Spectrum of Glomerular Pathology in Patients Receiving Immune Checkpoint Inhibitors: A 10-Year, Single-Center Perspective

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by enhancing T-cell responses but may trigger off-target renal injury. While acute interstitial nephritis (AIN) and acute tubular injury (ATI) are well-documented, glomerular lesions are not well characterized. Methods: Data on clinical and biochemical parameters, biopsy indications, and histopathologic findings of patients receiving ICI therapy who underwent native kidney biopsies between January 1, 2014, and May 1, 2025 were retrieved and analyzed. Results: Of 211 biopsies, 28 (13%) revealed glomerular pathology. Thrombotic microangiopathy (TMA) was the most common lesion (54%). All 15 TMA cases had concurrent or recent exposure to TMA-associated agents (e.g., VEGF inhibitors, gemcitabine, tyrosine kinase inhibitors), suggesting multifactorial risk. The remaining 13 cases demonstrated heterogeneous non-TMA glomerular lesions: IgA nephropathy (n=6, including one crescentic), secondary FSGS (n=1), membranous nephropathy (n=1), cryoglobulinemic GN (n=1), proliferative GN with monoclonal immune deposits (PGNMID; n=1), pauci-immune crescentic GN (n=1), and diabetic nodular sclerosis (n=2). Median time from ICI initiation to biopsy was 4 months (range 1–20). Biopsies were prompted by AKI (8/13), proteinuria/nephrotic syndrome (4/13), or hematuria (1/13). AIN coexisted in 3 cases. Seven patients received immunosuppressive therapy (5 corticosteroids, 3 rituximab). Four were re-challenged with ICI; two had recurrence. Outcomes varied: 5 achieved remission, 6 died (4 transitioned to hospice), and 2 had limited follow-up. Conclusion: AIN and ATI remain the predominant ICI-associated renal lesions, but glomerular pathologies—though less frequent—are diverse and clinically significant. TMA was always associated with concurrent TMA-inducing agents in our cohort. Kidney biopsy remains essential to define the etiology of renal injury, particularly in complex cases. Importantly, in patients with pre-existing CKD, identifying the underlying kidney pathology prior to ICI initiation may help interpret subsequent renal effects and guide therapeutic approaches.