A Woman with Malignant Melanoma Who Developed Membranous Nephropathy After Treatment with a BRAF-MEK Inhibitor

Introduction: Membranous nephropathy (MN) is an immune complex-mediated disease characterized by subepithelial deposits along the glomerular basement membrane (GBM). Typically 70% of primary MN is anti-PLA2-receptor (PLA2R) positive. Secondary MN is often due to infection, drug exposure, and malignancy. We present a case of a young female diagnosed with metastatic melanoma and was found to have MN on kidney biopsy which complicated her treatment. Case Description: 47 year old Caucasian female with history of melanoma and hypothyroidism presented significant compressive right inguinal lymphadenopathy that was consistent with recurrent melanoma. She was initiated on a targeted BRAF/MEK inhibitor. One month later she had worsening bilateral lower extremity edema and new nephrotic range proteinuria (urine protein/creatinine of 5.9 g/g). She was then transitioned to PD-1 immunotherapy, but her malignancy progressed with persistent nephrotic range proteinuria. Five months later she had a 24 hour urine protein of 11.6 g, serum albumin 1.7 g/dL, serum creatinine of 1.0 mg/dL. Renal biopsy showed stage I-II MN with negative NELL1 and PLA2R stains. Due to progression of her disease on PD-1 immunotherapy, she was transitioned back to BRAF-MEK inhibitor therapy and given 2 doses of 1 gram of rituximab for her nephrotic syndrome. Four months later while on BRAF/MEK inhibitor therapy, she did have improvement in her nephrotic syndrome and melanoma markers. Serum albumin improved to 2.2 g/dL.Urine protein/creatinine ratio improved to 3.3 g/g. CD20+ B cells < 1%. One month later, she was hospitalized for complications from malignant pleural effusions and passed away. Discussion: This case highlights the lack of clarity of secondary MN in the oncologic patient and the need to avoid nephro-centric care. Her clinical course was suspicious of BRAF/MEK inhibitor induced secondary MN with nephrotic syndrome. Given the improvement in melanoma and proteinuria with continued therapy it is possible her MN was secondary to her malignancy. It is equally possible that she continued to have MN secondary to her BRAF/MEK inhibitor therapy, which was ameliorated by rituximab. This highlights the importance of focusing on cancer focused therapy for patients with concern for renal manifestations while on targeted chemotherapies.