Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

Ying Xiong; Qinxuan Wang; Yangyi Liu; Jingwen Wei; Xiaolei Chen

doi:10.3389/fphar.2022.1023660

Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

Front Pharmacol. 2022 Nov 3:13:1023660. doi: 10.3389/fphar.2022.1023660. eCollection 2022.

Authors

Ying Xiong^{1

2}, Qinxuan Wang³, Yangyi Liu³, Jingwen Wei³, Xiaolei Chen⁴

Affiliations

¹ Department of Periodical Press, West China Hospital, Sichuan University, Chengdu, China.
² Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
³ West China School of Medicine, Sichuan University, Chengdu, China.
⁴ Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Objectives: Tumours remain a serious threat to human life. Following rapid progress in oncology research, tyrosine kinase inhibitors have been used to treat multiple tumour types. Given the great influence of kidneys on pharmacokinetics, renal toxicities associated with TKIs have attracted attention. However, the TKIs with the lowest risks of renal impairment are unclear. In this study, we conducted a Bayesian network meta-analysis to compare the incidence of renal impairment among different TKIs in patients with tumours. Methods and analysis: Six databases (PubMed, EMBASE, The Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database) were electronically searched from inception to 1 November 2021 to identify randomized controlled trials on the incidence of renal impairment for different TKIs in patients with tumours. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Then, a pairwise meta-analysis was conducted using Stata version 13, and network meta-analysis within the Bayesian framework was conducted using R software version 3.5.3 with the package "gemtc 0.8-2" recalling JAGS (version 4.3.0). Results: Overall, 34 randomized controlled trials were included in this study. Although renal toxicity was common among patients receiving TKIs, the incidence and severity greatly differed among the drugs and studies. Elevated creatinine and protein levels were the most common nephrotoxic events, whereas haematuria was relatively rare. Among TKIs, nintedanib and ripretinib carried the lowest risks of renal impairment. Conclusion: TKIs displayed different profiles of renal toxicity because of their different targets and underlying mechanisms. Clinicians should be aware of the risks of renal impairment to select the optimal treatment and improve patient adherence to treatment. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022295853].

Keywords: Bayesian network meta-analysis; renal adverse reactions; treatment; tumours; tyrosine kinase inhibitors.

Publication types

Systematic Review