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 in identifying those at greater risk of 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 kidney disease (ESRD). StudyDesign. Prospective longitudinal cohort study. Setting and participants. 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. Predictor. Fasting urinary osmolality (Uosm) measured by delta cryoscopy. Outcomes. End-stage renal disease (ESRD), mortality prior to ESRD, and measured GFR (mGFR) assessed by 51 Cr-EDTA renal clearance. Analytical Approach. Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death prior to 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 and a median fasting Uosm of 502.7 ± 151.7 mOsm/kg H2O. Baseline fasting Uosm was strongly associated with mGFR (R=0.54, p<0.001). 380 ESRD events and 225 deaths prior to ESRD occurred during a median follow-up of 5.9 years [3.8-8.2]. Patients with lower baseline fasting Uosm had a higher adjusted risk of 4ESRD but not of mortality (HRs of 1.9 [95% CI, 1.2-3.0] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest versus highest tertile). Based on a mixed linear model, adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline Uosm had a steeper decline in kidney function (-4.9% ± 0.9% per year, p<0.001) compared to patients in the highest tertile.Limitations. Fasting was self-reported.Conclusions. Fasting Uosm may be a useful tool, in addition to GFR and albuminuria, for assessing non-glomerular damage in patients with CKD who are at higher risk of CKD progression.

Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria

“…Elevated levels of vasopressin have been reported in individuals with confirmed nephrogenic diabetes insipidus associated with lithium (24). This feature of near normal urine concentrating ability and elevated vasopressin or copeptin (the surrogate marker of vasopressin) levels has been reported in other conditions such as polycystic kidney disease (PKD) (25,26), and during chronic kidney disease (27), during which a decrease in urine concentrating ability is predictive of a steeper decline in mGFR and of ESKD (28). As it is known to play an important role in the pathophysiology of cyst growth in PKD and some authors suggest a deleterious role in CKD as well (29,30), one could hypothesize that it might also be an important mediator of lithium-induced tubulo-interstitial and microcystic kidney disease.…”

The association of urine osmolality with decreased kidney function and/or albuminuria in the United States

“…in 2003 demonstrated low urine osmolality is an independent risk factor for reduced kidney function regardless of polycystic kidney disease (PKD) [ 11 ]. Recently, two prospective studies using urine osmolality tertiles, conducted in 2019 by the French NephroTest Study Group [ 12 ] ( N = 2,084; mean age 58.7 ± 15.2 years; 67.7% male; mean urine osmolality 502.7 ± 151.7 mOsm/kg; median baseline GFR 40.2 mL/min/1.73m 2 with interquartile range of 29.1–54.5) and Lee et al from the Korean Cohort Study on the Outcome of Chronic Kidney Disease Patients (KNOW-CKD) [ 13 ] ( N = 1,999; mean age 53.8 ± 12.1 years; 61% males; mean baseline eGFR 50.3 ± 30.0 mL/min/1.73m 2 ) demonstrated that low urine osmolality was associated with a higher risk of kidney impairment and there was a significant interaction between urine osmolality and eGFR. These are consistent with the findings in our subgroup with eGFR < 60 mL/min/1.73m 2 ( N = 172, 2.3%; mean age 59.5 ± 0.6 years; 45.6% male; mean urine osmolality 559.2 ± 21.8 mOsm/kg; mean eGFR 52.0 ± 0.6 mL/min/1.73m 2 ).…”

The role of fractional excretion of sodium and urinary osmolality in Acute Kidney Injury in liver transplant

“…Additionally, 6 hours after LT, osmolality predicted 60-day mortality with a median of 354 in the survivor group vs 534 in the non-survivor group with a p 0,004 and an AUC 0,21 (CI 0,07-0,34). The multicentre study reported by Tabzadeh et al with 2084 patients concluded that osmolality, in addition to GFR and albuminuria, is a useful tool for assessing non-glomerular damage in patients with CKD 18 .…”