Abstract: SA-PO0723
MCP/CD46 Allele-Associated Renal-Limited Thrombotic Microangiopathy: A Case Suggestive of Complement-Mediated Disease
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cheng, Derek, Temple University, Philadelphia, Pennsylvania, United States
- Ojeniyi, Solabomi Oyeronke, Temple University, Philadelphia, Pennsylvania, United States
- Hassler, Jared, Temple University, Philadelphia, Pennsylvania, United States
- Gillespie, Avrum, Temple University, Philadelphia, Pennsylvania, United States
Introduction
Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury. However, emerging evidence recognizes renal-limited TMA in which patients lack systemic hematologic manifestations, often within the spectrum of complement-mediated atypical hemolytic uremic syndrome (c-HUS). Advances in genetic testing allow for better characterization of these patients.
Case Description
A 56-year-old woman with thrombocytosis, osteoarthritis, endometriosis, liver steatosis, and positive antinuclear antibody was evaluated for proteinuria. Kidney biopsy revealed TMA with mild interstitial fibrosis and tubular atrophy (20%) and mild arteriosclerosis. Electron microscopy showed approximately 30% podocyte foot process effacement. Nephrotic-range proteinuria persisted with a urine protein-to-creatinine ratio (UPCR) ranging from 5.3-7.6 g/g, including transient improvement with tacrolimus followed by relapse.
To address differentials for TMA, which include thrombotic thrombocytopenic purpura, c-HUS, drug-induced TMA, infections, nutritional deficiency, serologic workup was pursued and showed normal complement levels and ADAMTS-13 levels. The c-HUS and Anti-phospholipid antibody syndrome panels were negative. Anti-nuclear antibodies were detected at 1:320. B12 was 207 pg/mL, prompting supplementation. Genetic testing identified a heterozygous MCP/CD46 risk haplotype, which is associated with increased susceptibility to complement-mediated TMA.
Without systemic features, she was diagnosed with renal-limited complement-mediated TMA for which Eculizumab was initiated and pending repeat urine protein creatinine ratio.
Discussion
TMA may be an isolated renal process with nephrotic-range proteinuria, likely reflecting endothelial injury with secondary podocyte dysfunction. Importantly, normal complement levels do not exclude complement-mediated TMA, and underlying genetic susceptibility may contribute via a “second-hit” mechanism. CD46 serves as a cofactor for serine protease factor I-mediated cleavage of C3b and C4b to prevent further complement activation. Additionally, this gene has been linked to other TMA renal injury.
Renal-limited TMA remains under-recognized and may be misdiagnosed as a primary glomerular disease. Early identification is essential, as prompt initiation of complement inhibition can preserve renal function.