Presentation description

Chronic kidney disease (CKD) is a morbid condition associated with a high risk of death. Diabetes and hypertension are the most common causes of CKD, and preventing CKD will benefit patients and society. Prior studies have linked a higher dietary acid load, quantified by a higher urinary ammonium (NH4+) level, with progression to kidney failure in patients with CKD. We previously showed that higher NH4+ was associated with higher urinary levels of transforming growth factor-beta1 (TGF-beta1), a measure of kidney fibrosis, in patients with CKD. This study aimed to expand this finding to patients without CKD. We studied 184 US veterans with diabetes and/or hypertension but no history of CKD. Urinary NH4+ was measured via formalin-titration and urinary TGF-beta1 and kidney injury molecule-1 (KIM-1), a marker of kidney tubule damage, were measured by enzyme-linked immune-sorbent assay. We performed log-log linear regression model to determine the association between urinary NH4+ and urinary TGF-beta1 and KIM-1 after adjusting for age, sex, body mass index, systolic blood pressure, estimated glomerular filtration rate, urine albumin/creatinine, hemoglobin A1c, cardiovascular disease, and urine creatinine (to account for urinary concentration). After adjustment, urinary NH4+ was positively associated with urinary KIM-1 and TGF-beta1. Each 1% increase in urinary NH4+ was associated with 0.5% (95% CI, 0.2-0.9, p=0.01) higher urinary KIM-1 and 0.8% (95% CI, 0.1-1.6, p=0.04) higher urinary TGF-beta1. Our results suggest that higher urinary NH4+ is associated with kidney damage in individuals at high-risk for CKD. Interventions that lower urinary NH4+ by lowering dietary acid load could be a useful strategy to prevent CKD in high-risk individuals.