A Case of Severe Membranous Nephropathy Complicated by Chylothorax

Introduction: Membranous nephropathy (MN) is one of the most common causes of adult-onset nephrotic syndrome (NS). Development of chylothorax is a very rare complication of MN. We present a patient with severe MN, refractory to two first-line immunosuppressive therapy regimens, who developed a chylous pleural effusion, which eventually resolved after the use of cyclophosphamide-based Ponticelli protocol. Case Description: A 61-year-old White man without any known medical history presented with profound peripheral edema, hypertension, hyperlipidemia, >10 grams per day on 24-hour urine collection, and normal kidney function. Kidney biopsy showed MN with negative PLA2R on tissue staining and serum. A thorough age-appropriate malignancy workup was negative. He was initially treated with rituximab (RTX) infusion 1g x2, followed by initiation of tacrolimus, given minimal response to RTX. He developed progressively worsening shortness of breath, found to have moderate to large right pleural effusion on chest x-ray requiring thoracentesis, with the removal of 1.5L of cloudy white/yellow fluid, with triglyceride (TG) levels of 143 mg/dL. He continued to require monthly thoracentesis. After transitioning to a cyclophosphamide-based regimen with the Ponticelli protocol, he had complete resolution of pleural effusions with partial remission of NS. Discussion: Chylothorax occurs when the thoracic duct or its tributaries are disrupted, leading to chyle leakage and accumulation into the pleural cavity. The pathophysiology of chylothorax in the setting of MN is not well understood. Proposed theories include increased permeability due to hypoproteinemia or increased lymphatic vessel pressure from severe tissue edema. Immune-mediated damage to lymphatic vessels related to the MN disease process is also a possibility. Further research is needed to elucidate the precise mechanisms underlying this association. Our case underscores the challenges in managing MN and highlights a rare complication of this disease.