Masked IgG-kappa dominant proliferative glomerulonephritis as monoclonal gammopathy of renal significance with marked renal response to daratumumab-based therapy

Monoclonal gammopathy of renal significance (MGRS) encompasses renal lesions caused by nephrotoxic monoclonal immunoglobulins produced by small B-cell or plasma cell clones that do not meet criteria for overt hematologic malignancy. Diagnosis may be challenging when immune deposits are masked on routine immunofluorescence. We report a 63-year-old woman with hypertension, chronic kidney disease, peripheral neuropathy, venous thromboembolism, and progressive proteinuria who underwent kidney biopsy for worsening urinary abnormalities. Routine immunofluorescence on frozen tissue was negative; however, repeat immunofluorescence on protease-digested paraffin-embedded tissue demonstrated focal and segmental granular staining for IgG and kappa light chain with essentially negative lambda staining, consistent with proliferative glomerulonephritis with masked IgG-kappa dominant deposits. Congo red stain was negative. Bone marrow biopsy subsequently showed approximately 8% plasma cells with an abnormal kappa-excess plasma cell population, and serum immunofixation identified IgG-kappa monoclonal protein, supporting MGRS. Due to baseline peripheral neuropathy, bortezomib-based therapy was deferred, and the patient was treated with daratumumab, lenalidomide, and dexamethasone. Kidney function remained preserved, and proteinuria improved markedly from nephrotic-range level of 8.5–0.22 g/g. This case highlights the diagnostic importance of paraffin immunofluorescence when MGRS is suspected despite negative routine studies and illustrates that early clone-directed therapy can produce substantial renal response in masked monoclonal proliferative glomerulonephritis.