Urine Ammonium Concentrations and Cardiovascular and Kidney Outcomes in Systolic Blood Pressure Intervention Trial Participants with CKD

Abstract

Key Points Among nondiabetic individuals with hypertension and CKD, higher urine ammonium concentration is associated with higher risk of cardiovascular disease.Urine ammonium was not associated with all-cause mortality or CKD progression, AKI, or linear eGFR decline in the Systolic Blood Pressure Intervention Trial cohort. Background Impaired urine ammonium excretion is common in CKD and may identify risk of metabolic acidosis earlier than reductions in serum bicarbonate or pH and thus may have associations with cardiovascular disease (CVD) outcomes. We evaluated the association of urine ammonium with CVD and kidney outcomes among persons with hypertension and nondiabetic CKD enrolled in a trial of BP reduction. Methods We measured urine ammonium concentration in spot urine specimens collected at baseline among 2092 participants of the Systolic Blood Pressure Intervention Trial (SPRINT) with an eGFR <60 ml/min per 1.73 m2. We used multivariable-adjusted Cox models to evaluate associations of urine ammonium concentration with the SPRINT CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death), all-cause mortality, the SPRINT kidney composite outcome (50% kidney function decline, ESKD, or transplant), and AKI. Results At baseline, the mean (SD) age was 73 (9) years; 40% were female; and 25% were Black participants. The mean (SD) serum bicarbonate was 25.6 (2.8) mmol/L, median (interquartile range) urine ammonium concentration was 14.4 (9.5–23.1) mmol/L, and median (interquartile range) eGFR was 49 (39–55) ml/min per 1.73 m2. There were 255 CVD composite events, 143 deaths, 63 kidney composite events, and 146 AKI events during a median follow-up of 3.8 years. In multivariable models, each two-fold higher urinary ammonium concentration was associated with a 26% (95% confidence interval, 1.05 to 1.52) higher risk of the CVD composite, whereas there was no association with all-cause mortality, the SPRINT kidney composite outcome, or AKI. Conclusions Among nondiabetic individuals with hypertension and CKD, higher urine ammonium concentration is associated with higher risk of CVD. Further studies are needed to evaluate this association in other cohorts.