Kidney Adverse Events Associated with Immune Checkpoint Inhibitor Therapy: A Systematic Review and Bayesian Network Meta-Analysis

BACKGROUND: The blockade of immune regulatory sites, cytotoxic T-lymphocyte antigen 4, programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) with immune checkpoint inhibitors has revolutionized survival outcomes in patients with cancer. However, immune checkpoint inhibitors are associated with a range of immune-related adverse events. The aim of this network meta-analysis was to evaluate severe adverse kidney events in patients with oncological or hematological malignancy receiving monotherapy, dual therapy, or combined therapy treatment with immune checkpoint inhibitors when compared with either placebo or standard chemotherapy. METHODS: Phase 3 randomized control trials reporting severe grade (3-5) adverse kidney events were identified across five electronic databases from inception to May 2022. This was supplemented with hand searching of medical journals and the National Clinical Trials registry. A Bayesian network meta-analysis was performed for AKI, hypertension, CKD, and the composite of all acute kidney adverse events. The results are reported as per the PRISMA guidelines. RESULTS: Ninety-five randomized control trials reported severe grade adverse kidney events. The risk of developing severe AKI is higher among patients who received PD-1 plus chemotherapy (odds ratio [OR], 1.8; 95% credible interval [CrI], 1.4 to 2.5) and PD-L1 plus chemotherapy (OR, 1.8; 95% CrI, 1.2 to 2.7) compared with standard chemotherapy and placebo (94 studies, 63,357 participants). The risk of developing the composite of all severe acute kidney adverse events is higher among patients who received PD-1 plus chemotherapy (OR, 1.6; 95% CrI, 1.1 to 2.3) and PD-L1 plus chemotherapy (OR, 1.7; 95% CrI, 1.1 to 2.8) when compared with standard chemotherapy and placebo (95 studies, 63,973 participants). CONCLUSIONS: The combined regimen of PD-1 plus chemotherapy and PD-L1 plus chemotherapy was associated with higher incidence of severe AKI and the composite of all severe acute kidney adverse events. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_07_10_CJN0000000000000160.mp3.