Complement Genes Strongly Predict Recurrence and Graft Outcome in Adult Renal Transplant Recipients with Atypical Hemolytic and Uremic Syndrome |
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| Authors: | M. Le Quintrec J. Zuber B. Moulin N. Kamar M. Jablonski A. Lionet V. Chatelet C. Mousson G. Mourad F. Bridoux E. Cassuto C. Loirat E. Rondeau M. Delahousse V. Frémeaux‐Bacchi |
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| Affiliation: | 1. Néphrologie et Transplantation Rénale, , H?pital Foch, Suresnes, France;2. INSERM U255, Cordeliers Biomedical Research Center, , Paris;3. Transplantation Rénale, H?pital Necker, , Paris, France;4. Service de Néphrologie et Transplantation Rénale Strasbourg, , France;5. Service de Néphrologie, Dialyse et Transplantation d'Organes, H?pital Rangueil, , Toulouse, France;6. INSERM U1043,IFR‐BMT, CHU Purpan, , Toulouse, France;7. Néphrologie et Transplantation rénale CHU Calmette, Lille, , France;8. Néphrologie et Transplantation rénale CHU Caen, , Caen, France;9. Néphrologie et Transplantation rénale CHU Dijon, , Dijon, France;10. Néphrologieet Transplantation rénale, H?pital Lapeyronie, , Montpellier, France;11. Service de Néphrologie et Transplantation rénale, CHU de Poitiers, , France;12. Service de Néphrologie et Transplantation rénale, CHU de Nice, Nice, , France;13. Assistance Publique‐H?pitaux de Paris, H?pital Robert Debré, Université Paris 7, Service de Néphrologie, , Paris, France;14. Service de Néphrologie et Transplantation rénale, H?pital Tenon, , Paris, France;15. Assistance Public‐Hopitaux de Paris, H?pital Européen Georges‐Pompidou, Laboratoire d'Immunologie, , Paris, France |
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| Abstract: | Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor‐protein (MCP), C3 and factor B (CFB). At 5 years, death‐censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M‐TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence‐related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies. |
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| Keywords: | Acute rejection atypical hemolytic and uremic syndrome endothelial cell damage mutations and polymorphisms in complement alternative pathway renal transplantation thrombotic microangiopathy |
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