Association between ratio of measured extracellular volume to expected body fluid volume and renal outcomes in patients with chronic kidney disease: a retrospective single-center cohort study

BACKGROUND: Excess extracellular volume is a major clinical problem in patients with chronic kidney disease (CKD). However, whether the extracellular volume status is associated with disease progression is unclear. We investigated the association between the extracellular volume status and renal outcomes. METHODS: We performed a retrospective cohort study of 149 patients with CKD who underwent bioelectrical impedance analysis (BIA) from 2005 to 2009. Patients were categorized according to tertiles of extracellular volume status. The extracellular volume status was assessed by examining the ratio of extracellular water measured by BIA (ECWBIA) to the total body water calculated using the Watson formula (TBWWatson). The main outcomes were adverse renal outcomes as defined by a decline of ≥50% from the baseline glomerular filtration rate or initiation of renal replacement therapy. RESULTS: A higher %ECWBIA/TBWWatson ratio tended to be associated with older age, male sex, diabetes mellitus, resistant hypertension, lower renal function, lower serum albumin levels, higher proteinuria levels, and a higher frequency of furosemide use. In the multivariate analysis, proteinuria remained independently associated with the %ECWBIA/TBWWatson ratio. Both the intracellular and extracellular water volumes decreased with age (correlation between ICW and age, r=-0.30, P<0.001; correlation between ECW and age, r=-0.17, P=0.03). Consequently, the %ECWBIA in the body fluid composition increased with age. During a median follow-up of 4.9 years, patients in the highest tertile of the %ECWBIA/TBWWatson ratio were at greater risk of adverse renal outcomes (16.6 per 100.0 patient years) than were those in the lowest tertile (8.1 per 100.0 patient years) or second tertile (5.6 per 100.0 patient years) (log-rank P=0.005). After adjustment for covariates, the %ECWBIA/TBWWatson ratio was significantly associated with adverse renal outcomes (hazard ratio, 1.21; 95 % confidence interval, 1.10-1.34; P<0.001). CONCLUSIONS: The ECWBIA/TBWWatson ratio was independently associated with adverse renal outcomes. Proteinuria was independently associated with the extracellular volume status. The balance between ICW and ECW changes with age in that the percentage of ECW content in the body fluid composition increases. Elderly patients with CKD may thus be susceptible to volume overload.