Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis

Background: Immune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICIs-based regimens, especially ICIs combination therapy. Methods: We carried out a network meta-analysis of randomized clinical trials (RCTs) to compare the risk of RAEs between ICIs-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types. Findings: 95 RCTs eligible involving 40,552 participants were included. The overall incidence of RAEs, grade 3-5 RAEs, acute kidney injury (AKI) and grade 3-5 AKI was 4.3%, 1.2%, 1.3% and 0.8%, respectively. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR, 0.33; 95％CI, 0.14-0.77), anti-PD-L1 (RR，0.38；95％CI，0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR，0.32；95％CI，0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICIs monotherapy and traditional cancer therapy in terms of RAEs. Anti-CTLA-4 plus anti-PD-1 (RR，1.61；95％CI，1.02-2.56) showed higher risk of RAEs than anti-PD-1. ICIs plus chemotherapy showed increased risk of RAEs and AKI than ICIs monotherapy, chemotherapy and targeted therapy. The results remained robust in meta-regression and sensitivity analyses. Interpretation: Anti-CTLA-4 showed increased toxicity among ICIs monotherapy, especially in terms of grade 3-5 RAEs. Anti-CTLA-4 plus anti-PD-1 showed higher risk of RAEs compared with anti-PD-1. ICIs plus chemotherapy seemed to be the most toxic regimen in terms of RAEs, AKI and grade 3-5 AKI. Registration: The study was registered with PROSPERO, number CRD42020197039. Funding Statement: The project has received funding support from Priority Academic Program Development of Jiangsu Higher Education Institutions, National Natural Science Foundation General Project (81970639), Scientific Research Project of Jiangsu Provincial Health and Wellness Commission (H2017023) and Six Talent Peaks Project in Jiangsu Province (grant no. WSN-056). Declaration of Interests: The authors report no potential conflicts of interest. Ethics Approval Statement: Ethics committee approval was not required for this study design.