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Secondary membranous nephropathy can be due to a multitude of causes, but there is an association to malignancy. Membranous nephropathy is classically associated with solid tumors and its presence can affect overall morbidity and mortality. Age and absence of anti-phospholipase A2 receptor appear to be the largest clues to paraneoplastic membranous nephropathy, and presence of thrombospondin 7A and NELL1 are highly linked to paraneoplastic membranous nephropathy. Most troublesome is the patient with no history of malignancy, patients on immunotherapy for their known malignancy, and patients post hematopoietic stem cell transplant as each present a unique set of diagnostic challenges. In the latter two scenarios, membranous nephropathy is a rare but described adverse reaction to immunotherapy, and membranous nephropathy is associated with graft versus host disease after stem cell transplant. In this review we discuss the epidemiology and pathophysiology linking membranous nephropathy to malignancy, challenges in diagnosis and management to include for patients receiving immunotherapy for their malignancy or in remission from their malignancy due to a stem cell transplant, and suggest a clinically relevant approach.
Secondary membranous nephropathy can be due to a multitude of causes, but there is an association to malignancy. Membranous nephropathy is classically associated with solid tumors and its presence can affect overall morbidity and mortality. Age and absence of anti-phospholipase A2 receptor appear to be the largest clues to paraneoplastic membranous nephropathy, and presence of thrombospondin 7A and NELL1 are highly linked to paraneoplastic membranous nephropathy. Most troublesome is the patient with no history of malignancy, patients on immunotherapy for their known malignancy, and patients post hematopoietic stem cell transplant as each present a unique set of diagnostic challenges. In the latter two scenarios, membranous nephropathy is a rare but described adverse reaction to immunotherapy, and membranous nephropathy is associated with graft versus host disease after stem cell transplant. In this review we discuss the epidemiology and pathophysiology linking membranous nephropathy to malignancy, challenges in diagnosis and management to include for patients receiving immunotherapy for their malignancy or in remission from their malignancy due to a stem cell transplant, and suggest a clinically relevant approach.
Membranous glomerulonephritis (MGN) is a rare extra-hematological autoimmune complication of chronic lymphocytic leukemia (CLL), clinically characterized by nephrotic-range proteinuria and, less frequently, renal failure. Because of the rarity of this condition, there is no standardized treatment. Chlorambucil and fludarabine-based regimens, possibly combined with rituximab, have been historically the most frequent therapeutic approaches, with renal response obtained in about two-third of the patients. However, responses are often transient and partial. Here we describe the first patient with rituximab-refractory, CLL-related MGN successfully treated with the Bcl-2 antagonist venetoclax. Nephrotic syndrome resolved as soon as three months after venetoclax initiation, with no unexpected toxicities. At the last follow-up, 17 months after venetoclax start, renal response persists, with proteinuria below 0.5 g/24 hours. This case suggests that targeted agents, particularly Bcl-2 antagonists, might be suitable options for patients with renal autoimmune disorders arising in the context of CLL.
In addition to kidney diseases characterized by the precipitation and deposition of overproduced monoclonal immunoglobulin and kidney damage due to chemotherapy agents, a broad spectrum of renal lesions may be found in patients with hematologic malignancies. Glomerular diseases, in the form of paraneoplastic glomerulopathies and acute kidney injury with various degrees of proteinuria due to specific lymphomatous interstitial and/or glomerular infiltration, are two major renal complications observed in the lymphoid disorder setting. However, other hematologic neoplasms, including chronic lymphocytic leukemia, thymoma, myeloproliferative disorders, Castleman disease and hemophagocytic syndrome, have also been associated with the development of kidney lesions. These renal disorders require prompt recognition by the clinician, due to the need to implement specific treatment, depending on the chemotherapy regimen, to decrease the risk of subsequent chronic kidney disease. In the context of renal disease related to hematologic malignancies, renal biopsy remains crucial for accurate pathological diagnosis, with the aim of optimizing medical care for these patients. In this review, we provide an update on the epidemiology, clinical presentation, pathophysiological processes and diagnostic strategy for kidney diseases associated with hematologic malignancies outside the spectrum of monoclonal gammopathy of renal significance.
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