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Abstract: SA-PO0182

The Many Faces of Nonclonal Monoclonal Immunoglobulin Deposition Disease: A Case Series

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Yamada, Sofia, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Pasala, Sphoorthy, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Anumolu, Rajesh, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Shah, Sujal I., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Rennke, Helmut G., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Liu, Yuxin, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Chowdhury, Raad Bin Zakir, Brigham and Women's Hospital, Boston, Massachusetts, United States

Group or Team Name

  • Renal Division, Brigham and Women’s Hospital.
Introduction

PGNMID and MIDD are rare monoclonal gammopathies of renal significance (MGRS). PGNMID shows IgG3/kappa deposits with proliferative glomerulonephritis, while MIDD involves kappa light chain and systemic features. Monoclonal protein detection varies (PGNMID ~30%, MIDD ~90%). Nephrotoxic monoclonal immunoglobulins from small B-cell/plasma cell clones drive pathogenesis; PGNMID in children suggests other triggers. We report three cases (2 PGNMID, 1 MIDD) with distinct histological features and outcomes.

Case Description

Three female patients (mean age 55 years, SD 3.61) had median serum creatinine of 3.09 mg/dL (SD 0.673), eGFR of 20.47 mL/min/1.73 m2 (SD 3.97), 24-hour proteinuria of 7,197 mg (SD 4,309), and microscopic hematuria. No clonal populations were detected. Biopsies showed: Patient 1 (PGNMID) showed IgG1/kappa deposits with mesangial IgG1, kappa, C3 positivity, thrombotic microangiopathy (TMA), and was APOL1 positive; Patient 2 (PGNMID) had IgG3/kappa deposits, membranoproliferative injury, fibrocellular crescents; Patient 3 (MIDD) had IgG3/kappa deposits, diffuse proliferative injury, subendothelial/mesangial electron-dense deposits, podocyte damage, and APOL1 positivity. Treatments included Rituximab (n=1), Daratumumab/Bortezomib/Dexamethasone with renal replacement therapy switched to Rituximab (n=1), or conservative management (n=1). Over 8-month follow-up (SD 2), median urine protein-to-creatinine ratio was 5.15 mg/mg (SD 0.382). All patients remain off dialysis; one recovered after brief use, and two maintained stable kidney function.

Discussion

PGNMID and MIDD require kidney biopsy with immunofluorescence and electron microscopy for diagnosis. Despite no clonal detection, high-risk histological features impact prognosis. Clone-directed therapies stabilized renal function, emphasizing early recognition and tailored treatments to prevent ESRD.

Digital Object Identifier (DOI)