Liver-kidney transplantation to cure atypical hemolytic uremic syndrome

10 páginas, 8 tablas -- PAGS nros. 940-949Atypical hemolytic uremic syndrome is often associated with mutations in genes encoding complement regulatory proteins and secondary disorders of complement regulation. Progression to kidney failure and recurrence with graft loss after kidney transplantation are frequent. The most common mutation is in the gene encoding complement factor H. Combined liver-kidney transplantation may correct this complement abnormality and prevent recurrence when the defect involves genes encoding circulating proteins that are synthesized in the liver, such as factor H or I. Good outcomes have been reported when surgery is associated with intensified plasma therapy. A consensus conference to establish treatment guidelines for atypical hemolytic uremic syndrome was held in Bergamo in December 2007. The recommendations in this article are the result of combined clinical experience, shared research expertise, and a review of the literature and registry information. This statement defines groups in which isolated kidney transplantation is extremely unlikely to be successful and a combined liver-kidney transplant is recommended and also defines those for whom kidney transplant remains a viable option. Although combined liver-kidney or isolated liver transplantation is the preferred therapeutic option in many cases, the gravity of risk associated with the procedure has not been eliminated completely, and assessment of risk and benefit requires careful and individual attention. Hemolytic uremic syndrome (HUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Typical HUS follows a diarrheal illness caused by a verocytotoxin-producing bacterium, commonly Escherichia coli O157:H7, and resolves in most cases without sequelae.1 Atypical HUS (aHUS) is much less common and has a considerably worse prognosis in terms of both mortality and development of ESRD.2Mutations in genes encoding complement regulatory proteins and secondary disorders of complement regulation seem to play a central role in the pathogenesis of most cases of aHUS. Triggering of an unregulated complement cascade is thought to damage endothelium, producing microangiopathic hemolytic anemia and thrombosis. Gene mutations are identified in at least 50% of cases. The most frequently reported mutations are in the gene encoding complement factor H (CFH) and account for 50 to 60% of cases associated with documented genetic abnormalities. Less frequent are mutations in the genes encoding membrane co-factor protein (MCP) and complement factor I (CFI) and are observed in approximately 20% and 10 to 15% of the overall disease-associated mutations, respectively.3–6 More recently, gain-of-function mutations in the genes encoding the complement-activating protein complement factor B (CFB) as well as complement C3 (C3) have been reported in a few cases with aHUS.7,8 Antibodies against factor H have also been observed in patients with aHUS, particularly children, and in most cases in association with homozygous deletion of the genes encoding complement factor H–related proteins 1 and 3 (CFHR1 and CFHR3).9 Indeed, there is a growing list of the mutations, polymorphisms, and other complement abnormalities that alone or in combination may lead to aHUS.8–13. This work has been partially supported by a grant from Fondazione ART Per La Ricerca Sui Trapianti (Milan, Italy)Peer reviewe