Abstract
RATIONALE & OBJECTIVE: Uromodulin (UMOD) is a kidney tubule biomarker that can be measured in blood and urine and may help identify persons with chronic kidney disease (CKD) at greater risk of progression. Whether blood or urine UMOD is more strongly associated with CKD progression is unknown. STUDY DESIGN: This was a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), in which an intensive systolic blood pressure target reduced risk of cardiovascular events and mortality. SETTING & POPULATION: A total of 2,302 SPRINT participants with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2). EXPOSURES: Plasma and urine UMOD measured at baseline. OUTCOMES: Acute kidney injury, 30% decline in eGFR, end-stage kidney disease, and annualized percentage change in eGFR. ANALYTICAL APPROACH: Cox proportional hazards (acute kidney injury, 30% eGFR decline, and end-stage kidney disease) and linear mixed models (annual percent eGFR change) were adjusted for baseline characteristics, including eGFR and albuminuria. RESULTS: Among included participants, mean age was 73 years, 41% were female, and median eGFR was 50 (interquartile range: 40-57) mL/min/1.73 m(2). Median plasma and urine UMOD levels were 17.2 μg/L and 6.5 mg/L, respectively. Plasma and urine UMOD had a Spearman correlation of 0.40. In fully adjusted models, each standard deviation higher plasma UMOD level was associated with lower risk of 30% eGFR decline (hazard ratio=0.84, 95% confidence interval 0.75-0.94) and slower percent annual eGFR decline (+0.58, 95% confidence interval +0.22 to +0.94). In contrast, urine UMOD levels had weaker associations with these outcomes that did not remain after adjustment for baseline eGFR, albuminuria, and other risk factors. CONCLUSIONS: Among persons with hypertension and CKD, plasma UMOD levels were associated with slower decline in eGFR and reduced risk of 30% eGFR decline after adjustment for demographic and clinical characteristics, whereas urine UMOD levels were not. When evaluating risk of kidney endpoints, plasma rather than urine may be the preferable specimen for UMOD measurement.