Abstract: FR-PO0936
A Rare Convergence: Monoclonal Gammopathy Orchestrating Coexistent C3 Glomerulonephritis and Atypical Hemolytic Uremic Syndrome
Session Information
- Glomerular Case Reports: Lupus, FSGS, Complement, and More
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Sinha Ray, Abhisekh, Creighton University, Omaha, Nebraska, United States
- Errabelli, Praveen K., Allina Health, Minneapolis, Minnesota, United States
- Lathiya, Maulik, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Mareedu, Neeharik, UPMC Western Maryland, Cumberland, Maryland, United States
Introduction
Monoclonal gammopathy of renal significance (MGRS) involves paraprotein-related kidney disease from a B-cell or plasma-cell clone not meeting lymphoma or multiple myeloma criteria. Monoclonal immunoglobulins (Ig) can cause kidney damage directly or by dysregulating the alternative complement pathway, leading to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulonephritis (C3GN)
Case Description
A 48-year-old male with no significant medical history, presented with headache, shortness of breath, oliguria, and leg swellings. He was found to have hypertensive emergency (232/128 mmHg), severe anemia (hemoglobin 5 g/dL), thrombocytopenia (94 K/µL), and acute kidney injury (creatinine 11.5 mg/dL with normal baseline). He required diuretics, IV antihypertensives, transfusions, and ultimately dialysis.
Serologic and infectious workup was negative. Suspecting thrombotic microangiopathy (TMA), plasmapheresis (PLEX) was initiated. A renal biopsy revealed moderate mesangial sclerosis, near global intracapillary thrombi, arteriolar thrombi, severe interstitial fibrosis, and tubular atrophy, with immunofluorescence showing trace IgG and 2+ C3 in the mesangium. ADAMTS13 activity was 67%. A diagnosis of aHUS led to discontinuing PLEX and starting Eculizumab. Electron microscopy also indicated nodular mesangial expansion and large electron-dense deposits, consistent with C3GN, suggesting pre-existing glomerulopathy. Genetic testing for aHUS was negative.
Further investigation showed a monoclonal protein (0.3g/dL) in serum, IgG-Kappa monoclonal protein in urine, a serum Kappa/Lambda ratio of 2.35, and 8% monoclonal plasma cells in the bone marrow, confirming MGRS. The patient received Eculizumab for two years and 6 cycles of CyBorD for MGRS. While hematological parameters normalized, renal function did not improve, and he remained on dialysis.
Discussion
Dysregulation of the complement cascade links C3GN and aHUS, though their coexistence is rare. A French C3GN cohort (278 patients) found only 6% had biopsy-proven TMA, including 4 with MGRS, with a median renal survival of 49 months despite treatment. MGRS-related aHUS patients have higher rates of progression to end-stage renal disease. This patient, with MGRS-related C3GN and aHUS, showed no renal improvement despite treatment with Eculizumab and chemotherapy.