Prognostic Value of Renal Medullary Findings in Native Kidney Biopsy Assessment

Background: Renal biopsy plays a crucial role not only in diagnosing kidney diseases, but also in assessing disease activity and prognosis. While pathological parameters such as the Interstitial Fibrosis and Tubular Atrophy (IFTA) score have been established as prognostic indicators, pathological alterations in the renal medulla have remained unexplored. This study investigated the association between pathological findings in the renal medulla and renal prognosis. Methods: A retrospective cohort study was conducted on 763 patients who underwent native kidney biopsy at Okayama University Hospital between January 2011 and December 2018. A total of 342 patients were included after excluding those under 18 years of age, with an eGFR<15 mL/min/1.73 m2 at the time of biopsy, or with insufficient medullary tissue for evaluation. Medullary fibrosis, inflammatory cell infiltration, and cast formation were semi-quantitatively scored (0, 1 or 2) and their associations with composite renal outcomes (eGFR≥40% decline or initiation of renal replacement therapy) were examined. Results: The mean eGFR was 62.9 ± 26.2 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 3.0 years, 86 patients reached the renal endpoint. Kaplan–Meier analyses revealed that both medullary fibrosis and cast formation, but not medullary inflammatory infiltration, were significantly associated with adverse renal outcomes, similarly to the IFTA score. Multivariate Cox regression analysis revealed that medullary fibrosis (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.20–2.16) and cast formation (HR 1.79; 95% CI 1.30–2.45) were independently associated with renal prognosis after adjustment for known risk factors including age, urinary protein and eGFR. Notably, cast formation retained statistical significance even after additional adjustment for the IFTA score (HR 1.53; 95% CI 1.08–2.16). Furthermore, the inclusion of cast formation to a model containing known progression indicators significantly improved the prediction accuracy of renal prognosis (Harrell's C-index: +0.016, p< 0.05). Conclusion: Incorporating medullary findings, particularly fibrosis and cast formation, into renal biopsy assessment may enhance the prediction of renal outcomes beyond conventional cortical pathology findings.