Abstract: FR-PO1268
An Uncategorized Monoclonal Light-Chain-Restricted Pathologic Process
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Rowe, Heather, UPMC, Pittsburgh, Pennsylvania, United States
- Stephenoff, Kevin Michael, UPMC, Pittsburgh, Pennsylvania, United States
Introduction
Monoclonal gammopathy of renal significance (MGRS) occurs when non-cancerous clonal B-cells or plasma cells produce nephrotoxic monoclonal immunoglobulins (Ig) that deposit in the kidney causing damage. Clinical and histological presentation of MGRS vary significantly.
Case Description
37-year-old woman with Crohn's on mercaptopurine presented with chest pain, hypervolemia, hypertensive urgency, proteinuria, and microscopic hematuria. Serum creatinine was 0.7 mg/dL with urine albumin creatinine ratio (UACR) of 2296 mg/g and urine protein creatinine ratio (UPCR) of 3541 mg/g. She had a normocytic anemia. Complements were normal. HIV, hepatitis, and ANCA were negative. ANA was speckled, 1:80 with a negative reflex panel. Serum free light chains were: kappa 51.1 mg/L, lambda 248.3 mg/L (ratio 0.21). Serum protein electrophoresis had a M-spike of 0.3 g/dL with IgG lambda clone. Urine protein electrophoresis detected a lambda monoclonal protein. Kidney biopsy showed diffuse mesangial matrix expansion, segmental mesangial hypercellularity, and Kimmelstiel-Wilson nodules. Kappa and lambda stained 3+ equally. EM with fibrillary deposits in the mesangium without powdery deposits or difference in light chain staining in the glomerular basement membrane. Congo red and DNAJB9 stains were negative. The absence of history of diabetes and high suspicion for paraproteinemia prompted Pronase digestion on paraffin which revealed an IgG lambda restriction on immunofluorescence. Fat pad biopsy was negative for amyloid. Bone marrow showed 15% lambda restricted plasma cell clone. The patient was treated with lenalidomide, bortezomib, dexamethasone, daratumumab induction plus maintenance therapy, and auto stem cell transplant with melphalan. She achieved hematologic remission with improved proteinuria; creatinine 0.8 mg/dL, UACR 462.1 mg/g, UPCR 743.3 mg/g.
Discussion
We present an uncategorized lambda light chain monoclonal restricted process causing MGRS that presented as nodular glomerulosclerosis. Light chain deposition disease is characterized by the accumulation of non-amyloid monoclonal light chains involving the basement membranes throughout the kidney without a fibrillary, crystalline, or microtubular appearance on EM. We emphasize the need for clinicians to have a high index of suspicion for paraproteinemia when nodular glomerulosclerosis is seen on biopsy and suggest Pronase digestion to unmask hidden monoclonal Ig deposits.