Association Between Urine pH and Kidney Outcomes in Patients with Biopsy-Proven Kidney Disease

Background/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ≥40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52–0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression.