Kidney Week

Abstract: SA-PO0799

Proliferative Glomerulonephritis with Masked IgG-Kappa Deposits: A Case of Monoclonal Gammopathy of Renal Significance with Complete Response to Clone-Directed Therapy

Session Information

• Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Sharma, Abhinav, Mayo Clinic in Florida, Jacksonville, Florida, United States

Abhinav Sharma, MBBS

• Batish, Ishaan, Mayo Clinic in Florida, Jacksonville, Florida, United States

Ishaan Batish, MBBS

• Fatfat, Adnan, Mayo Clinic in Florida, Jacksonville, Florida, United States

Adnan Fatfat, MD

• Amin, Md. Shahrier, Mayo Clinic in Florida, Jacksonville, Florida, United States

Md. Shahrier Amin, MBBS, PhD, FASN

• Aslam, Nabeel, Mayo Clinic in Florida, Jacksonville, Florida, United States

Nabeel Aslam, MD, FASN

• Jaikishen, Ashwin P., LCMC Health, New Orleans, Louisiana, United States

Ashwin P. Jaikishen, MD

• Bobart, Shane A., Mayo Clinic in Florida, Jacksonville, Florida, United States

Shane A. Bobart, MD, FASN

Introduction

Monoclonal gammopathy of renal significance (MGRS) includes kidney lesions caused by nephrotoxic monoclonal immunoglobulins from a clonal B-cell or plasma cell population without overt hematologic malignancy. Diagnosis is challenging when deposits are “masked” and missed by routine frozen-tissue immunofluorescence. Paraffin immunofluorescence with protease digestion can reveal these deposits. Early recognition is critical because clone-directed therapy may prevent progression and induce renal remission.

Case Description

We present a 62-year-old female with hypertension, peripheral neuropathy, and thromboembolic disease who developed progressive proteinuria and intermittent hematuria over 1 year. Urine protein-to-creatinine ratio (UPCR) rose from 0.4 g/g to 8.5 g/g, with serum creatinine 0.98 mg/dL and eGFR 65 ml/min/1.73 m². Serologic workup showed a small IgG kappa monoclonal protein, prompting kidney biopsy. Pathology showed proliferative glomerulonephritis with negative routine immunofluorescence. Repeat immunofluorescence on paraffin-embedded tissue after protease digestion revealed IgG (2+), IgM (1+), and kappa (2+) dominant deposits with minimal lambda staining, consistent with masked monoclonal deposits. Electron microscopy showed mesangial and rare capillary loop deposits with segmental foot process effacement; Congo red was negative. Bone marrow biopsy showed ~8% clonal plasma cells, confirming monoclonal gammopathy of renal significance. Clone-directed therapy with daratumumab, lenalidomide, and dexamethasone (Dara-Rd) was initiated. The patient achieved a significant renal and hematologic response. Following completion of therapy 6 months later, proteinuria improved from nephrotic range (~8.5 g/g) to 0.084 g/g, accompanied by normalization of the free light chain ratio and improved kidney function ()SCr 0.69 mg/dL, eGFR 97 ml/min/1.73 m²).

Discussion

This case highlights proliferative glomerulonephritis with masked IgG-kappa deposits as a presentation of MGRS. Negative routine immunofluorescence does not exclude monoclonal deposition when clinical features suggest a monoclonal process. Paraffin immunofluorescence with protease digestion should be considered in unexplained proteinuria, hematuria, and monoclonal gammopathy. Timely clone-directed therapy can produce complete renal and hematologic response without overt multiple myeloma.