Abstract: FR-PO1244
Monoclonal Protein, Nonmonoclonal Mechanism: A Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, and Skin Changes (POEMS) Syndrome Diagnosis
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
- Savani, Krupa Hareshkumar, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Ovincy, Cene, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Amin, Md Shahrier, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Parrondo, Ricardo D., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Manohar, Sandhya, Mayo Clinic in Florida, Jacksonville, Florida, United States
Introduction
The Onconephrology differential for monoclonal gammopathy-associated kidney disease is traditionally anchored on deposit-mediated injury (MGRS). However, plasma cell clones can injure the kidney through non-immunoglobulin, indirect mechanisms. POEMS syndrome exemplifies this paradigm: a low-burden lambda-restricted clone is associated with VEGF-mediated endothelial injury without immunoglobulin deposition. We describe a case in which this distinction reframed both diagnosis and management.
Case Description
A 63-year-old man presented with two years of progressive proteinuria (1,071→2,208 mg/24h over 3 months) refractory to antihypertensive optimization, alongside two years of progressive paresthesia, 25-lb weight loss, and an IgA-lambda MGUS (10% lambda-restricted plasma cells on marrow; amyloid and myeloma excluded). EMG confirmed axonal sensorimotor polyneuropathy. Kidney biopsy revealed an MPGN pattern with TMA—endocapillary hypercellularity, capillary-loop occlusion, endothelial swelling, and extensive double contours—without immune deposits or light-chain restriction. Secondary TMA workup was negative, initially raising concern for MGRS-associated TMA. Extra-renal reassessment identified cherry angiomas, asymptomatic papilledema, thrombocytosis (521×10*9/L), and elevated VEGF (252 pg/mL). The patient met both mandatory Dispenzieri criteria, one additional major criterion, and three minor criteria for POEMS syndrome. Clone-directed therapy with daratumumab-lenalidomide-dexamethasone was initiated, with planned autologous stem cell transplant.
Discussion
POEMS broadens the onconephrology differential beyond deposit-mediated disease. Although the plasma cell clone remains the therapeutic target, the renal lesion reflects VEGF-driven endothelial injury, mechanistically distinct from MGRS. The upstream trigger remains incompletely understood: POEMS clones are near-universally lambda-restricted with recurrent mutations in IGLV1-44/1-40 germline segments, yet recent single-cell data suggest VEGF is not produced by the clonal plasma cells themselves, implicating an indirect cytokine cascade from non-clonal cells. A TMA pattern on biopsy in a patient with monoclonal gammopathy and polyneuropathy should prompt VEGF testing and evaluation against Dispenzieri criteria. Recognizing clone-driven, non-deposit renal injury is essential as monoclonal protein testing becomes routine in nephrology.