Kidney adverse events associated with calcineurin inhibitors: a real-world study based on the FAERS database and network pharmacology

Objective: This study utilized FDA Adverse Event Reporting System (FAERS) data and network pharmacology methods to evaluate the risk of renal adverse events (AEs) associated with calcineurin inhibitors (CNIs), providing guidance for safe drug use. Method: By analyzing FAERS data from 2004 to 2024, we identified renal AEs associated with CNI therapy. We employed imbalance analysis (report odds ratio [ROR], proportion of reports ratio [PRR], MGPS, and Bayesian confidence propagation neural network [BCPNN]) to detect signals and explored drug-gene interaction networks to investigate potential mechanisms. Results: Revealed significant associations between cyclosporine, tacrolimus, and voclosporin with renal injury, with voclosporin showing stronger correlations (ROR = 5.24, PRR = 4.85, EBGM05 = 4.85, IC025 = 2.28) but lower mortality rates. Network pharmacology analysis suggested that cyclosporine, tacrolimus, and everolimus may exert their toxic effects by acting on core genes. Conclusion: The widespread use of CNIs raises concerns about their renal safety. This study provides new evidence from real-world data indicating differences in renal toxicity risk and mechanisms among calcineurin inhibitors (CNIs), underscoring the importance of pharmacovigilance strategies for patients with autoimmune diseases.