Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Abstract

Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).

Study design: Prospective longitudinal cohort study.

Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.

Predictor: Fasting urinary osmolality measured using delta cryoscopy.

Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using ⁵¹Cr-EDTA renal clearance.

Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.

Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m² and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H₂O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.

Limitations: Fasting was self-reported.

Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.

Keywords: CKD progression; GFR decline; Urine osmolality; biomarker; chronic kidney disease (CKD); end-stage renal disease (ESRD); glomerular filtration rate (GFR); measured GFR (mGFR); prognostic factor; tubular damage; urine concentration ability.