Proliferative glomerulonephritis with monoclonal IgM-kappa deposits responsive to daratumumab therapy—a case report

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare kidney disorder characterized by immune-complex-like glomerular deposits. Its pathogenesis remains unclear, is often linked to monoclonal gammopathy of renal significance (MGRS), but effective treatment strategies are not well established. MGRS refers to kidney injury caused by monoclonal immunoglobulin produced by B-cell or plasma cell clones, without meeting diagnostic criteria for overt multiple myeloma or lymphoproliferative disorders. This case presents a 56-year-old woman who developed a PGNMID-like lesion with monoclonal IgM-kappa deposits along with a more common IgG-dominant pattern. A 56-year-old white woman with a history of progressive renal insufficiency presented with significant fluid retention unresponsive to diuretics, requiring hemodialysis. Urinalysis revealed a urine protein–creatinine ratio of 3136 mg/gCr. A renal biopsy revealed findings suggesting PGNMID. The patient was initially treated with CyBor-D chemotherapy due to suspected clonal plasma cell involvement. Her renal function subsequently improved, allowing the discontinuation of dialysis, though residual symptoms like leg swelling and neuropathy persisted. A hematology consultation during the course prompted the beginning of daratumumab therapy to prevent further renal decline, which was well tolerated, and her renal function remained stable with no worsening of proteinuria or creatinine. PGNMID is often associated with MGUS or lymphoproliferative disorders, though a subset of patients, like ours, lack detectable serum monoclonal proteins. While IgG3 has been implicated in its pathogenesis due to its complement-fixing capacity and self-aggregability, extremely low monoclonal immunoglobulins may still contribute to disease progression. Treatment approaches vary. Immunosuppressive regimens, including rituximab-based therapies, are commonly used. This case presents the potential role of daratumumab in PGNMID treatment, particularly in patients with suspected MGRS-related pathology, suggesting a need for further research into targeted therapies.