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

Objectives 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 199 patients who received dabrafenib in our healthcare system from 2010-2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of total cohort, 24% of AKI) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms, and elevated liver enzymes. Pre-existing 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.