Chronic kidney disease (CKD) and renal allograft failure represent escalating global health burdens characterized by progressive tissue remodeling. Although interstitial fibrosis and tubular atrophy (IF/TA) are the primary determinants of long-term prognosis, their assessment currently relies on invasive kidney biopsies, which are unsuitable for longitudinal monitoring. Here, we identify soluble T-cell immunoglobulin and mucin domain-containing protein 3 (sTIM-3) as a robust, non-invasive indicator of renal histopathology and clinical outcomes. In this multi-cohort study, we enrolled 256 kidney transplant recipients (KTRs) with allograft biopsies, 442 native CKD patients with biopsy-confirmed diagnoses, and 44 KTRs with longitudinal follow-up. Pre-biopsy plasma sTIM-3 levels were quantified by ELISA and analyzed for associations with renal function, histopathological parameters, and adverse outcomes. We found that elevated sTIM-3 levels consistently correlated with impaired renal function across diverse etiologies. Notably, post-transplantation sTIM-3 exhibited slower decline kinetics compared to estimated glomerular filtration rate (eGFR), suggesting that it may reflect active tissue remodeling rather than transient functional shifts. Histopathological analyses revealed that sTIM-3 levels increased progressively with IF/TA severity, demonstrating good discriminative capacity for moderate-to-severe fibrosis. Furthermore, in KTRs, elevated sTIM-3 predicted both allograft failure and rapid eGFR decline, with its prognostic value for the latter persisting after adjustment for eGFR and urine protein. Collectively, these findings establish sTIM-3 as a non-invasive biomarker reflecting tubulointerstitial fibrosis and adverse outcomes across diverse kidney disease settings, offering complementary information to conventional functional markers.
Li et al. (2026) studied this question.