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Introduction. Monoclonal gammopathy of renal significance (MGRS) is a rare entity describing patients with renal impairment related to the secretion of immunoglobulins without hematological criteria for treatment of a specific disease. We present 3 cases of MGRS identified at our center that were either rare or difficult to diagnose. Case Presentations. The first patient presented with monoclonal membranoproliferative glomerulonephritis in the context of known chronic lymphocytic leukemia (CLL), diagnosed about 10 years prior. She presented with nephritic syndrome with serum protein electrophoresis revealing an IgG/lambda peak of less than 1 g/L, stable from the last few years. A renal biopsy confirmed a diagnosis of monoclonal membranoproliferative glomerulonephritis with granular IgG and C3 deposits of various sizes. The second patient presented with renal TMA in the context of IgM MGUS. The patient was admitted for acute nephritic syndrome and thrombotic microangiopathy. Serum protein electrophoresis demonstrated IgM/kappa paraprotein at 1.8 g/L, with a kappa/lambda ratio of 5.48. Renal biopsy demonstrated endocapillary proliferative glomerulonephritis associated with the presence of numerous monotypic IgM/kappa intracapillary pseudothrombi. Characteristic changes of thrombotic microangiopathy were also described. The third patient presented with immunotactoid glomerulonephritis likely from small B‐cell lymphoma that later transformed to DLBCL. The patient presented with acute renal failure with IgM/kappa paraprotein of less than 1 g/L on electrophoresis and with a kappa/lambda ratio of 7.09. A diagnosis of immunotactoid glomerulonephritis was made on renal biopsy. Bone marrow with limited specimen revealed a B‐cell infiltrate. Biopsy of a breast lesion was compatible with diffuse large B‐cell lymphoma (DLBCL). Lymphomatous cells expressed IgM/kappa, thus confirming paraprotein‐associated renal lesion. Conclusion. We described 3 different cases of MGRS, highlighting the diversity of renal pathohistological presentations and different associated lymphoproliferative disorders. Biopsy should rapidly be considered, as early diagnosis of MGRS is essential to initiate clone‐directed therapy promptly to prevent progression to ESRD or hematologic progression to malignancy.
Introduction. Monoclonal gammopathy of renal significance (MGRS) is a rare entity describing patients with renal impairment related to the secretion of immunoglobulins without hematological criteria for treatment of a specific disease. We present 3 cases of MGRS identified at our center that were either rare or difficult to diagnose. Case Presentations. The first patient presented with monoclonal membranoproliferative glomerulonephritis in the context of known chronic lymphocytic leukemia (CLL), diagnosed about 10 years prior. She presented with nephritic syndrome with serum protein electrophoresis revealing an IgG/lambda peak of less than 1 g/L, stable from the last few years. A renal biopsy confirmed a diagnosis of monoclonal membranoproliferative glomerulonephritis with granular IgG and C3 deposits of various sizes. The second patient presented with renal TMA in the context of IgM MGUS. The patient was admitted for acute nephritic syndrome and thrombotic microangiopathy. Serum protein electrophoresis demonstrated IgM/kappa paraprotein at 1.8 g/L, with a kappa/lambda ratio of 5.48. Renal biopsy demonstrated endocapillary proliferative glomerulonephritis associated with the presence of numerous monotypic IgM/kappa intracapillary pseudothrombi. Characteristic changes of thrombotic microangiopathy were also described. The third patient presented with immunotactoid glomerulonephritis likely from small B‐cell lymphoma that later transformed to DLBCL. The patient presented with acute renal failure with IgM/kappa paraprotein of less than 1 g/L on electrophoresis and with a kappa/lambda ratio of 7.09. A diagnosis of immunotactoid glomerulonephritis was made on renal biopsy. Bone marrow with limited specimen revealed a B‐cell infiltrate. Biopsy of a breast lesion was compatible with diffuse large B‐cell lymphoma (DLBCL). Lymphomatous cells expressed IgM/kappa, thus confirming paraprotein‐associated renal lesion. Conclusion. We described 3 different cases of MGRS, highlighting the diversity of renal pathohistological presentations and different associated lymphoproliferative disorders. Biopsy should rapidly be considered, as early diagnosis of MGRS is essential to initiate clone‐directed therapy promptly to prevent progression to ESRD or hematologic progression to malignancy.
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.
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