High urine volume and low urine osmolality are risk factors for faster progression of renal disease

Background: Increased fluid intake slows renal disease progression in animal models. The relevance of these findings to human renal disease is not clear, although increased fluid intake often is recommended to patients with chronic renal insufficiency. This study tested the hypothesis that urine volume, urine osmolality (Uosm), or both are significantly associated with glomerular filtration rate (GFR) decline in patients with chronic renal insufficiency. Methods: This is a retrospective analysis of Modification of Diet in Renal Disease (MDRD) study A patients with (N = 139) and without polycystic kidney disease (PKD; N = 442). The key outcome measure was GFR slope in relation to mean 24-hour urine volume and Uosm during follow-up in study A (mean, 2.3 years). Results.,The regression of GFR slope on mean follow-up 24-hour urine volume (adjusted for body surface area and MDRD diet and blood pressure group) showed that the greater the urine volume, the faster the GFR decline in patients both with and without PKD. For example, the difference in GFR slope for those with a mean follow-up 24-hour urine volume of 2.4 versus 1.4 L was -1.01 mL/min/y (confidence interval, -0.27 to -1.75) for patients without PKD and -1.20 mL/min/y (confidence interval, -0.06 to -2.34) for those with PKD. A similar but inverse relationship was shown between GFR decline and mean 24-hour Uosm in patients with (P = 0.01) and without PKD (P = 0.001). These associations remained significant after adjustment for 13 relevant baseline and follow-up covariates. Conclusion: Sustained high urine volume and low Uosm are independent risk factors for faster GFR decline in patients with chronic renal insufficiency. Thus, high fluid intake does not appear to slow renal disease progression in humans. We suggest that until better evidence becomes available, patients with chronic renal insufficiency should generally let their thirst guide fluid intake. The advice to avoid "pushing fluids" might be particularly important for patients with PKD.