Abstract: SA-PO822
Kidney-Limited Thrombotic Microangiopathy (TMA) Is Prevalent along the Spectrum of TMA and Does Not Exclude Complement Defects
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- van Doorn, Daan P.C., Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands
- 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; Expert Center for Immune-mediated Kidney Diseases and Vasculitis.
Background
The syndromes of TMA are associated with acute kidney injury and risk of ESKD. Patients typically present with systemic hemolysis, that is, thrombocytopenia and microangiopathic hemolytic anemia. Kidney-limited TMA, however, can occur but is often overlooked and undertreated. Here, we studied morphologic features on kidney biopsy and their clinical correlates in patients with TMA.
Methods
Patients with TMA on kidney biopsy were recruited from the Limburg Renal Registry and classified as definite complement-mediated (C-)TMA (i.e., ≥1 pathogenic complement gene variant), probable C-TMA (i.e., massive ex vivo C5b9 formation, either with ≥1 complement gene variant of uncertain significance or not), and secondary TMA (i.e., normal ex vivo C5b9 formation without complement gene variants). Morphologic features, including activity and chronicity indices, were studied in relation to clinical presentation and outcome.
Results
Patients were classified as definite C-TMA (N=14, 18%), probable C-TMA (N=21, 27%), or secondary TMA (N=42, 55%), including 52 (66%; n/N=8/14, 10/21, and 33/42) patients with kidney-limited TMA. Definite and probable C-TMA presented with higher creatinine (11.0 [IQR, 4.0-13.3] and 5.7 [IQR, 4.0-8.2] vs. 3.2 [IQR, 2.2-5.3] mg/dL; P<0.001) and at younger age (33 [IQR, 25-29] and 33 [IQR, 28-44] vs. 40 [IQR, 35-52] years; P=0.01) as compared to secondary TMA. Glomerular thrombosis was not associated with systemic hemolysis, but appeared more common in definite and probable C-TMA as compared to secondary TMA (79% and 76% vs. 43%; P=0.005). Morphologic features neither defined etiology nor differed between systemic TMA and kidney-limited TMA. Kidney remission, that is, recovery of kidney function and/or ≥25% increase in eGFR, occurred more often in eculizumab treated patients with definite (100% vs. 11%; P=0.001) and probable C-TMA (86% vs. 29%; P=0.009) but not secondary TMA (60% vs. 67%; P=0.7) as compared to untreated patients; chronicity indices did not predict kidney remission.
Conclusion
Kidney-limited TMA is common along the spectrum of TMA, including definite and probable C-TMA. Thus, a kidney biopsy is often needed to detect the TMA but cannot define etiology. Chronicity indices should not be used to withhold complement-specific drugs in patients with definite and probable C-TMA.
Funding
- Commercial Support – Alexion Pharmaceutical Inc. (AstraZeneca)