Anticancer drug-induced nephrotoxicity: biopsy-proven patterns and outcomes across chemotherapy, targeted therapy, and immune checkpoint inhibitors

Biopsy-confirmed anticancer drug-induced kidney injury is underreported. This study aimed to characterize its clinicopathological features and outcomes. We retrospectively analyzed 52 patients with biopsy-proven anticancer drug-induced nephrotoxicity (2005-2024). Patients were classified into chemotherapy drugs (CTD, <i>n</i> = 25), molecularly targeted therapies (MTT, <i>n</i> = 22), and immune checkpoint inhibitors (ICI, <i>n</i> = 5; PD-1 inhibitors). The CTD group (e.g. cisplatin, capecitabine, gemcitabine) caused frequent acute kidney injury (AKI, 80%), with acute tubulointerstitial nephritis (ATIN, 32%). Notable glomerular lesions in the CTD group included thrombotic microangiopathy (TMA, 12%), minimal change disease (8%), and focal segmental glomerulosclerosis (8%). The MTT group (e.g. bevacizumab, lenvatinib, sorafenib) had higher proteinuria (0.4 <i>vs.</i> 3.1 <i>vs.</i> 0.7 g/24h; <i>p</i> < 0.05) and TMA incidence (86%). MTT-induced TMA produced distinct subtypes: anti-VEGF(R) therapy (<i>n</i> = 11) caused glomerular capillary ballooning (100%); non-VEGFR-TKIs (<i>n</i> = 4) were associated with segmental glomerulopathy; combined anti-VEGF/VEGFR-TKI (<i>n</i> = 4) resulted in more extensive and severe TMA (>75% of glomeruli). ICI therapy (nivolumab, camrelizumab, sintilimab) led to early AKI, mainly ATIN (80%), with glomerular IgA deposition (80%) and low serum C3 (60%). After a median follow-up of 23.0 months, MTT showed faster AKI recovery than CTD (0.5 <i>vs.</i> 8.0 months; <i>p</i> = 0.002). Anticancer drugs induce distinct nephrotoxic patterns. CTD causes direct cytotoxicity and high irreversible injury risk. MTT drives functional TMA, and new-onset hypertension with proteinuria should raise concern for anti-VEGF-related TMA. ICI triggers immune dysregulation with humoral disturbances, and AKI with low serum C3 can be a safety signal for clinical monitoring.