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Kidney Week

Abstract: PO2169

Dabrafenib-Induced Acute Interstitial Nephritis (AIN) and AKI in Patients with Cancer

Session Information

  • Onco-Nephrology - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Lee, Meghan, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Seethapathy, Harish Shanthanu, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Efe, Orhan, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Strohbehn, Ian Austin, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Rusibamayila, Nifasha, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Rosales, Ivy, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Colvin, Robert B., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Chute, Donald F., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) commonly used to treat BRAFV600 mutant cancers have been associated with AKI. Cases of acute and chronic tubular injury and AIN have been reported with dabrafenib. We aimed to define the incidence and clinical features of AKI in patients on dabrafenib.

Methods

We conducted a retrospective cohort of patients receiving dabrafenib from 2010-2018 in a large healthcare system. Baseline comorbidities and medication use was determined by chart review. The primary outcome was AKI (≥1.5-fold-increase in baseline creatinine) within 12 months. AKI etiology was reviewed by 2 nephrologists. Multivariable modeling was used to determine predictors of AKI.

Results

Overall, 199 patients were included; mean age was 59 (SD 16) years, 56% were male, and 94% were white. 96% received trametinib (a MEK inhibitor) concurrently. Mean baseline creatinine was 0.9 (SD 0.2) mg/dL, 20 (10%) had baseline CKD (eGFR<60 mL/min/1.73m2), and 42 patients (21%) experienced AKI at a mean of 141 (SD 116) days after starting dabrafenib. In multivariable modeling, only baseline liver disease predicted AKI. Etiology and stage of AKI are shown in Fig 1A; clear alternative causes for AKI were found in 32 of 42 cases. Ten patients (5% of total cohort, 24% of AKI) experienced AKI attributed to dabrafenib-induced cytokine release syndrome (CRS); all experienced fever, chills, gastrointestinal distress (nausea/vomiting/diarrhea) +/- rash and transaminitis within 4-6 weeks of starting dabrafenib. The majority improved with intravenous hydration and discontinuation of the drug. One patient with persistent AKI underwent kidney biopsy demonstrating granulomatous AIN (Fig 1B); he was treated with intravenous solumedrol and a prednisone taper for two weeks with full resolution of AKI.

Conclusion

AKI is common in patients on Dabrafenib (21%). A febrile systemic response or CRS after dabrafenib may explain up to 24% of AKI; we report another case of AIN after dabrafenib.

Funding

  • NIDDK Support