Thrombotic Microangiopathy and Membranous Nephropathy: A Complicated Paraneoplastic Disorder

Introduction: Hematologic malignancies are associated with a myriad of paraneoplastic glomerular pathologies. Various lesions have been described with Mantle cell lymphoma (MCL). We hereby describe a case of concomitant membranous nephropathy (MN) and thrombotic microangiopathy (TMA) in the context of relapsed MCL. Case Description: A 68-year-old male with history of MCL previously in remission presented with generalized edema. MCL had recently relapsed and patient was set to start Zanubrutinib. He had AKI (Creatinine 2 mg/dL, baseline 1.2), hypoalbuminemia (1.8 g/dL), nephrotic range proteinuria (13 g/day), normocytic anemia and mild thrombocytopenia. Complements were depleted with a negative serologic workup including PLA2R and THSD7A. Kidney biopsy showed subacute/chronic TMA along with MN. Tissue PLA2R staining was negative. Pathologies were felt to be paraneoplastic and as such lymphoma directed therapy was intensified. Two months later, worsening AKI and anasarca prompted dialysis initiation. Microangiopathic hemolytic anemia and thrombocytopenia were noted along with depleted haptoglobin. Complements remained depleted with elevated sC5b-9 (>2130ng/ml; ref <244ng/ml). Imaging suggested lack of lymphoma response. Along with changing lymphoma therapy, decision was made to initiate eculizumab. This led to liberalization from dialysis (creatinine nadir 1.9 mg/dL) and stabilization of hematologic parameters. Haptoglobin and sC5b-9 also normalized. Attempt at stopping eculizumab after 8 weeks resulted in worsening of kidney and hematologic parameters. Upon restarting eculizumab, things stabilized again. Four months after resuming therapy, kidney function remains stable with improving proteinuria (creatinine 1.9 mg/dL; albumin 3.8g/dL). MCL remains stable. Discussion: We present a complex paraneoplastic renal pathology of MN and TMA in the context of relapsed MCL. While addressing the underlying malignancy remains the cornerstone of management, given the severity of the presentation eculizumab was successfully used here to stabilize the situation until meaningful hematologic response is achieved. This case highlights that management of these ever-challenging cases needs to be individualized and requires an interdisciplinary approach