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Kidney Week

Abstract: PO2564

Pre-Transplant Genetic Testing of Living Related Donor in a Case of Atypical Hemolytic Uremic Syndrome

Session Information

Category: Trainee Case Report

  • 1902 Transplantation: Clinical

Authors

  • Kurup, Meghna, University of Wisconsin SMPH, Madison, Wisconsin, United States
  • Mandelbrot, Didier A., University of Wisconsin SMPH, Madison, Wisconsin, United States
  • Singh, Tripti, University of Wisconsin SMPH, Madison, Wisconsin, United States
Introduction

Atypical HUS (aHUS) is a rare thrombotic microangiopathy caused by dysregulation of the alternative complement pathway either through mutations in regulatory genes or autoantibodies directed against regulatory proteins. Here we report a case of genetic testing pre-transplant in a patient who developed aHUS with variants in the CFH and PLG genes and her living related donor.

Case Description

A 27-year-old female presented to the hospital with diarrhea, abdominal pain, AKI, and microangiopathic hemolytic anemia requiring dialysis. She was initiated on eculuzimab but progressed to ESRD. Renal biopsy showed TMA with focal crescents and severe interstitial fibrosis and tubular atrophy. Workup revealed aHUS with complement dysfunction—low C3 and C4, normal CD46 and Factors H, I, and B, and no autoantibodies to CFH. Genetic testing showed mutation on exon 9 (SCR7) of CFH that has been shown to cause aHUS as well as another variant on exon 7 of PLG, which is present in 0.3% of European Americans and may be pathogenic but is of uncertain significance for her. Ten months later, she was evaluated for living related renal transplant from her brother. Since she had a mutation known to cause aHUS, genetic testing was done for her brother as part of donor evaluation. He was found to have the same mutation in CFH but not PLG, despite being asymptomatic with no hemolytic anemia, normal kidney function. The transplant was cancelled because of increased risk of disease in the future in the brother. Genetic counselling was provided to brother about his possible risk of aHUS.

Discussion

Mutations in CFH are associated with aHUS; however, it is thought that a trigger—e.g. infection or additional acquired genetic variant leads to progression to aHUS in carriers of complement gene mutations. Genetic testing is recommended for patients with aHUS to determine cause and inform long-term treatment. This patient had a combination of a variant in the complement pathway gene CFH and coagulation pathway gene PLG, while her brother, a candidate for living related donor, had the same variant in CFH. We recommend genetic testing for a living related donor if any mutation is found in the index case to minimize posttransplant recurrence or precipitation of aHUS in the donor.