Volume 91, Issue 5, Pages 1214-1223 (May 2017) Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort  Marijke J.E. Dekker, Daniele Marcelli, Bernard J. Canaud, Paola Carioni, Yuedong Wang, Aileen Grassmann, Constantijn J.A.M. Konings, Peter Kotanko, Karel M. Leunissen, Nathan W. Levin, Frank M. van der Sande, Xiaoling Ye, Vaibhav Maheshwari, Len A. Usvyat, Jeroen P. Kooman  Kidney International  Volume 91, Issue 5, Pages 1214-1223 (May 2017) DOI: 10.1016/j.kint.2016.12.008 Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 1 Study design. For this study we included patients of the European subset of the MONDO Initiative database, with at least 1 multifrequency bioimpedance spectroscopy (MF-BIS) measurement in the year 2011. The last MF-BIS measurement of this year was used as an anchor point. All MF-BIS measurements (including the last 1 of 2011), dialysis characteristics, and laboratory values of the 3 months prior to this last MF-BIS measurement were used to calculate the averages of baseline period 1. The same parameters of the 3 months after the last MF-BIS measurement in 2011 were used to calculate the averages of period 2. A comparison of the study cohort and excluded patients revealed that excluded patients were younger (64 vs. 66 years; P < 0.001), more frequently diabetic (19.9% vs. 17.7%; P < 0.001), and had a higher prevalence of catheter as dialysis access (23.6% vs. 15.6%, P < 0.001). The difference in body mass index was not statistically significant. C-reactive protein (CRP) levels were higher (median: 6.4 mg/l [2.60–15.80] vs. 5.2 mg/l [2.30–11.57]; P < 0.001). Predialysis fluid status was lower in the excluded patients (median +1.57 L [0.59–2.62] vs. +1.71 L [0.88–2.62]; P < 0.001). For more details, see the Supplemental Material A, a comparison between the study cohort and the excluded patient cohort. *No data available due to transfer to other clinics, kidney transplantation, modality switch, no reason for unavailable CRP, or MF-BIS measurements. **Predialysis fluid depletion was defined as the predialysis “overhydration” compartment reported below –1.1 L. Kidney International 2017 91, 1214-1223DOI: (10.1016/j.kint.2016.12.008) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 2 Survival curve of the adjusted hazard ratios for mortality in patient groups stratified by (a) predialysis and (b) postdialysis fluid status. Survival probabilities and hazard ratios (HR) from a Cox proportional hazards model adjusted for age, gender, dialysis vintage, access type (arteriovenous vs. catheter access), region, body mass index, normalized protein catabolic rate, ultrafiltration rate (<10 ml/h/kg, 10–13 ml/h/kg, or >13 ml/h/kg), diabetes mellitus, congestive heart failure, peripheral vascular disease, cerebrovascular disease, and the presence of a malignancy. (a) Fluid depletion (N = 239), HR: 2.03 (95% CI: 1.32–3.12); moderate fluid overload (N = 3444), HR: 1.64 (95% CI: 1.35–1.98); severe fluid overload (N = 2083), HR: 2.74 (95% CI: 2.25–3.35); extreme fluid overload (N = 356), HR: 4.23 (95% CI: 3.16–5.65). The reference group is patients with predialysis normovolemia (>–1.1 L to +1.1 L) (N = 2761). (b) Fluid depletion (N = 4693), HR: 0.74 (95% CI: 0.62–0.90); moderate fluid overload (N = 1047), HR: 1.72 (95% CI: 1.45–2.05); severe fluid overload (N = 370), HR: 2.62 (95% CI: 2.09–3.34); extreme fluid overload (N = 108), HR: 3.22 (95% CI: 2.16–4.80). Reference group are patients with postdialysis normovolemia (>–1.1 L to +1.1 L) (N = 2665). Kidney International 2017 91, 1214-1223DOI: (10.1016/j.kint.2016.12.008) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 3 Relation between pre- and postdialysis fluid status. The percentage of patients with a particular postdialysis fluid status stratified by predialysis fluid status. Kidney International 2017 91, 1214-1223DOI: (10.1016/j.kint.2016.12.008) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 4 Patients stratified by inflammation and predialysis fluid status. Dynamics of fluid status and inflammation (I) in the subset analysis. FO+ = predialysis > +2.5 L fluid overload (FO); FO– = predialysis fluid status > –1.1 L and < +2.5 L; I+ = C-reactive protein > 6.0 mg/L; I– = C-reactive protein ≤ 6.0 mg/L. Kidney International 2017 91, 1214-1223DOI: (10.1016/j.kint.2016.12.008) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 5 Dynamics of fluid status and inflammation and survival during 6-month follow-up. Surival probabilities and hazard ratios from a Cox proportional hazards model adjusted for age, gender, dialysis vintage, access type (arteriovenous vs. catheter access), region, body mass index, normalized protein catabolic rate, ultrafiltration rate (<10 ml/h/kg, 10–13 ml/h/kg, or >13 ml/h/kg), diabetes mellitus, congestive heart failure, peripheral vascular disease, cerebrovascular disease, and present malignancy. Kidney International 2017 91, 1214-1223DOI: (10.1016/j.kint.2016.12.008) Copyright © 2016 International Society of Nephrology Terms and Conditions