Immune Checkpoint Inhibitor-Associated Glomerular Disease: A Systematic Review and Descriptive Analysis

Abstract Background Immune checkpoint inhibitors (ICI) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAE) are now well-recognized, with incidence of 2-5%. The majority of initial data related to kidney IRAE has focused on acute interstitial nephritis (AIN). There is minimal data on the types and relative frequency of glomerular diseases associated with ICI, their treatment, and outcomes. Methods We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICI. We searched the MEDLINE, EMBASE and Cochrane Central databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury. Results After screening, 27 manuscripts with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis and renal vasculitis (27%), podocytopathies (24%), and C3 glomerulonephritis (11%). Concomitant AIN was reported among 41%. The majority of patients had ICI discontinued (88%), and nearly all received corticosteroids (98%). Renal replacement therapy was required in 25%. Most patients had full (31%) or partial (42%) recovery from AKI, although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively. Conclusions Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune glomerulonephritis, podocytopathies and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICI and consider kidney biopsy when features atypical for AIN are present.