Abstract: FR-PO1267
Light- and Heavy-Chain Deposition Disease in a Patient with Concurrent Monoclonal Gammopathy of Significance and Transthyretin Amyloidosis: A Diagnostic Challenge
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
- Xiao, Danny L., Northeast Georgia Health System Inc, Gainesville, Georgia, United States
- Jabaji, Ramez S., Emory University School of Medicine, Atlanta, Georgia, United States
Introduction
The coexistence of MGUS (monoclonal gammopathy of undetermined significance) and ATTRwt amyloidosis (Wild-type transthyretin amyloidosis) is an increasingly recognized clinical scenario. We report a case of Light and Heavy Chain Deposition Disease (LHCDD) presenting with progressive kidney dysfunction in a patient with both MGUS and ATTRwt cardiac amyloidosis, that led to a shift in treatment trajectory.
Case Description
A 72-year-old man without known chronic kidney disease, presented for evaluation of slowly progressive kidney dysfunction. MGUS and cardiac amyloidosis were diagnosed 5 years prior; bone marrow biopsy showed 15% IgG lambda plasma cell dyscrasia and endomyocardial biopsy with Liquid Chromatography-Mass Spectrometry (LC-MS) findings consistent with ATTRwt. Baseline creatinine ranged 0.9-1.2mg/dL, which slowly increased to 2.16-2.6mg/dL. He had overt albuminuria (341mg/g). Serum and urine protein electrophoresis showed 1.5g/dL and 3.7% M-spike with lambda light chain predominance. Two kidney biopsies showed mesangial expansion, positive mesangial and glomerular basement membrane staining for immunoglobulin G and lambda light chains. Staining for kappa and Congo red was negative. Electron microscopy confirmed fine powdery deposits. These findings prompted plasma cell directed therapy with Dara-CyBorD (Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone).
Discussion
Distinguishing amyloidosis subtypes is critical in guiding therapy and prognosis; patients with ATTRwt amyloidosis may be inappropriately subjected to chemotherapy, while patients with AL may receive ineffective ATTR-directed therapy. LC-MS is the gold standard for amyloid fibril typing, with reported specificity of 96%. However, the coexistence of MGUS complicates the diagnostic evaluation. Renal involvement in ATTRwt has been considered rare and is often seen in ATTRv (hereditary form). Conversely, MGUS may transform into MGRS (monoclonal gammopathy of renal significance), which carries an excellent prognosis with early detection and modern daratumumab based regimens that achieve a deep hematologic response.