A Rare Case of Proliferative Glomerular Nephritis with Monoclonal Immunoglobulin Deposits

Introduction: Monoclonal gammopathies are an important cause of renal deposition diseases, known as monoclonal gammopathy of renal significance (MGRS). MGRS involves non-malignant or premalignant B-cells or plasma cells secreting monoclonal immunoglobulins that damage the kidneys. PGNMID, a new MGRS pathology, affects 1/4 of patients with detectable monoclonal gammopathy and presents with nephrotic syndrome, impaired kidney function, and hematuria. Here, we present a patient with PGNMID and diabetic glomerular sclerosis. Case Description: We present a 78-year-old male with a history of depression, type 2 diabetes, peripheral vascular disease, HTN, HLD, and peripheral neuropathy who presented with abnormal labs: creatinine: 5.27mg/dL (baseline 1.10mg/dL), albumin: 1.1g/dL, and potassium: 5.6mmol/L. He had lower extremity bilateral edema. Urinalysis showed trace ketones, 3+ blood, and 500 protein. A comprehensive workup revealed UPC: 16g, kappa/lambda ratio of 2.04, beta 2 microglobulin level of 16.88 with SPEP beta 2 globulins increased relative to the beta 1 globulins. Renal biopsy indicated PGNMID (IgG3 kappa deposits) with diabetic changes. Hematological workup and bone marrow biopsy confirmed kappa-restricted plasma cell neoplasm. Due to progressive renal failure, he was started on hemodialysis with chemotherapy for continued management of his novel diagnosis. Discussion: PGNMID and MGRS represent significant diagnostic challenges due to their specificity and complexity. Treatment depends on the type of kidney injury, guided by bone marrow biopsy to determine the clonal cell type. Clone-directed therapy could include rituximab, cyclophosphamide, bortezomib, and glucocorticoids. Daratumumab, a monoclonal anti-CD-38 antibody, can also be used if associated with multiple myeloma. If no clone or monoclonal protein is found, conservative therapy with anti-proteinuric agents and blood pressure control is recommended. When common causes like multiple myeloma or lymphoproliferative disorders are excluded, examining the secreted proteins helps distinguish between MGUS and MGRS pathology. Prompt diagnosis with a renal biopsy is essential, followed by a bone marrow biopsy to guide treatment. PGNMID is a rare and complex kidney disease requiring an interdisciplinary treatment approach. Its unique overlap with hematological disorders makes it a compelling subject for ongoing research.