Abstract: FR-PO823
Thrombotic Microangiopathy (TMA) After Kidney Transplant: A 10-Year Experience
Session Information
- Transplantation: Clinical - Outcomes
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Rajashekar, Gaurav, Washington University in St Louis, St Louis, Missouri, United States
- Lynn, Nyein Chann Wai, Washington University in St Louis, St Louis, Missouri, United States
- Flores, Karen, Washington University in St Louis, St Louis, Missouri, United States
- Merzkani, Massini, Washington University in St Louis, St Louis, Missouri, United States
- Delos Santos, Rowena B., Washington University in St Louis, St Louis, Missouri, United States
- Java, Anuja, Washington University in St Louis, St Louis, Missouri, United States
Background
TMA is primary when a genetic or acquired defect is identified [e.g. complement genetic variants in atypical hemolytic uremic syndrome (aHUS)] or secondary when occurring in the setting of infection, malignancy, or drugs. Kidney transplant is associated with multiple triggers such as drugs, rejection, or infections, making it challenging to distinguish aHUS from secondary TMAs. This distinction is critical since aHUS is non-responsive to conservative measures. We report our approach to TMA evaluation and demonstrate how comprehensive analyses can facilitate clinical decision-making regarding treatment and recurrence risk.
Methods
Between 2011 and 2020, pre-transplant patients with TMA in the native kidney and post-transplant patients with recurrent or de novo TMA were evaluated. Genetic testing was conducted using the clinically validated aHUS panel. Variants were classified based on the American College of Medical Genetics (ACMG) guidelines.
Results
69 patients (41 post-transplant and 28 pre-transplant) underwent genetic testing (Table 1). 11 of 69 had a known aHUS diagnosis; 19 patients (27.5%) were (mis)diagnosed as hypertensive nephrosclerosis and nine (13%) developed ESKD after preeclampsia. 42 patients (60.8%) carried a complement genetic variant and 10 patients (14.4%) harbored a Factor H autoantibody (Table 2). 26 of 42 (61.9%) were classified as variants of unclear significance (VUS). A systematic antigenic and structure-function analysis of the VUS determined their clinical significance, re-categorized them as pathogenic or benign and guided treatment decisions (Fig 1).
Conclusion
1) Patients with ESKD due to HTN/preeclampsia or another TMA whose evolution is aggressive should be evaluated for complement defects. 2) Functional assessment of VUS defines their clinical significance, aids in diagnosis, informs disease etiology, facilitates assessment of recurrence risk and helps to determine treatment.
Funding
- Private Foundation Support