Date: Monday, June 3, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Eculizumab has revolutionized the management of atypical Hemolytic Uremic Syndrome (aHUS). In 2012, the French aHUS Study Group issued recommendations to advocate a pro-transplantation policy in aHUS patients, based on the prophylactic use of eculizumab according to a highly individualized risk stratification. The same strategy was recently adopted by the 2016 KDIGO guidelines, but has never been assessed. The lack of controlled trials and population-based studies has precluded any assessment of eculizumab impact on aHUS renal epidemiology.
*Methods: A nationwide, retrospective, multicenter study was conducted, involving 34 French nephrology centers. Clinicians were contacted to update follow-up. Inclusion criteria were the following: 1- Diagnosis of aHUS; 2- Extensive complement work-up; 3- Aged of 18 years old or older between 01/01/2007 and 01/01/2016.
*Results: Over the study decade, 397 patients were identified from 33 centers. Among them, 33 were lost to follow-up and 39 died before the end of the study period. Lost-to-follow-up were mostly patients with functioning native kidneys, with either no or MCP mutations, and one third were in transition from pediatric to adult care. In contrast, those who died during the study period were primarily on chronic dialysis, and most frequently had complement alternative pathway dysregulation. During the study period, 175 de novo cases and 43 transfers from pediatric to adult joined the cohort. Hence, the French aHUS cohort increased from 179 to 325 patients between 01/01/2007 and 01/01/2016. The frequency of aHUS patients on chronic dialysis significantly decreased between 2012 and 2016, dropping from 34 to 16% (p<0.0001). The distribution and frequency of complement abnormalities did not change over this period and could not account for the better renal outcome. In the meantime, the proportion of transplant recipients among patients with end stage renal disease (ESRD) increased from 46.2 to 72.3% (p<0.0001) in all aHUS cases and from 21.7 to 60.3% (p<0.0001) in those with CFH pathogenic variants. Notably, the use of eculizumab in transplanted recipients increased from 20% to 44% in all aHUS cases and from 38.5 to 83% in the carriers of CFH variants between 2012 and 2016. In contrast, renal transplant recipients with MCP variant were not treated with eculizumab, given the related low risk of recurrence, and the proportion of transplanted patients among MCP carriers with ESRD did not change over this period.
*Conclusions: This large multicenter study shows the dramatic changes in aHUS renal outcomes in the eculizumab era. The transplanted aHUS population has now significantly outnumbered the dialysis aHUS population, especially among the carriers of high-risk gene variants.
To cite this abstract in AMA style:Zuber J, Frimat M, Gatault P, Kamar N, Couzi L, Jourde-Chiche N, Chatelet V, Caillard S, Gaisne R, Bertrand D, Bamoulid J, Louis M, Pouteil-Noble C, Legendre C, Peraldi M, Rondeau E, Quintrec MLe, Frémeaux-Bacchi V. Breakthrough Changes in the Access to Transplantation for the Patients with Atypical Hemolytic Uremic Syndrome in the Eculizumab Era [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/breakthrough-changes-in-the-access-to-transplantation-for-the-patients-with-atypical-hemolytic-uremic-syndrome-in-the-eculizumab-era/. Accessed May 16, 2021.
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