Medullary pathological findings provide additional prognostic information beyond cortical pathology in native kidney biopsies

Renal biopsy provides important prognostic information in chronic kidney disease (CKD), primarily based on cortical histopathological lesions such as cortical interstitial fibrosis and tubular atrophy (IFTA). However, the prognostic significance of renal medullary lesions remains unclear. We investigated whether medullary pathological findings are independently associated with renal outcomes and improve prognostic discrimination beyond conventional cortical assessments. In this single-center retrospective cohort study, 488 adult patients with adequate medullary tissue were included among 1,136 native kidney biopsies performed between 2011 and 2023. Medullary fibrosis, inflammatory cell infiltration, and cast formation were semi-quantitatively graded. The primary outcome was a composite of ≥ 40% decline in estimated glomerular filtration rate or initiation of renal replacement therapy. During a median follow-up of 2.3 years, 112 patients (23.0%) reached the composite renal outcome. In multivariable analysis adjusted for age, sex, baseline eGFR, and proteinuria, medullary cast formation were significantly associated with adverse renal outcomes, and the association remained significant after additional adjustment for cortical IFTA. Notably, addition of medullary cast formation significantly improved model fit and prognostic discrimination. These findings suggest that systematic evaluation of medullary lesions may enhance risk stratification in CKD.