Managing and preventing atypical hemolytic uremic syndrome recurrence after kidney transplantation.
OBJECTIVE
Several genetic and acquired abnormalities leading to abnormal activation of the alternative pathway of complement have been identified in patients with atypical hemolytic uremic syndrome (aHUS). The purpose of this review is to shed light on how advances in the understanding of aHUS pathogenesis have impacted on prevention and cure of aHUS recurrence after kidney transplantation.


RESULTS
Studies over the past decade have shown that the risk of posttransplant recurrence of aHUS depends on the underlying genetic abnormality. The risk is high in patients with mutations in genes encoding circulating complement proteins and regulators, whereas patients with mutations in membrane cofactor protein generally show good transplant outcome. Given the poor outcome associated with recurrence, isolated renal transplantation had been contraindicated in aHUS patients. Combined kidney-liver transplantation and prophylactic plasma exchange have been used to prevent posttransplant recurrences. More recent data have provided evidence about the efficacy of the anti-C5 monoclonal antibody eculizumab in the prevention and treatment of posttransplant aHUS recurrences.


CONCLUSIONS
This review summarizes recent advances on preventing and managing aHUS recurrence after kidney transplantation and discusses the issues that still need clarification.
aIRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò', Ranica, and 'Centro Anna Maria Astori' Science and Technology Park Kilometro Rosso bUnit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Marina
M
Noris
Giuseppe
G
Remuzzi
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D065766:Atypical Hemolytic Uremic Syndrome; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation; D009154:Mutation; D010951:Plasma Exchange; D000069283:Rituximab; D055502:Secondary Prevention
D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003165:Complement System Proteins; C481642:eculizumab