Abstract: PO1465
Diagnostic and Risk Factors for Deregulated Complement in Thrombotic Microangiopathy
Session Information
- Glomerular Diseases: Immunology and Inflammation in IgANP, C3GP, TMA, and Nephrotic Diseases
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Timmermans, Sjoerd, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands
- van Paassen, Pieter, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands
Group or Team Name
- Limburg Renal Registry
Background
The syndromes of thrombotic microangiopathy (TMA) are diverse and represent severe endothelial damage caused by various etiologies. The early recognition of complement-mediated (C-)TMA is of utmost importance to select patients for complement inhibition. Whether or not clinicopathologic features at presentation can distinguish C-TMA from secondary TMA and/or predict the response to complement inhibition remains unknown.
Methods
Fifty-seven patients with TMA on kidney biopsy and a normal activity of von Willebrand factor cleaving protease were screened for deregulated complement using ex vivo C5b9 formation on the endothelium and genotyping. Massive ex vivo C5b9 formation and/or rare complement gene variants defined C-TMA. Clinicopathologic features that may distinguish C-TMA from secondary TMA were studied. Regression models were used to assess the prognostic value of chronic damage on kidney biopsy.
Results
C-TMA was diagnosed in 30 patients (coexisting conditions, n=26 [87%]), including 16 (53%) cases with rare complement gene variants; 27 patients had secondary TMA related to autoimmunity (n=13), hypertension (n=10), and other etiologies (n=4). Patients presented with acute kidney injury, while systemic hemolysis was uncommon in both groups (n/N=14/30 vs. n/N=6/27; P>0.05). C-TMA was linked to younger age (37 [±14] vs. 46 [±15] years; P=0.04), low plasma C3 (n/N=16/29 vs. n/N=3/22; P<0.01), and glomerular thrombosis (n/N=19/30 vs. n/N=8/27; P=0.02) as compared to secondary TMA; glomerular thrombosis, however, was common in patients with autoimmunity (n/N=6/13; P>0.05 vs. C-TMA). These characteristics, when combined, had a specificity and sensitivity for C-TMA of 100% and 33%, respectively. Eculizumab treatment was associated with clinical remission in C-TMA (n/N=12/14; P<0.01 vs. n/N=3/16 untreated patients). Morphologic features of chronic damage, i.e., glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis, did not predict prognosis; 5 out of 6 patients with C-TMA and moderate-to-severe chronicity scores treated with eculizumab recovered and/or improved kidney function.
Conclusion
Patients with TMA, low plasma C3, and glomerular thrombosis who present at younger age (i.e., <45 years) are at high risk for C-TMA. Although a kidney biopsy is often needed to detect the TMA, morphologic features of chronic damage cannot predict prognosis.