Abstract: FR-PO1286
The Silent Clone Wars: Monoclonal Gammopathy of Renal Significance and Clone-Directed Therapy
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
- Elattma, Ahmed, Alameda Health System, Oakland, California, United States
- Manjunath, Veena, Alameda Health System, Oakland, California, United States
Introduction
Monoclonal gammopathy of renal significance (MGRS) is a group of kidney disorders caused by deposition of monoclonal immunoglobulins produced by B-cell or plasma cell clones. Despite low tumor burden, the secreted paraprotein may cause severe kidney injury. MGRS is challenging to treat given the disconnect between the silent clone and the aggressive renal damage. Current hematologic guidelines do not recommend treatment for low-burden clonal populations, which risks irreversible kidney damage. We present a case of MGRS manifesting as progressive acute kidney injury with nephrotic-range proteinuria secondary to type I cryoglobulinemic glomerulonephritis, successfully treated with clone-directed therapy.
Case Description
A 43-year-old male without known history presented with headache, diffuse anasarca, and was acutely hypertensive. Laboratory results showed serum creatinine of 1.9 mg/dL, albumin of 2.2 mg/dL, urine protein/creatinine ratio of 19 g/g, and Kappa: Lambda ratio of 9.70. Kidney biopsy showed type I cryoglobulinemic glomerulonephritis with kappa light chain deposition. Bone marrow biopsy identified kappa-restricted plasma cell population of 1.0%. Given the severity of kidney injury, clone-directed therapy with regimen of bortezomib, daratumumab, cyclophosphamide, and dexamethasone was started. The patient had excellent clinical response, achieving kidney recovery with normalization of serum creatinine and resolution of proteinuria.
Discussion
This case highlights the importance of early recognition of MGRS as a unique disease group in which treatment and management must be driven by kidney disease severity rather than clonal burden. Current hematologic treatment thresholds underestimate the urgency of intervention in patients with MGRS. This threshold creates a therapeutic gap because patients with MGRS have sufficient paraprotein to cause devastating kidney injury but do not qualify for standard treatment. Clone-directed therapy should be guided by severity of organ damage rather than clonal burden to avoid irreversible kidney injury. MGRS should be suspected in patients with kidney dysfunction, proteinuria, and monoclonal gammopathy. Early kidney biopsy is critical for diagnosis and guiding clone-directed therapy. Modern regimens present a promising therapeutic strategy in MGRS-associated cryoglobulinemic glomerulonephritis.