 19 Vascular 28 A total of 125 patients (35%) needed dialysis during follow-up. Interstitial 13 Polycystic 10 Other 7 DISCUSSION Previous CVE (%) This study shows that any grade of relative OH in patients with Myocardial Infarction 28 advanced CKD is a long-term independent mortality risk factor. CHF 27 Thus minimal OH, even difficult to detect on examination, is Stroke 15 related to mortality. The majority of studies related to OH and Peripheral vascular disease (%) 12 mortality have been performed in patients receiving renal re- Laboratory parameters placement therapy. Wizemann et al. [9] studied the relation be- Creatinine (mg/dL), mean6 SD 3.56 1.5 tween relative OH and mortality in patients receiving chronic MDRD (mL/min/1.73 m ), mean6 SD 16.06 5.5 haemodialysis and established a cut-off of relative overhydra- Proteinuria (g/24 h), median (IQR) 0.5 (0.2–1.5) tion >15%. We found in a transverse study in haemodialysis pa- Albumin (g/dL), mean6 SD 4.16 0.4 NT-proBNP (ng/dL), median (IQR) 84 (37–181) tients an association between CVEs and relative OH. This CRP (mg/dL), median (IQR) 0.3 (0.1–0.7) association was maintained even when we decreased the cut- Pre-albumin (mg/dL), median (IQR) 32 (27–38) off to 10% [20]. In patients receiving peritoneal dialysis, the Hydration statement and corporal composition same association between mortality and relative OH >15% has BMI (kg/m ), mean6 SD 28.06 5.2 been found, so this association could not be dependent on the FTI (kg/m ), mean6 SD 12.36 5.6 type of renal replacement therapy chosen by patients [21]. Tsai LTI (kg/m ), mean6 SD 15.76 3.4 et al.[7] studied relative OH in advanced CKD non-dialysis pa- OH (L), median (IQR) 0.6 (0.4–1.5) tients and found a significant cut-off for mortality of 7%. Based ECW (L), mean6 SD 17.06 3.5 on our results, we propose to decrease the cut-off to as low as ICW (L), mean6 SD 19.76 4.7 possible, because any degree of relative OH in CKD is harmful ECW/ICW, mean6 SD 0.86 0.1 and, if possible, should be avoided. OH/ECW (%), mean6 SD 2.36 0.8 The most common mortality cause in advanced CKD, as in our group of patients, is CV. Some known CV factors (traditional BMI, body mass index; CHF, congestive heart failure; CKD, chronic kidney dis- and novel ones), such as male sex, age and diabetes, are associ- ease; CRP, C-reactive protein; ECW, extracellular water; FTI, fat tissue index; ICW, intracellular water; LTI, lean tissue index; MDRD, MDRD equation to esti- ated and increase in prevalence with overhydration. All of these, mate glomerular filtration rate; Nt-ProBNP, N-terminal prohormone of brain including inflammatory and cardiac biomarkers and a history of natriuretic peptide; OH, overhydration; PVD, Peripheral vascular disease. CV disease have been demonstrated as independent risk factors for CVEs and mortality in the CKD population [22–24]. The main CVEs at the end of follow-up finding of this study is that OH by itself is also an independent long-term mortality risk factor. Therefore BIS can help detect A total of 150 patients (42%) experienced a CVE during follow- high-risk patients, as it is an easy and useful tool [17]. Probably, up. The most common CVE was CHF (47%), as well as myocar- and although our study lacks serial measurements, performing dial infarction (28%), peripheral vascular disease (13%) and cere- BIS more frequently, for example, at each clinical visit, could im- brovascular accident (12%). prove patient survival [25]. Those patients with OH could then re- Univariate analysis showed that older age, diabetes, hyper- ceive closer follow-up, adjusting diuretics if necessary and tension, dyslipidaemia, previous CVE, higher Charlson comor- receiving more frequent visits to the nephrologist. bidity index, proteinuria, CRP, NT-proBNP levels, lower albumin Body composition may influence mortality in advanced CKD as levels and impaired kidney function were associated with CVEs. we previously described [26]. Low LTI is associated with mortality. Multivariate analysis confirmed an independent association be- Lean tissue is related to physical activity, so we encourage our pa- tween proteinuria [exp(B) 1.1; P¼ 0.001], CRP [exp(B) B 1.2; tients to practice exercise regularly. Other significant factors such as P¼ 0.02], NT-proBNP [exp(B) 1.2; P¼ 0.01], impaired kidney func- age, Charlson comorbidity index and high levels of CRP are frequent tion [exp(B) 0.7; P¼ 0.03] and previous CVEs [exp(B) 2.7; P¼ 0.001] variables related to mortality in the general population and in CKD and development of CVEs during follow-up. [27, 28]. Another interesting finding is that the association between mortality and other risk factor such as previous CVEs, diabetes and Mortality low pre-albumin level were not significant in our study and relative We found that 113 patients (32%) died during follow-up. OH and low lean tissue had an independent association. Mortality causes were CV, 19%; tumoural, 7%; infections, 3%; CVEs were recorded in 150 patients. Nearly half of these conservative treatment, 1% and other, 2%. patients had CHF, and this frequent association contributes Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 Relative overhydration in CKD | 375 FIGURE 1: Kaplan–Meier analysis for mortality and relative OH. Log rank 11.1; P ¼ 0.001. Table 2. Cox proportional hazards regression analysis for mortality Univariate Multivariate Baseline characteristics HR (95% CI) P-value HR (95% CI) P-value Sex (male, %) 1.35 (0.76–1.79) 0.34 Age (years) 1.08 (1.01–1.20) 0.001 1.1 (1.0–1.3) 0.001 Diabetes (%) 1.50 (1.20–1.98) 0.024 1.30 (0.62–1.87) 0.32 Hypertension (%) 1.65 (0.33–1.98) 0.76 Dyslipidaemia (%) 1.43 (0.54–1.87) 0.45 Charlson comorbidity index 1.27 (1.03–1.74) 0.02 1.1 (1.0–1.2) 0.01 Previous global CVEs 1.50 (1.19–1.99) 0.001 1.59 (0.89–3.30) 0.26 Creatinine (mg/dL) 1.02 (0.89–1.18) 0.34 Proteinuria (g/24 h) 1.001 (0.99–1.01) 0.69 Albumin (g/dL) 0.38 (0.12–0.79) 0.001 0.84 (0.68–1.12) 0.54 Prealbumin (mg/dL) 0.94 (0.56–0.99) 0.001 0.99 (0.89–1.23) 0.31 CRP (mg/dL) 1.20 (1.03–1.78) 0.01 1.3 (1.1–1.9) 0.04 NT-proBNP (ng/dL) 1.00 (0.99–1.01) 0.677 Cholesterol 0.99 (0.98–1.01) 0.07 OH (L) 1.1 (1.02–1.19) 0.01 1.10 (0.99–1.20) 0.08 ECW (L) 0.96 (0.88–1.05) 0.640 ICW (L) 0.88 (0.81–1.04) 0.12 OH/ECW (%) 3.10 (1.88–5.01) 0.001 3.18 (2.09–4.97) 0.031 BMI (kg/m ) 0.98 (0.93–1.04) 0.650 FTI (kg/m ) 1.04 (0.89–1.08) 0.124 LTI (kg/m ) 0.85 (0.33–0.97) 0.001 0.82 (0.69–0.98) 0.002 Bold significance is for P-values <0.05. BMI, body mass index; CRP, C-reactive protein; CVev, cardiovascular events; ECW, extracellular water; FTI, fat tissue index; ICW, intracellular water; LTI, lean tissue index; Nt-ProBNP, N-terminal prohormone of brain natriuretic peptide; OH, overhydration; OH/ECW, Relation between overhydration and extracellular water. to the development of cardiorenal syndrome, which explains study. As regards mortality, CVEs were also the most import- the morbidity of this association [29]. A significant number of ant cause of death. For these reasons, we suggest that new patients suffered from myocardial infarction. Chronic disease strategies to detect early CVEs should be developed to improve has been shown to increase mortality in patients with ischae- the survival of our CKD patients. Meanwhile, the use of BIS to mic heart disease [30]. Monitoring of serum cardiac biomarkers monitor fluid overload may be helpful. may therefore be helpful to detect these conditions, as NT- Our study has some limitations. Only one BIS measurement proBNP was associated to the development of CVEs in our was available for each patient and no additional BIS Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 376 | A. Vega et al. 13. Kotanko P, Levin W, Zhu F. Current state of bioimpedance tech- measurements could be done to evaluate their changes and consequences. We did not measure urine sodium and sodium nologies in dialysis. NephrolDialTransplant 2008; 23: 808–812 intake, which could be involved in oedema formation. 14. Basile C, Vernaglione L, Di Iorio B et al. Development and val- In conclusion, any grade of relative OH measured by OH/ idation of bioimpedance analysis prediction equations for dry weight in hemodialysis patients. Clin J Am Soc Nephrol ECW>0% is associated with long-term mortality in patients with Stages 4 and 5 CKD. 2007; 2: 675–680 15. Hung S-C, Kuo K-L, Peng C-H et al. Volume overload correl- ates with cardiovascular risk factors in patients with chronic ACKNOWLEDGEMENTS kidney disease. Kidney Int 2014; 85: 703–709 16. Levey AS, Coresh J, Greene T et al. Using standardized serum The authors would like to thank Thomas O’Boyle for proof- creatinine values in the modification of diet in renal disease reading the manuscript. study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247–254 AUTHORS’ CONTRIBUTIONS 17. James PA, Oparil S, Carter BL et al. 2014 evidence-based guide- line for the management of high blood pressure in adults: re- A.V., S.A., I.A., N.M. and J.L. designed the study. A.G-P., T.L., port from the panel members appointed to the Eighth Joint E.T. and A.H. performed BIS. N.M. gave informed consent. National Committee (JNC 8). JAMA 2014; 311: 507–520 A.V., S.A. and I.A. collected data. A.V. wrote the manuscript. 18. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third CONFLICT OF INTEREST STATEMENT Report of the National Cholesterol Education Program (NCEP) None declared. The authors alone are responsible for the Expert Panel on Detection, Evaluation, and Treatment of High content and writing of this paper. Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143–3421 19. Charlson M, Szatrowski TP, Peterson J et al. Validation of a com- REFERENCES bined comorbidity index. J Clin Epidemiol 1994; 47: 1245–1251 1. Holzmann M, Jernberg T, Szummer K et al. Long-term cardio- 20. Vega A, Quiroga B, Abad S et al. Study on overhydration in vascular outcomes in patients with chronic kidney disease dialysis patients and its association with inflammation. undergoing coronary artery bypass graft surgery for acute Nefrologia 2014; 34: 579–583 coronary syndromes. J Am Heart Assoc 2014; 3: e000707 21. Jotterand Drepper V, Kihm LP, Ka ¨lble F et al. Overhydration is a strong predictor of mortality in peritoneal dialysis patients - 2. Betriu A, Martinez-Alonso M, Arcidiacono MV et al. Prevalence of subclinical atheromatosis and associated risk independently of cardiac failure. PLoS One 2016; 11: e0158741 factors in chronic kidney disease: the NEFRONA study. 22. Bae EH, Lim SY, Cho KH et al. GFR and cardiovascular out- Nephrol Dial Transplant 2013; 29: 1415–1422 comes after acute myocardial infarction: results from the Korea Acute Myocardial Infarction Registry. Am J Kidney Dis 3. Wizemann V, Wabel P, Chamney P et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial 2012; 59: 795–802 Transplant 2009; 24: 1574–1579 23. Lou Q-L, Ouyang X-J, Gu L-B et al. Chronic kidney disease and 4. Hecking M, Karaboyas A, Antlanger M et al. Significance of associated cardiovascular risk factors in Chinese with type 2 diabetes. Diabetes Metab J 2012; 36: 433–442 interdialytic weight gain versus chronic volume overload: consensus opinion. Am J Nephrol 2013; 38: 78–90 24. Agrawal V, Marinescu V, Agarwal M et al. Cardiovascular im- plications of proteinuria: an indicator of chronic kidney dis- 5. Caravaca F, Martı ´nez del Viejo C, Villa J et al.Hydration status assessment by multi-frequency bioimpedance in patients with ease. Nat Rev Cardiol 2009; 6: 301–311 advanced chronic kidney disease. Nefrologia 2011; 31: 537–44 25. Verdalles U, de Vinuesa SG, Goicoechea M et al. Utility of bio- 6. Tsai Y-C, Tsai J-C, Chiu Y-W et al. Is fluid overload more im- impedance spectroscopy (BIS) in the management of refrac- tory hypertension in patients with chronic kidney disease portant than diabetes in renal progression in late chronic kidney disease? PLoS One 2013; 8: e82566 (CKD). Nephrol Dial Transplant 2012; 27: iv31–iv35 7. Tsai YC, Chiu JC, Tsai JC et al. Association of fluid overload 26. Vega A, Abad S, Macı ´as N et al. Low lean tissue mass is an in- with cardiovascular morbidity and all-cause mortality in dependent risk factor for mortality in patients with stage 4 and 5 non-dialysis chronic kidney disease. Clin Kidney J 2017; stages 4 and 5 CKD. Clin J Am Soc Nephrol 2015; 10: 39–46 8. Chazot C, Wabel P, Chamney P et al. Importance of normohy- 10: 170–175 dration for the long-term survival of haemodialysis patients. 27. Gregg LP, Adams-Huet B, Li X et al. Effect modification of Nephrol Dial Transplant 2012; 27: 2404–2410 chronic kidney disease on the association of circulating and imaging cardiac biomarkers with outcomes. J Am Heart Assoc 9. Wizemann V, Rode C, Wabel P. Whole-body spectroscopy (BCM) in the assessment of normovolemia in hemodialysis 2017; 6: e005235 28. Doi T, Yamamoto S, Morinaga T et al. Risk score to predict patients. Contrib Nephrol 2008; 161: 115–118 10. Machek P, Jirka T, Moissl U et al. Guided optimization of fluid 1-year mortality after haemodialysis initiation in patients status in haemodialysis patients. Nephrol Dial Transplant with stage 5 chronic kidney disease under predialysis neph- 2010; 25: 538–544 rology care. PLoS One 2015; 10: e0129180 29. Ronco C, Di Lullo L. Cardiorenal syndrome. Heart Fail Clin 11. Earthman C, Traughber D, Dobratz J et al. Bioimpedance spectroscopy for clinical assessment of fluid distribution 2014; 10: 251–280 and body cell mass. Nutr Clin Pract 2007; 22: 389–405 30. Sabroe JE, Thayssen P, Antonsen L et al. Impact of renal insuf- 12. Wabel P, Chamney P, Moissl U et al. Importance of whole ficiency on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous cor- body bioimpedance spectroscopy for the management of the fluid balance. Blood Purif 2009; 27: 75–80 onary intervention. BMC Cardiovasc Disord 2014; 14: 15 Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Kidney Journal Oxford University Press

Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease

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Clinical Kidney Journal, 2018, vol. 11, no. 3, 372–376 doi: 10.1093/ckj/sfy018 Advance Access Publication Date: 28 March 2018 Original Article ORIGI N AL A R TICLE Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease Almudena Vega, Soraya Abad, Nicola ´ s Macı ´as, Ine ´ s Aragoncillo, Ana Garcı ´a-Prieto, Tania Linares, Esther Torres, Andre ´ s Herna ´ ndez and Jose´Luno Nephrology Department, Hospital General Universitario Gregorio Marano ~ ´ n, Madrid, Spain Correspondence and offprint requests to: Almudena Vega; E-mail: vega.almudena@gmail.com; Twitter handle: @almudenavega1 ABSTRACT Background: Overhydration (OH) is associated with mortality in chronic kidney disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW) measured by bioimpedance >15% has shown an increased mortality risk in haemodialysis but few studies have been developed in advanced CKD. Our objective was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non-dialysis CKD. Methods: We performed a prospective study of 356 patients enrolled in 2011 and followed up until 2016. At baseline we collected general characteristics, serum inflammatory and nutrition markers, cardiovascular events (CVEs) and body composition using bioimpedance spectroscopy. During a median follow-up of 50 (24–66) months we collected mortality data. Results: The mean creatinine was 3.56 1.3 mg/dL, median proteinuria was 0.5 [interquartile range (IQR) 0.2–1.5] g/24 h, median OH was 0.6 (IQR 0.4–1.5) L and mean relative OH (OH/ECW) was 2.36 0.8%. We found that 32% of patients died. The univariate Cox analysis showed an association between mortality and age, diabetes, previous CVEs, Charlson comorbidity index, low albumin and pre-albumin, high C-reactive protein (CRP), low lean tissue and high OH/ECW. Multivariate Cox analysis confirmed an association between mortality and age {exp(B) 1.1 [95% confidence interval (CI) 1.0–1.3]; P¼ 0.001}, Charlson comorbidity index [exp(B) 1.1 (95% CI 1.0–1.2); P¼ 0.01], CRP [exp(B) 1.1 (95% CI 1.0–1.2); P¼ 0.04], OH/ECW [exp(B) 3.18 (95% CI 2.09–4.97); P¼ 0.031] and low lean tissue [exp(B) 0.82 (95% CI 0.69–0.98); P¼ 0.002]. Kaplan–Meier analysis confirmed higher mortality in patients with OH/ECW>0% (log rank 11.1; P¼ 0.001). Conclusion: Any grade of relative OH measured by OH/ECW>0% is associated with long-term mortality in patients with Stage 4 or 5 non-dialysis CKD. Keywords: bioimpedance, cardiovascular events, chronic kidney disease, mortality, overhydration Received: 22.11.2017. Editorial decision: 6.2.2018 V C The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 Relative overhydration in CKD | 373 Fluid status was assessed at baseline using BIS (body compo- INTRODUCTION sition monitor, Fresenius Medical Care, Bad Homburg, Patients with advanced chronic kidney disease (CKD) have an Germany). Measurements were taken after a 10-min resting increased risk of developing cardiovascular events (CVEs) and period in the supine position. Hydration parameters were total mortality [1, 2]. Chronic fluid overload has been shown to be a body water [TBW (in litres)], ECW (in litres), intracellular water mortality and morbidity risk factor in patients undergoing hae- [ICW (in litres)] and fluid overload [OH (in litres)], defined as modialysis [3, 4]. An association between fluid overload and water not included in extracellular and intracellular spaces and morbidity in CKD has also been reported [5–7]. However, hydra- considered as excess water. We estimated relative OH by divid- tion status may be difficult to assess due to the imprecision of ing OH by ECW (OH/ECW) [6]. We also collected lean tissue index clinical findings such as arterial hypertension, pulmonary and 2 2 [LTI (in kg/m )] and fat tissue index [FTI (in kg/m )] data. peripheral oedema and heart failure, which is not always pre- Laboratory variables recorded included creatinine and glom- sent on examination. Therefore, objective tools to estimate hy- erular filtration rate (MDRD4 equation), proteinuria, N-terminal dration status and body composition are needed. Bioimpedance prohormone of brain natriuretic peptide (NT-proBNP), nutri- spectroscopy (BIS) is a simple and non-invasive technique based tional and inflammatory parameters (pre-albumin and albu- on tissue resistance to the flow of an alternating current ranging min), and C-reactive protein (CRP). from 5 to 1000 kHz in frequency [8–11]. It has been validated using reference methods. BIS is therefore a useful and reliable tool for assessing body composition and hydration status [12–14]. Follow-up BIS allows one to estimate overhydration adjusted for extra- During follow-up {50 [interquartile range (IQR) 24–66] months}, cellular water (OH/ECW). Values >15% have been shown to be a new CVEs and mortality were recorded. CVEs were defined as risk factor for mortality and morbidity in patients on haemo- ischaemic or haemorrhagic cerebrovascular accident (diagnosed dialysis [3]. A study demonstrated an association between fluid by computed tomography), myocardial infarction (diagnosed by overload and traditional and novel risk factors for CV disease cardiac marker elevation and electrocardiography and con- such as inflammation, proteinuria, male sex, age or diabetes in firmed by coronary angiography), CHF (diagnosed by the pres- the CKD population [15]. Another study showed an association ence of acute pulmonary oedema and an echocardiogram with between relative overhydration >7% and mortality in patients ventricular systolic dysfunction and left ventricular ejection with advanced CKD [7]. fraction<45%) and peripheral vascular events (diagnosed by The objective of this study was to evaluate the effect of OH stenosis of major arteries or lower limbs confirmed by arteriog- on mortality in patients with Stage 4 or 5 non-dialysis CKD. raphy and/or the need for amputation). Mortality aetiology was classified as CV, tumoural, infection, rejection to start renal replacement therapy and other. MATERIALS AND METHODS Design of the study Statistical analysis This is a prospective study that started in January 2011 and pa- All variables were analysed using a Kolmogorov–Smirnov test to tients were followed up until December 2016. Variables were classify them as normally or non-normally distributed. Values collected at the beginning of the study and at the end of the are given as mean 6 SD or median (IQR). Univariate analysis study we collected mortality data. Patients who started renal re- was performed using logistic regression to assess factors associ- placement therapy during follow-up were excluded. ated with mortality and CVEs. A multivariate Cox regression analysis was performed in order to establish independent pre- Study population dictors of mortality and CVEs. The models included factors that showed a significant association or those considered confound- A total of 370 Stage 4 or 5 non-dialysis CKD patients were en- ing factors. Outcomes were analysed using Kaplan–Meier plots rolled in this study at a single centre in Madrid, Spain. CKD was and survival curves were compared using a log-rank test. All defined and staged according to Kidney Disease Outcomes statistical analyses were performed with SPSS 18.0 software Quality Initiative guidelines using the Modification of Diet in (SPSS, Chicago, IL, USA). P-values <0.05 were considered statis- Renal Disease four-variable equation (MDRD4) [16]. Inclusion tically significant. criteria were clinical stability with no recent hospitalization in the past 3 months, outpatient follow-up for >3 months, age >18 years and informed consent obtained. Exclusion criteria RESULTS were an inability to understand the study, contraindication to BIS (patients with pacemakers or limb amputation), loss of la- Baseline characteristics boratory parameters or loss to follow-up. Of these, 17 patients We included 356 patients; 64% were male with a mean age of were finally excluded. 676 13 years. Baseline characteristics are shown in Table 1. The mean creatinine was 3.56 1.3 mg/dL, mean glomerular filtration Baseline variables rate (MDRD equation) was 16 mL/min/1.73 m and median pro- At baseline, demographic and clinical data were collected, teinuria was 0.5 (IQR 0.2–1.5) g/24 h. Forty-three percent of pa- including age, sex, CKD aetiology, presence of diabetes melli- tients were receiving diuretics. The median OH was 0.6 (IQR tus, hypertension (defined using the Eighth Report of the Joint 0.4–1.5) L and mean relative OH (OH/ECW) was 2.36 0.8%. The National Committee) [17], dyslipidaemia (defined using Adult percentage of patients with a lower mean relative OH (OH/ Treatment Panel III guidelines) [18], Charlson comorbidity ECW<2.36 0.8%) was 44% and the percentage with a higher index [19] and a history of prior heart disease including con- mean relative OH (OH/ECW>2.36 0.8%) was 56%. gestive heart failure (CHF) and myocardial infarction, periph- A total of 236 patients (66%) had relative OH (OH/ECW) >0% eral vascular disease (PVD) and stroke. and 120 patients (34%) had a relative OH (OH/ECW) <0%. Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 374 | A. Vega et al. Table 1. Baseline characteristics of the study population (n5 356) The univariate Cox analysis showed an association between mortality and age, diabetes, Charlson comorbidity index, previ- Characteristics Value ous CVE, low albumin level, low pre-albumin, high levels of CRP, high OH, low LTI and high OH/ECW (Table 2). Multivariate Cox General characteristics (%) analysis showed an independent association with mortality and Sex (male) 64 age, Charlson comorbidity index, higher CRP levels, low LTI and Age (years), mean6 SD 676 13 relative OH (OH/ECW) as seen in Table 2. We divided patients Charlson comorbidity index, mean6 SD 7.26 2.7 into two groups (OH/ECW<0% and OH/ECW>0%). Kaplan–Meier Diabetes 36 Hypertension 87 analysis confirmed higher mortality in patients with OH/ Dyslipidaemia 72 ECW>0% (log rank 11.1; P¼ 0.001) as seen in Figure 1. CKD aetiology (%) Glomerular 23 Start of renal replacement therapy Diabetes 19 Vascular 28 A total of 125 patients (35%) needed dialysis during follow-up. Interstitial 13 Polycystic 10 Other 7 DISCUSSION Previous CVE (%) This study shows that any grade of relative OH in patients with Myocardial Infarction 28 advanced CKD is a long-term independent mortality risk factor. CHF 27 Thus minimal OH, even difficult to detect on examination, is Stroke 15 related to mortality. The majority of studies related to OH and Peripheral vascular disease (%) 12 mortality have been performed in patients receiving renal re- Laboratory parameters placement therapy. Wizemann et al. [9] studied the relation be- Creatinine (mg/dL), mean6 SD 3.56 1.5 tween relative OH and mortality in patients receiving chronic MDRD (mL/min/1.73 m ), mean6 SD 16.06 5.5 haemodialysis and established a cut-off of relative overhydra- Proteinuria (g/24 h), median (IQR) 0.5 (0.2–1.5) tion >15%. We found in a transverse study in haemodialysis pa- Albumin (g/dL), mean6 SD 4.16 0.4 NT-proBNP (ng/dL), median (IQR) 84 (37–181) tients an association between CVEs and relative OH. This CRP (mg/dL), median (IQR) 0.3 (0.1–0.7) association was maintained even when we decreased the cut- Pre-albumin (mg/dL), median (IQR) 32 (27–38) off to 10% [20]. In patients receiving peritoneal dialysis, the Hydration statement and corporal composition same association between mortality and relative OH >15% has BMI (kg/m ), mean6 SD 28.06 5.2 been found, so this association could not be dependent on the FTI (kg/m ), mean6 SD 12.36 5.6 type of renal replacement therapy chosen by patients [21]. Tsai LTI (kg/m ), mean6 SD 15.76 3.4 et al.[7] studied relative OH in advanced CKD non-dialysis pa- OH (L), median (IQR) 0.6 (0.4–1.5) tients and found a significant cut-off for mortality of 7%. Based ECW (L), mean6 SD 17.06 3.5 on our results, we propose to decrease the cut-off to as low as ICW (L), mean6 SD 19.76 4.7 possible, because any degree of relative OH in CKD is harmful ECW/ICW, mean6 SD 0.86 0.1 and, if possible, should be avoided. OH/ECW (%), mean6 SD 2.36 0.8 The most common mortality cause in advanced CKD, as in our group of patients, is CV. Some known CV factors (traditional BMI, body mass index; CHF, congestive heart failure; CKD, chronic kidney dis- and novel ones), such as male sex, age and diabetes, are associ- ease; CRP, C-reactive protein; ECW, extracellular water; FTI, fat tissue index; ICW, intracellular water; LTI, lean tissue index; MDRD, MDRD equation to esti- ated and increase in prevalence with overhydration. All of these, mate glomerular filtration rate; Nt-ProBNP, N-terminal prohormone of brain including inflammatory and cardiac biomarkers and a history of natriuretic peptide; OH, overhydration; PVD, Peripheral vascular disease. CV disease have been demonstrated as independent risk factors for CVEs and mortality in the CKD population [22–24]. The main CVEs at the end of follow-up finding of this study is that OH by itself is also an independent long-term mortality risk factor. Therefore BIS can help detect A total of 150 patients (42%) experienced a CVE during follow- high-risk patients, as it is an easy and useful tool [17]. Probably, up. The most common CVE was CHF (47%), as well as myocar- and although our study lacks serial measurements, performing dial infarction (28%), peripheral vascular disease (13%) and cere- BIS more frequently, for example, at each clinical visit, could im- brovascular accident (12%). prove patient survival [25]. Those patients with OH could then re- Univariate analysis showed that older age, diabetes, hyper- ceive closer follow-up, adjusting diuretics if necessary and tension, dyslipidaemia, previous CVE, higher Charlson comor- receiving more frequent visits to the nephrologist. bidity index, proteinuria, CRP, NT-proBNP levels, lower albumin Body composition may influence mortality in advanced CKD as levels and impaired kidney function were associated with CVEs. we previously described [26]. Low LTI is associated with mortality. Multivariate analysis confirmed an independent association be- Lean tissue is related to physical activity, so we encourage our pa- tween proteinuria [exp(B) 1.1; P¼ 0.001], CRP [exp(B) B 1.2; tients to practice exercise regularly. Other significant factors such as P¼ 0.02], NT-proBNP [exp(B) 1.2; P¼ 0.01], impaired kidney func- age, Charlson comorbidity index and high levels of CRP are frequent tion [exp(B) 0.7; P¼ 0.03] and previous CVEs [exp(B) 2.7; P¼ 0.001] variables related to mortality in the general population and in CKD and development of CVEs during follow-up. [27, 28]. Another interesting finding is that the association between mortality and other risk factor such as previous CVEs, diabetes and Mortality low pre-albumin level were not significant in our study and relative We found that 113 patients (32%) died during follow-up. OH and low lean tissue had an independent association. Mortality causes were CV, 19%; tumoural, 7%; infections, 3%; CVEs were recorded in 150 patients. Nearly half of these conservative treatment, 1% and other, 2%. patients had CHF, and this frequent association contributes Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 Relative overhydration in CKD | 375 FIGURE 1: Kaplan–Meier analysis for mortality and relative OH. Log rank 11.1; P ¼ 0.001. Table 2. Cox proportional hazards regression analysis for mortality Univariate Multivariate Baseline characteristics HR (95% CI) P-value HR (95% CI) P-value Sex (male, %) 1.35 (0.76–1.79) 0.34 Age (years) 1.08 (1.01–1.20) 0.001 1.1 (1.0–1.3) 0.001 Diabetes (%) 1.50 (1.20–1.98) 0.024 1.30 (0.62–1.87) 0.32 Hypertension (%) 1.65 (0.33–1.98) 0.76 Dyslipidaemia (%) 1.43 (0.54–1.87) 0.45 Charlson comorbidity index 1.27 (1.03–1.74) 0.02 1.1 (1.0–1.2) 0.01 Previous global CVEs 1.50 (1.19–1.99) 0.001 1.59 (0.89–3.30) 0.26 Creatinine (mg/dL) 1.02 (0.89–1.18) 0.34 Proteinuria (g/24 h) 1.001 (0.99–1.01) 0.69 Albumin (g/dL) 0.38 (0.12–0.79) 0.001 0.84 (0.68–1.12) 0.54 Prealbumin (mg/dL) 0.94 (0.56–0.99) 0.001 0.99 (0.89–1.23) 0.31 CRP (mg/dL) 1.20 (1.03–1.78) 0.01 1.3 (1.1–1.9) 0.04 NT-proBNP (ng/dL) 1.00 (0.99–1.01) 0.677 Cholesterol 0.99 (0.98–1.01) 0.07 OH (L) 1.1 (1.02–1.19) 0.01 1.10 (0.99–1.20) 0.08 ECW (L) 0.96 (0.88–1.05) 0.640 ICW (L) 0.88 (0.81–1.04) 0.12 OH/ECW (%) 3.10 (1.88–5.01) 0.001 3.18 (2.09–4.97) 0.031 BMI (kg/m ) 0.98 (0.93–1.04) 0.650 FTI (kg/m ) 1.04 (0.89–1.08) 0.124 LTI (kg/m ) 0.85 (0.33–0.97) 0.001 0.82 (0.69–0.98) 0.002 Bold significance is for P-values <0.05. BMI, body mass index; CRP, C-reactive protein; CVev, cardiovascular events; ECW, extracellular water; FTI, fat tissue index; ICW, intracellular water; LTI, lean tissue index; Nt-ProBNP, N-terminal prohormone of brain natriuretic peptide; OH, overhydration; OH/ECW, Relation between overhydration and extracellular water. to the development of cardiorenal syndrome, which explains study. As regards mortality, CVEs were also the most import- the morbidity of this association [29]. A significant number of ant cause of death. For these reasons, we suggest that new patients suffered from myocardial infarction. Chronic disease strategies to detect early CVEs should be developed to improve has been shown to increase mortality in patients with ischae- the survival of our CKD patients. Meanwhile, the use of BIS to mic heart disease [30]. Monitoring of serum cardiac biomarkers monitor fluid overload may be helpful. may therefore be helpful to detect these conditions, as NT- Our study has some limitations. Only one BIS measurement proBNP was associated to the development of CVEs in our was available for each patient and no additional BIS Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018 376 | A. Vega et al. 13. Kotanko P, Levin W, Zhu F. Current state of bioimpedance tech- measurements could be done to evaluate their changes and consequences. We did not measure urine sodium and sodium nologies in dialysis. NephrolDialTransplant 2008; 23: 808–812 intake, which could be involved in oedema formation. 14. Basile C, Vernaglione L, Di Iorio B et al. Development and val- In conclusion, any grade of relative OH measured by OH/ idation of bioimpedance analysis prediction equations for dry weight in hemodialysis patients. Clin J Am Soc Nephrol ECW>0% is associated with long-term mortality in patients with Stages 4 and 5 CKD. 2007; 2: 675–680 15. Hung S-C, Kuo K-L, Peng C-H et al. Volume overload correl- ates with cardiovascular risk factors in patients with chronic ACKNOWLEDGEMENTS kidney disease. Kidney Int 2014; 85: 703–709 16. Levey AS, Coresh J, Greene T et al. Using standardized serum The authors would like to thank Thomas O’Boyle for proof- creatinine values in the modification of diet in renal disease reading the manuscript. study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247–254 AUTHORS’ CONTRIBUTIONS 17. James PA, Oparil S, Carter BL et al. 2014 evidence-based guide- line for the management of high blood pressure in adults: re- A.V., S.A., I.A., N.M. and J.L. designed the study. A.G-P., T.L., port from the panel members appointed to the Eighth Joint E.T. and A.H. performed BIS. N.M. gave informed consent. National Committee (JNC 8). JAMA 2014; 311: 507–520 A.V., S.A. and I.A. collected data. A.V. wrote the manuscript. 18. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third CONFLICT OF INTEREST STATEMENT Report of the National Cholesterol Education Program (NCEP) None declared. The authors alone are responsible for the Expert Panel on Detection, Evaluation, and Treatment of High content and writing of this paper. Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143–3421 19. Charlson M, Szatrowski TP, Peterson J et al. Validation of a com- REFERENCES bined comorbidity index. J Clin Epidemiol 1994; 47: 1245–1251 1. Holzmann M, Jernberg T, Szummer K et al. Long-term cardio- 20. Vega A, Quiroga B, Abad S et al. Study on overhydration in vascular outcomes in patients with chronic kidney disease dialysis patients and its association with inflammation. undergoing coronary artery bypass graft surgery for acute Nefrologia 2014; 34: 579–583 coronary syndromes. J Am Heart Assoc 2014; 3: e000707 21. Jotterand Drepper V, Kihm LP, Ka ¨lble F et al. Overhydration is a strong predictor of mortality in peritoneal dialysis patients - 2. Betriu A, Martinez-Alonso M, Arcidiacono MV et al. Prevalence of subclinical atheromatosis and associated risk independently of cardiac failure. PLoS One 2016; 11: e0158741 factors in chronic kidney disease: the NEFRONA study. 22. Bae EH, Lim SY, Cho KH et al. GFR and cardiovascular out- Nephrol Dial Transplant 2013; 29: 1415–1422 comes after acute myocardial infarction: results from the Korea Acute Myocardial Infarction Registry. Am J Kidney Dis 3. Wizemann V, Wabel P, Chamney P et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial 2012; 59: 795–802 Transplant 2009; 24: 1574–1579 23. Lou Q-L, Ouyang X-J, Gu L-B et al. Chronic kidney disease and 4. Hecking M, Karaboyas A, Antlanger M et al. Significance of associated cardiovascular risk factors in Chinese with type 2 diabetes. Diabetes Metab J 2012; 36: 433–442 interdialytic weight gain versus chronic volume overload: consensus opinion. Am J Nephrol 2013; 38: 78–90 24. Agrawal V, Marinescu V, Agarwal M et al. Cardiovascular im- plications of proteinuria: an indicator of chronic kidney dis- 5. Caravaca F, Martı ´nez del Viejo C, Villa J et al.Hydration status assessment by multi-frequency bioimpedance in patients with ease. Nat Rev Cardiol 2009; 6: 301–311 advanced chronic kidney disease. Nefrologia 2011; 31: 537–44 25. Verdalles U, de Vinuesa SG, Goicoechea M et al. Utility of bio- 6. Tsai Y-C, Tsai J-C, Chiu Y-W et al. Is fluid overload more im- impedance spectroscopy (BIS) in the management of refrac- tory hypertension in patients with chronic kidney disease portant than diabetes in renal progression in late chronic kidney disease? PLoS One 2013; 8: e82566 (CKD). Nephrol Dial Transplant 2012; 27: iv31–iv35 7. Tsai YC, Chiu JC, Tsai JC et al. Association of fluid overload 26. Vega A, Abad S, Macı ´as N et al. Low lean tissue mass is an in- with cardiovascular morbidity and all-cause mortality in dependent risk factor for mortality in patients with stage 4 and 5 non-dialysis chronic kidney disease. Clin Kidney J 2017; stages 4 and 5 CKD. Clin J Am Soc Nephrol 2015; 10: 39–46 8. Chazot C, Wabel P, Chamney P et al. Importance of normohy- 10: 170–175 dration for the long-term survival of haemodialysis patients. 27. Gregg LP, Adams-Huet B, Li X et al. Effect modification of Nephrol Dial Transplant 2012; 27: 2404–2410 chronic kidney disease on the association of circulating and imaging cardiac biomarkers with outcomes. J Am Heart Assoc 9. Wizemann V, Rode C, Wabel P. Whole-body spectroscopy (BCM) in the assessment of normovolemia in hemodialysis 2017; 6: e005235 28. Doi T, Yamamoto S, Morinaga T et al. Risk score to predict patients. Contrib Nephrol 2008; 161: 115–118 10. Machek P, Jirka T, Moissl U et al. Guided optimization of fluid 1-year mortality after haemodialysis initiation in patients status in haemodialysis patients. Nephrol Dial Transplant with stage 5 chronic kidney disease under predialysis neph- 2010; 25: 538–544 rology care. PLoS One 2015; 10: e0129180 29. Ronco C, Di Lullo L. Cardiorenal syndrome. Heart Fail Clin 11. Earthman C, Traughber D, Dobratz J et al. Bioimpedance spectroscopy for clinical assessment of fluid distribution 2014; 10: 251–280 and body cell mass. Nutr Clin Pract 2007; 22: 389–405 30. Sabroe JE, Thayssen P, Antonsen L et al. Impact of renal insuf- 12. Wabel P, Chamney P, Moissl U et al. Importance of whole ficiency on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous cor- body bioimpedance spectroscopy for the management of the fluid balance. Blood Purif 2009; 27: 75–80 onary intervention. BMC Cardiovasc Disord 2014; 14: 15 Downloaded from https://academic.oup.com/ckj/article-abstract/11/3/372/4955950 by Ed 'DeepDyve' Gillespie user on 20 June 2018

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Clinical Kidney JournalOxford University Press

Published: Mar 28, 2018

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