Purpose: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. Methods: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. Results: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77–1.37, P = 0.87) and grade 3–5 (RR = 1.48, 95% CI: 0.19–11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54–3.51, P < 0.0001) and grade 3–5 proteinuria (RR = 2.25, 95% CI: 1.21–4.17, P = 0.01). Conclusions: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic. [ABSTRACT FROM AUTHOR]