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Kidney Week

Abstract: SA-PO212

Acute Interstitial Nephritis Associated with Dabrafenib-Related Pyrexia: A Case Report

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Ong, Yi-Ting, Singapore General Hospital, Singapore, Singapore
  • Tan, Ya Hwee, National Cancer Centre Singapore, Singapore, Singapore, Singapore
  • Tan, Hui Zhuan, Singapore General Hospital, Singapore, Singapore
Introduction

Acute kidney injury is common in patients receiving proto-oncogene B-Raf (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, with a subset occurring in conjunction with BRAF/MEK-related pyrexia (Seethapathy et al. Nephrol Dial Transplant, 2022). We report a rare case of biopsy-proven acute tubulo-interstitial nephritis (ATIN) diagnosed in the setting of Dabrafenib-related pyrexia.

Case Description

A 69-year-old Chinese female with metastatic melanoma was referred for KDIGO Stage 3, non-oliguric acute kidney injury (AKI) [baseline sCr 54 µmol/L, peak sCr 195 µmol/L], occurring in the setting of Dabrafenib-induced pyrexia. She was reinitiated on Dabrafenib alone at a reduced dose of 75mg 3 weeks prior to presentation, after developing drug-induced liver injury to Dabrafenib/Trametinib (DT). Notably, she last received Nivolumab, an immune checkpoint inhibitor (ICI) 4 months prior, but had no recent exposure to proton pump inhibitors, non-steroidal anti-inflammatory drugs or antibiotics.

Evaluation showed pyuria (urinary WBC 15/µL) and sub-nephrotic range proteinuria (uPCR 1.34g/g). Serum C-reactive protein was elevated at 17.8 mg/L. Autoimmune markers and virologies were negative. AKI was slow to improve despite supportive therapy and fever lysis. Kidney biopsy showed severe ATIN, with a small non-necrotising granuloma. There were no other clinical features suggestive of a systemic sarcoid-like reaction. She was started on prednisolone 60mg (1mg/kg), which was tapered over 7 weeks. Partial renal recovery was observed (sCr 76µmol/L). Dose-reduced DT was resumed 8 weeks later without prophylactic steroids. No recurrence of AKI was observed during 3 months of follow-up.

Discussion

AKI occurring with BRAF/MEK-related pyrexia can result from multiple etiologies. Cytokine release and NSAID use are common causes, but ATIN is an important differential. We postulate that previous ICI exposure could have contributed to the development of ATIN given their potential for longer-term modulation of immune tolerance. Diagnostic kidney biopsy should be strongly considered if AKI persists despite fever lysis and supportive therapy, especially in patients with past ICI exposure. Our case suggests that same-drug rechallenge is feasible, with or without prophylactic steroids, together with close monitoring for AKI recurrence.