Clinical features of acute kidney injury in patients receiving dabrafenib and trametinib

Nephrol Dial Transplant. 2022 Feb 25;37(3):507-514. doi: 10.1093/ndt/gfaa372.

Abstract

Background: Our objective was to characterize the incidence, risk factors and clinical features of acute kidney injury (AKI) in patients receiving dabrafenib and trametinib.

Methods: We performed a retrospective cohort study examining the kidney outcomes of patients in a large healthcare system who received dabrafenib/trametinib between 2010 and 2019. The primary outcome was AKI, defined as a 1.5-fold increase in serum creatinine from baseline within a 12-month study period. AKI severity and etiology was determined for each case by chart review. Logistic regression was used to evaluate baseline predictors of AKI.

Results: A total of 199 patients who received dabrafenib in our healthcare system from 2010 to 2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of the total cohort, 24% of AKI patients) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms and elevated liver enzymes. Preexisting liver disease was the only significant predictor of AKI in the cohort. One patient had biopsy-proven granulomatous acute interstitial nephritis that resolved with corticosteroids.

Conclusions: Oncologists and nephrologists should be aware that AKI is common after dabrafenib/trametinib and a substantial number of cases occur in the setting of treatment-induced pyrexia.

Keywords: BRAF; MEK; acute kidney injury; nephrotoxicity.

Publication types

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

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / epidemiology
  • Antineoplastic Combined Chemotherapy Protocols
  • Humans
  • Imidazoles
  • Melanoma* / drug therapy
  • Melanoma* / etiology
  • Mutation
  • Oximes
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / therapeutic use
  • Pyridones
  • Pyrimidinones
  • Retrospective Studies

Substances

  • Imidazoles
  • Oximes
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Proto-Oncogene Proteins B-raf
  • dabrafenib