Background Lower urine pH has been associated with reduced kidney function and an increased risk of kidney disease; however, its prognostic and pathological significance in biopsy–proven kidney disease remains unclear. A recent study demonstrated that medullary cast formation is independently associated with adverse renal outcomes beyond established predictors such as interstitial fibrosis and tubular atrophy (IFTA), yet its clinical determinants are not fully elucidated. Urine pH reflects the intratubular acid–base microenvironment and may contribute to tubular obstruction through cast formation. In this study, we examined kidney outcomes in patients undergoing native kidney biopsy, and the associations of urine pH with medullary cast formation.

Methods Among 1,167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included in this retrospective observational cohort study. 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 The mean baseline eGFR was 54.3±17.7 mL/min/1.73 m², the mean urine pH was 6.15±0.84, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the kidney outcome. Kaplan–Meier analysis showed that lower urine pH was associated with a higher risk of kidney outcomes. In Cox proportional hazards models adjusted for proteinuria, baseline eGFR, and IFTA score, urine pH remained independently associated with kidney outcomes (hazard ratio, 0.69; 95% confidence interval, 0.51–0.91). Inclusion of urine pH improved prognostic discrimination beyond established risk factors (Harrell’s C-index, 0.642 to 0.654). Lower urine pH was also associated with greater medullary cast formation.

Conclusion In patients undergoing native kidney biopsy, lower urine pH was independently associated with adverse kidney outcomes and greater medullary cast formation.

The authors have declared no competing interest.

This work was supported by the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (C) (grant no. 24K11411).

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The Institutional Review Board of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences gave ethical approval for this work.

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