Case Report: Diagnostic uncertainty in IC-MPGN coexisting with IgM-κ MGUS

Distinguishing immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) with coincident monoclonal gammopathy of undetermined significance (MGUS) from monoclonal gammopathy of renal significance (MGRS) remains challenging when biopsy sampling is inadequate and gold-standard pathologic workup is incomplete.

A 60-year-old woman presented with upper abdominal fullness and heartburn. Routine testing revealed nephrotic-range proteinuria, acute kidney injury (AKI), and hypocomplementemia. Serum immunofixation showed IgM-κ monoclonal gammopathy. Bone marrow examination identified a clonal B-lymphocyte population of approximately 1% with no evidence of lymphoplasmacytic lymphoma or multiple myeloma. Kidney biopsy demonstrated IC-MPGN type I with mesangial and subendothelial electron-dense deposits. Immunofluorescence revealed granular deposition of IgG, IgM, C3, kappa, and lambda, indicating a polyclonal immune complex pattern. Cryoglobulin testing was negative on three occasions under strict 37 °C conditions. These findings suggested but could not confirm IC-MPGN with coincident IgM-κ MGUS; MGRS could not be excluded because only one non-sclerotic glomerulus was available for light microscopy and pronase-digested paraffin immunofluorescence was not performed. The patient received methylprednisolone pulse therapy followed by rituximab. At 1-month follow-up, serum albumin increased from 25.6 to 31.3 g/L, serum creatinine decreased from a peak of 231.0 to 94.0 μmol/L, and 24-h urine protein decreased from 7,930 mg to 1.1 g. Complement C3 and C4 normalized. Clinical improvement was observed following combined therapy; however, the independent contribution of rituximab cannot be determined from this single case.

This case underscores the diagnostic uncertainty inherent in distinguishing coincident MGUS from MGRS when polyclonal immunofluorescence coexists with monoclonal gammopathy but gold-standard pathologic workup is incomplete. It highlights the need for standardized pathologic evaluation, including pronase-digested paraffin immunofluorescence, and illustrates that routine urinalysis in older adults with non-renal symptoms can reveal clinically significant kidney disease.