Association of fluid overload with cardiovascular morbidity and all-cause mortality in stages 4 and 5 CKD

Abstract

Background and objectives: Fluid overload is a common characteristic associated with renal progression in CKD. Additionally, fluid overload is an independent predictor of all-cause or cardiovascular mortality in patients on dialysis, but its influence on patients not on dialysis is uncertain. The aim of the study was to assess the relationship between the severity of fluid status and clinical outcomes in an advanced CKD cohort.

Design, setting, participants, & measurements: In total, 478 predialysis patients with stages 4 and 5 CKD in the integrated CKD care program were enrolled from January of 2011 to December of 2011 and followed-up until August of 2013. The clinical outcomes included cardiovascular morbidity and all-cause mortality. The relative hydration status (overhydration/extracellular water) was used as the presentation of the severity of fluid status and measured using a body composition monitor. Overhydration/extracellular water >7% was defined as fluid overload.

Results: Over a median follow-up period of 23.2 (12.6-26.4) months, 66 (13.8%) patients reached all-cause mortality or cardiovascular morbidity. The adjusted hazard ratio of the combined outcome of all-cause mortality or cardiovascular morbidity for every 1% higher overhydration/extracellular water was 1.08 (95% confidence interval, 1.04 to 1.12; P<0.001). The adjusted overhydration/extracellular water for the combined outcome of all-cause mortality or cardiovascular morbidity in participants with overhydration/extracellular water ≥7% compared with those with overhydration/extracellular water <7% was 1.93 (95% confidence interval, 1.01 to 3.69; P=0.04). In subgroup analysis, higher overhydration/extracellular water was consistently associated with increased risk for the combined outcome independent of diabetes, cardiovascular disease, and serum albumin. There was no significant interaction between all subgroups.

Conclusions: These findings suggest that fluid overload is an independent risk factor of the combined outcome of all-cause mortality or cardiovascular morbidity in patients with advanced CKD.

Keywords: CKD; cardiovascular disease; mortality.

Figure 1.

Kaplan–Meier survival curves for cardiovascular morbidity or all-cause mortality. (A) The combined outcome of all-cause mortality or cardiovascular morbidity. (B) Cardiovascular morbidity. (C) All-cause mortality. △HS, relative hydration status.

Figure 2.

Adjusted hazard ratios (HRs) for combined outcome, cardiovascular morbidity, and all-cause mortality per 1% greater relative hydration status in all participants stratified by sex, diabetes mellitus, cardiovascular disease (CVD), and serum albumin. Ratios were adjusted for age, sex, diabetes mellitus, CVD, diuretics use, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers use, β-blocker, calcium channel blocker use, eGFR, log urine protein-to-creatinine ratio, body mass index, serum albumin, log cholesterol, hemoglobin levels, and systolic BP. The median values of serum albumin and high-sensitivity C-reactive protein (hsCRP) are 3.8 g/dl and 1.3 mg/L, respectively. 95% CI, 95% confidence interval.