Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma: A case report

• Published in: Medicine (Baltimore) Vol. 96; no. 25; p. e7196
• Main Authors: Maanaoui, Mehdi, Saint-Jacques, Camille, Gnemmi, Viviane, Frimat, Marie, Lionet, Arnaud, Hazzan, Marc, Noël, Christian, Provot, François
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 01.06.2017
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzimidazoles - adverse effects; Benzimidazoles - therapeutic use; Carbamates - adverse effects; Carbamates - therapeutic use; Clinical Case Report; Female; Glomerulonephritis - blood; Glomerulonephritis - chemically induced; Glomerulonephritis - pathology; Humans; Kidney - blood supply; Kidney - drug effects; Kidney - pathology; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; MAP Kinase Kinase Kinases - antagonists & inhibitors; Melanoma - blood; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Vasculitis - blood; Vasculitis - chemically induced; Vasculitis - pathology
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000007196

BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors. The patient was a 55-year old woman, who presented a melanoma of the right thigh with pulmonary metastasis. Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively. Two months after the beginning of the treatment, there was a worsening of her renal function with significant proteinuria. Kidney biopsy showed extracapillary proliferation in the glomeruli with a granulomatous reaction. Renal function recovered completely after withdrawal of the chemotherapy. All the reported kidney adverse events secondary to BRAF and MEK inhibitors in the literature are related to the use of BRAF inhibitors. Some previous reported mechanistic investigations also provide insight between BRAF inhibitors and podocytes injuries. Therefore, encorafenib most likely is the main responsible of the disease. However, evidence has emerged that inhibition of the MAP kinase pathway could also enhance autoimmunity. Thus, binimetinib may also have played a role and the combination of BRAF and MEK inhibitors may have facilitated this autoimmune kidney disease.