Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort

Abstract

Background: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. Main Results: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.

Mannose and glycine: Metabolites with potentially causal implications in chronic kidney disease pathogenesis

“…Notably, serum osmolality has emerged as an independent risk factor for CKD onset [ 52 ]. In a retrospective longitudinal investigation, a higher baseline urinary osmolality was found to be closely linked to an elevated risk of end-stage kidney disease [ 53 ].…”

Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study

“…There is no evidence that plasma vitamin C levels at 24 h were lower than baseline to suggest rebound scurvy might result. This reported study shows that renal injury does not occur even at the highest dose of 100 g. The transient rise in creatinine at the 100-g dose may be related to the IVC but more likely is related to the very high osmolarity of the infusate [ 29 – 31 ].…”