Immune Checkpoint Inhibitor-Associated Immune-Mediated Nephropathy: A Real-World Pharmacovigilance Study

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, providing substantial survival benefits across a wide range of malignancies. However, ICI-associated renal toxicity encompasses a broad spectrum of clinical entities, ranging from nonspecific acute kidney injury to well-defined immune-mediated nephropathies with distinct pathophysiological mechanisms. Methods: We performed a large-scale pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate immune-mediated nephropathy associated with ICIs from January 2014 to March 2025. To improve specificity and minimize misclassification, the analysis was restricted to well-defined immune-mediated renal adverse events identified using MedDRA Preferred Terms, excluding nonspecific acute kidney injury. Disproportionality analysis was conducted using reporting odds ratios (RORs) with 95% confidence intervals (CIs) to assess associations between individual ICIs, treatment regimens, and nephropathy reporting. Results: Among 203,652 ICI-related adverse event reports (irAEs), 2361 (1.12%) involved immune-mediated nephropathy. Compared with other irAEs (non-nephropathy), immune-mediated nephropathy was more frequently reported in patients aged ≥ 65 years and in those with lung and genitourinary malignancies. Tubulointerstitial nephritis was the predominant subtype. Higher reporting signals were observed with cemiplimab and pembrolizumab, whereas durvalumab and atezolizumab demonstrated lower reporting signals. Combination regimens involving PD-1 and CTLA-4 inhibitors were associated with higher reporting frequencies compared with monotherapy. Conclusions: This real-world pharmacovigilance analysis identifies clinically relevant differences in immune-mediated nephropathy reporting across ICI classes and treatment strategies. PD-1 inhibitors and PD-1/CTLA-4 combination regimens were associated with higher reporting signals, suggesting potential variation in renal safety profiles. These findings should be interpreted cautiously, given the inherent limitations of spontaneous reporting systems, but they provide hypothesis-generating evidence to support future prospective studies with detailed clinical and histopathological correlation.