Abstract: PUB339
Allograft Loss Secondary to Atypical Hemorrhagic Necrosis
Session Information
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Sen, Aditi A., Baylor College of Medicine, Houston, Texas, United States
- Airy, Medha, Baylor College of Medicine, Houston, Texas, United States
Introduction
Atypical hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia and renal failure caused by platelet thrombi in the microcirculation of kidneys and other organs. Genetic aHUS accounts for estimated 60% of all aHUS.It is associated reported mortality rate of 25% and about 50% progress to ESRD. In these patients, aHUS reoccurs in up to 50% kidney transplant patients while graft failure occurs in 9 out of 10 patients. It is important to investigate these cases to establish etiology and improve outcomes.
Case Description
52-year-old lady with history of Lupus nephritis, ESKD received LRKT on 10/12/2021, initially admitted with gross hematuria and reduced urinary output and diarrhea for a day. Vitals were stable. Physical examination was benign. Labs: BUN 129mg/dl and creatinine 7.12 mg/dl Platelet count was 47, elevated LDH1600 and normal haptoglobin. Peripheral smear showed No schistocytes. INR was elevated to 5.9. Anti Xa: 325 (N= <190); Fibrinogen >700.
She was on Tacrolimus that was held . ADAMTS -13 test and aHUS panel was sent.
Renal biopsy resulted complete infarction of renal tissue due to coagulation necrosis and no viable cortical tissue.
Genetic panel for aHUS showed homozygosity for complement factor mutations.
She was positive for the large CFHR1-CFHR3 homozygous deletion. Factor H autoAb, ADAMTS-13 were negative.
Discussion
Genetic aHUS accounts for estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse after completing therapy and 60% progress to ESRD. Mutations in CFH, CHFR3, MCP, CFI, CFB and C3 genes predispose to the occurrence of aHUS. Our patient had CFH mutation positive in the aHUS panel.A comprehensive evaluation of the complement pathway is recommended.
In addition to the supportive care and plasma exchange, complement dysfunction needs to be addressed with specific monoclonal antibodies such as eculizumab. A study by Levi et al administered eculizumab to 12 renal transplant patients with history of aHUS confirming that eculizumab is highly effective in preventing post-transplantation aHUS recurrence.=Additional therapies are in pipeline for future and hence, these cases need to be diagnosed and treated to avoid graft failure.