Dear Editor,

We were interested to read the impressive study by Tan et al. in World Journal of Urology [1] and would like to congratulate the authors for their interesting findings. Tan et al. systematically analyzed the nephrotoxicity between immune checkpoint inhibitor (ICI) combination therapy and sunitinib monotherapy in advanced renal cell carcinoma (RCC) through a meta-analysis based on 7 randomized controlled trials and 5239 patients. The authors identified ICI combination therapy didn’t increase the creatinine, while ICI combination therapy was associated with 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) than sunitinib monotherapy. This research provides valuable insights into clinical management of advanced RCC. However, we wish to discuss the following concerns.

First, the authors limited their literature search to Embase, PubMed, and Cochrane Library [1]. However, they did not explore other international databases with broad subject areas, including ClinicalTrials.gov and Web of Science databases. Selection of a restricted subset of databases for conducting the literature search can lead to biased results, even incorrect conclusions [2].

Second, according to the latest Cochrane Handbook for Systematic Reviews of Interventions 6.3 [2], a high inter-study heterogeneity makes definitive conclusions hard to draw. Although authors attributed the source of heterogeneity to different combination regimens and performed subgroup analyses based on PD-1/PD-L1/CTLA-4 inhibitors, these did not guarantee that the stability of results. Compared with the random effects model used in the article [1], a model called inverse variance heterogeneity (IVhet) could be used as an improved alternative to the random effects model [3]. The known issues of underestimation of the statistical error and spuriously overconfident estimates with the random effects model could be resolved by the use of an estimator under the fixed effect model assumption with a quasi-likelihood based variance structure [3]. Therefore, IVhet model was recommend to be used in future meta-analysis to better evaluate nephrotoxicity between different treatment methods for advanced RCC.

Third, since the recent studies [4, 5] highlighted the importance of health-related quality of life in advanced RCC patients, future studies should further explore the health-related quality of life between patients receiving ICI combination therapy and sunitinib monotherapy.

Finally, we truly thank authors for the excellent and important work.