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

Background: Decreased kidney function is commonly caused by hypovolemia. When hypovolemic, the kidney reabsorbs water resulting in concentrated urine. Osmolality is a measure of urine concentration which is more objective than self-reported fluid intake. It has a positive association with hypovolemia. However, it remains controversial whether osmolality is associated with decreased kidney function and/or albuminuria.

Methods: We conducted a cross-sectional analysis of the 2009-2012 National Health and Nutrition Examination Survey, a standardized survey in the U.S.

Population: Participants aged 18-70 years old with random urine osmolality were included. Osmolality was categorized as quartiles. Decreased kidney function was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m² and albuminuria was defined by albumin-to-creatinine ratio ≥ 30 mg/gm. We performed multivariable regression via four sequential models.

Results: Our study sample included 7,373 participants. The mean age was 42.9 ± 0.4 years. Overall, 51.4% were male and 67.3% were white. The mean osmolality was 603.8 mOsm/kg and 629.1 mOsm/kg in those with and without decreased eGFR and/or albuminuria, respectively. The number of cases was 610 (6.7%). The prevalence from the lowest to highest quartiles of osmolality was 116 (6.2%), 213 (8.6%), 179 (7.5%), and 102 (4.3%), respectively (p-value for trend = 0.02). The relationship between osmolality and eGFR appeared nonlinear. After adjustment for demographic, social, cardiovascular, and dietary risk factors, there was no significant association of osmolality quartiles with decreased eGFR and/or albuminuria (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.56, 1.07). In sensitivity analyses, osmolality ≥ 500 mOsm/kg was associated with lower eGFR (adjusted ß -1.13, 95% CI -1.98, -0.28). In pre-specified subgroup analyses, osmolality had a statistically significant negative correlation with eGFR among individuals with eGFR ≥ 60 mL/min/1.73m², but a positive correlation among those with eGFR < 60 mL/min/1.73m² (adjusted ß -0.19, 95% CI -0.36, -0.01 versus adjusted ß 0.50, 95% CI 0.05, 0.96; p-value for interaction = 0.016).

Conclusions: Higher osmolality was significantly associated with lower eGFR among adults with eGFR ≥ 60 mL/min/1.73m² Future research should examine the relationship between osmolality and change in kidney function over time among adults with normal eGFR.