Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted molecular therapy with dabrafenib and trametinib: a case report

Background:

Treatment with the combination of molecular targeted therapy, dabrafenib (BRAF inhibitor) plus trametinib (MEK1/MEK2 inhibitor) has been shown to improve progression-free and overall survival in unresectable or metastatic melanoma. Few renal side effects are reported and only case reports exist of interstitial nephritis in relation to this combination therapy.

Case report:

We report a case of a 37-year-old male diagnosed with metastatic melanoma (BRAF V600E mutation) of the scalp (Breslow thickness 3.5 mm, Clark level 3) who developed interstitial nephritis five years into treatment with combination dabrafenib plus trametinib. He had no other significant medical history. In late 2019 he developed a febrile illness with lymphadenopathy and nodal biopsy showed necrotising granulomatous lymphadenitis of unclear aetiology; infective investigations were negative with no evidence of metastatic melanoma. Months later he developed an asymptomatic acute kidney injury (AKI) with a serum creatinine of 174 μmol/L (eGFR 42 mL/min/1.73 m2 ) with an albumin creatinine ratio 8.5 mg/mmol. Kidney biopsy revealed granulomatous interstitial nephritis likely drug related, with three fibrocellular crescents; immunofluorescence was negative and electron microscopy was normal. ANCA and investigations into other causes of AKI were negative, and the biopsy changes were not thought consistent with sarcoidosis. He was treated with prednisolone 1 mg/kg and ceased his targeted therapy with improvement in his renal function and no current evidence of melanoma disease progression.

Conclusion:

Although rare, interstitial nephritis is a serious potential adverse effect of combination dabrafenib plus trametinib therapy. It has now been recognized in a number of case studies including ours and hence our case highlights the importance of increased awareness of this side effect and regular monitoring of renal function in patients on this combination therapy.