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

BACKGROUND: The blockade of immune regulatory sites, CTLA-4, PD-1, and PD-L1 with Immune Checkpoint Inhibitors has revolutionized survival outcomes in cancer patients. However, immune checkpoint inhibitors are associated with a range of immune related adverse events. The aim of this network meta-analysis is 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 to either placebo or standard chemotherapy. METHODS: Phase III 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: acute kidney injury, hypertension, chronic kidney disease and the composite of all acute kidney adverse events. The results are reported as per PRISMA guidelines. RESULTS: 95 randomized control trials reported severe grade adverse kidney events. The risk of developing severe acute kidney injury is higher among patients who received PD-1 plus chemotherapy (OR 1.8 [95% CrI 1.4 to 2.5]) and PD-L1 plus chemotherapy (OR 1.80 [95% CrI 1.2 to 2.7]) compared to 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 to standard chemotherapy and placebo (95 studies, 63, 973 participants). CONCLUSIONS: The combined regimen of PD-1 + chemotherapy and PD-L1 + chemotherapy was associated with higher incidence of severe acute kidney injury and the composite of all severe acute kidney adverse events.