A Case of IgM-Type Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits Developing During the Course of Lymphoplasmacytic Lymphoma

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare monoclonal gammopathy of renal significance characterized by glomerular deposition of monoclonal immunoglobulin deposits and light chain. Among its subtypes, IgM-type PGNMID is particularly rare, accounting for approximately 10% of all PGNMID cases and often associated with B-cell lymphoproliferative disorders. We report a case of IgM-type PGNMID associated with lymphoplasmacytic lymphoma (LPL) which progressed and developed nephrotic syndrome despite sustained serologic remission with tirabrutinib, necessitating a repeat kidney biopsy. Case Description: A 72-year-old male patient with a 14-year history of LPL underwent treatment with corticosteroids and rituximab, yet exhibited a suboptimal therapeutic response. Hematologic remission was achieved following the initiation of tirabrutinib three years ago. Nevertheless, an increase in proteinuria (2.0 g/gCr, serum creatinine 0.9 mg/dL) was detected, and then we performed kidney biopsy, which revealed mesangial hypercellularity, double contours of the glomerular basement membrane, and expansion of the subendothelial space with predominant IgM and λ light chain deposition, revealing non-organized electron-dense deposits in the mesangial and subendothelial areas in electron microscopy. These findings led to a diagnosis of IgM-type PGNMID. Despite ongoing hematologic remission with low serum IgM levels and no detectable M-protein, the patient exhibited nephrotic syndrome accompanied by deteriorating kidney function, necessitating a second kidney biopsy. The kidney biopsy indicated a progression of interstitial fibrosis and glomerular sclerosis, with no evidence of de novo glomerulonephritis and improvement of nephritis activity. Discussion: This case demonstrates progressive nephrotic syndrome due to IgM-type PGNMID despite stable disease activity of LPL. This discrepancy may be attributable to a highly pathogenic monoclonal IgM. IgM-type PGNMID is associated with a poor kidney prognosis, with a median kidney survival of 44 months, which is consistent with this case. Retrospectively, despite the achievement of serologic remission, the deterioration in kidney function may have warranted consideration of subsequent treatment strategies, such as the use of proteasome inhibitors or B-cell lymphoma-2 inhibitors.