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. 2022 Aug 31;16(5):817-826.
doi: 10.1093/ckj/sfac194. eCollection 2023 May.

The association between acute kidney injury and outcomes in cancer patients receiving immune checkpoint inhibitor therapy: a systematic review and meta-analysis

Mehmet Kanbay  1 , Sidar Copur  2 , Dimitrie Siriopol  3 , Abdullah Burak Yildiz  2 , Metehan Berkkan  2 , Raluca Popa  3 , Nuri Baris Hasbal  1 , Alberto Ortiz  4 , Mark A Perazella  5
Affiliations

The association between acute kidney injury and outcomes in cancer patients receiving immune checkpoint inhibitor therapy: a systematic review and meta-analysis

Mehmet Kanbay et al. Clin Kidney J. .

Abstract

Background: Immune checkpoint inhibitors (ICPIs) are a novel therapeutic approach to cancer treatment that have changed the landscape of cancer therapy but also have some considerable drawbacks. Acute kidney injury (AKI) is one of these potential complications that may have effects on patient outcomes. In this review, we assessed the effect of AKI on mortality outcomes in cancer patients receiving this immunotherapy.

Methods: We performed a systematic review and meta-analysis of prospective, retrospective, randomized and non-randomized studies, which examined the effects of AKI in cancer patients receiving immune checkpoint inhibitors. We searched through PubMed, Medline, Web of Science, Scopus and Cochrane Library databases.

Results: Seven studies were included in the final analysis, with a total number of patients of 761. Overall, the risk of death was higher in patients that developed AKI during ICPI treatment [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.05-1.92, P = 0.02; heterogeneity χ2 = 11.68, I2 = 66%, P = 0.02] compared with patients that did not develop AKI. In addition, there was a trend to a better survival in those with less severe AKI patients compared with those with more severe AKI (HR 1.35, 95% CI 0.99-1.83, P = 0.05). Lastly, it was seen that patients with persistent kidney dysfunction (non-recovery) had an increased risk for all-cause mortality (HR 2.93, 95% CI 1.41-6.08, P = 0.004; heterogeneity χ2 = 0.53, I2 = 0%, P = 0.47).

Conclusions: Development of AKI in patients with cancer receiving immune checkpoint inhibitors is associated with increased risk of mortality.

Keywords: acute kidney injury; acute renal failure; immune checkpoint inhibitors; immunotherapy; nephrotoxicity.

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Conflict of interest statement

M.K. is member of the CKJ editorial board. A.O. is the previous CKJ Editor-in-Chief. The other authors declare that they have no conflict of interest.

Figures

Figure 1:
Figure 1:
Flow diagram of the study selection process.
Figure 2:
Figure 2:
Forest plot of association between outcomes of AKI and non-AKI in patients on ICPI.
Figure 3:
Figure 3:
Forest plot of association between Stage 1, 2 AKI and Stage 3 AKI in patients on ICPI.
Figure 4:
Figure 4:
Forest plot of association between recovery and non-recovery of AKI patients in patients on ICPI.
Figure 5:
Figure 5:
Pathways of AKI development. Blockage of inhibitory pathways allows aberrant T-cell response against self-tissues. Checkpoint blockage also leads to development of autoantibodies and causes damage via several mechanisms. DC, dendritic cells.
See this image and copyright information in PMC

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