Immune-related adverse events and kidney function decline in patients with genitourinary cancers treated with immune checkpoint inhibitors

Eur J Cancer. 2021 Nov;157:50-58. doi: 10.1016/j.ejca.2021.07.031. Epub 2021 Sep 2.

Abstract

Background: In patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown.

Patients and methods: This is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year.

Results: 637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR<60 mL/min/1.73 m2 at baseline. irAEs, AKI, and sustained eGFR loss were common, occurring in 33%, 25% and 16%, respectively. Compared to patients with urothelial carcinoma, patients with RCC were more likely to develop irAEs (aHR 1.61, 95% CI 1.20-2.18) and sustained eGFR loss (aHR 1.97, 95% CI 1.24-3.12), but not AKI (aHR 1.53, 95% CI 0.97-2.41). Among patients surviving ≥1 years, experiencing a non-renal irAE was associated with a significantly higher risk of sustained eGFR loss (aHR 1.71, 95% CI 1.14-2.57).

Conclusion: AKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs.

Keywords: Acute kidney injury; Chronic kidney disease; Immune checkpoint inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / physiopathology
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / physiopathology

Substances

  • Immune Checkpoint Inhibitors