Pharmacovigilance Study of Drug-Related Renal Vascular Lesions Based on FAERS and Experimental Exploration

Purpose Drug-related renal vascular lesions are an underrecognized cause of severe nephrotoxicity. We aimed to map drug signals for renal vascular injury in FAERS and to provide experimental evidence for plausible vascular mechanisms. Methods We extracted 19,231 FAERS reports (Q1 2004–Q4 2024) and applied four disproportionality algorithms (ROR, PRR, MGPS, BCPNN) plus χ² screening and multivariable logistic regression to prioritize suspect agents. Time-to-onset and reporting characteristics were described. Three high-risk drugs (imatinib, rofecoxib, tenofovir disoproxil) were tested in vitro on HUVECs and HEK293A cells using CCK-8 viability and FITC/PI apoptosis assays; short-term intraperitoneal dosing in mice provided preliminary histologic correlation. Results Nineteen drugs met signal criteria. Time-to-onset analysis revealed a bimodal distribution: an “ultra-acute” cluster (median ≈ 1 day; e.g., CAR-T products, contrast agents) and a delayed cluster (months–years; e.g., rofecoxib, tenofovir). In vitro, all three tested drugs produced concentration- and time-dependent reductions in cell viability and increased apoptotic/necrotic fractions, with endothelial (HUVEC) cells more susceptible than renal epithelial (293A) cells. Short-term murine kidney histology showed small-vessel congestion, focal hemorrhage, and perivascular inflammation after drug exposure. Conclusion Combined pharmacovigilance and experimental data identify candidate drugs associated with renal vascular lesions and provide preliminary mechanistic plausibility for direct endothelial injury. These findings support tailored clinical vigilance and prioritization of mechanistic and prospective validation studies.