A Leap Forward: Overcoming Diagnostic Hurdles in Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare disease requiring kidney biopsy for diagnosis and differentiation from other entities causing a membranoproliferative pattern of injury. We report the case of a 20-year-old pregnant patient with an initial biopsy diagnosis of membranoproliferative glomerulonephritis (MPGN) whose worsening renal function prompted a repeat biopsy that revealed PGNMID, underscoring the challenges of accurate diagnosis in the setting of a membranoproliferative pattern of injury. Case Description: A 20-year-old female, G1P0 presented at 18 weeks gestation with hypertension and proteinuria (9.6 g/24 hours). Initial kidney biopsy revealed MPGN with trace C3 and IgM staining on immunofluorescence (IF). She was treated with oral prednisone and lost to follow up. Three years later, she returned with nephrotic syndrome (8.5 g of proteinuria/24 hours, serum albumin 2.1 g/dL) and kidney dysfunction (serum creatinine (sCr) 1.7 mg/dL). Repeat kidney biopsy showed MPGN pattern of injury but with IF positive for kappa restricted IgG and C3. IgG subclass staining showed monotypic IgG3. Bone marrow biopsy and serum/urine protein electrophoresis did not reveal a clonal population. She was ultimately diagnosed with PGNMID and treated with daratumumab, bortezomib, cyclophosphamide and dexamethasone. At 12-month follow up, her edema had resolved with improvement of proteinuria (1.4 g/24 hrs) and kidney function (sCr 1.1 mg/dL) along with normalization of serum albumin (4.0 g/dL). Discussion: The complexity of PGNMID care stems from the frequent absence of a detectable clonal population, the need for additional confirmatory diagnostic maneuvers (immunoglobulin subclass staining or pronase digestion), and the lack of randomized controlled trials to guide management. Biopsy findings can evolve, with monotypia being detected at various points in the clinical course, as seen in our case. However, with recent advancements in understanding of PGNMID, clinicians are increasingly confident using plasma-cell directed therapy, as in our case, where a daratumumab-based regimen resulted in resolution of edema and improvement in proteinuria and kidney function.