Association between Urine Ammonium and Urine TGF-β1 in CKD

Abstract

Background and objectivesUrinary ammonium excretion increases in response to nonvolatile acids to maintain normal systemic bicarbonate and pH. However, enhanced ammonia production promotes tubulointerstitial fibrosis in animal models. Therefore, a subset of individuals with CKD and normal bicarbonate may have acid-mediated kidney fibrosis that might be better linked with ammonium excretion than bicarbonate. We hypothesized that urine TGF-β1, as an indicator of kidney fibrosis, would be more tightly linked with urine ammonium excretion than serum bicarbonate and other acid-base indicators.Design, setting, participants, & measurementsWe measured serum bicarbonate and urinary ammonium, titratable acids, pH, and TGF-β1/creatinine in 144 persons with CKD. Multivariable-adjusted linear regression models determined the cross-sectional association between TGF-β1/creatinine and serum bicarbonate, urine ammonium excretion, urine titratable acids excretion, and urine pH.ResultsMean eGFR was 42 ml/min per 1.73 m2, mean age was 65 years old, 78% were men, and 62% had diabetes. Mean urinary TGF-β1/creatinine was 102 (49) ng/g, mean ammonium excretion was 1.27 (0.72) mEq/h, mean titratable acids excretion was 1.14 (0.65) mEq/h, mean urine pH was 5.6 (0.5), and mean serum bicarbonate was 23 (3) mEq/L. After adjusting for eGFR, proteinuria, and other potential confounders, each SD increase of urine ammonium and urine pH was associated with a statistically significant 1.22-fold (95% confidence interval, 1.11 to 1.35) or 1.11-fold (95% confidence interval, 1.02 to 1.21) higher geometric mean urine TGF-β1/creatinine, respectively. Each SD increase of serum bicarbonate and urine titratable acids was associated with a nonsignificant 1.06-fold (95% confidence interval, 0.97 to 1.16) or 1.03-fold (95% confidence interval, 0.92 to 1.14) higher geometric mean urine TGF-β1/creatinine, respectively.ConclusionsUrinary ammonium excretion but not serum bicarbonate is associated with higher urine TGF-β1/creatinine.