Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations. Two patients with a clinical history of D+ hemolytic uremic syndrome associated with Shiga-toxin-producing 0157:H7 E. coli and recurrence in the kidney graft carry heterozygous mutations in the genes encoding complement factor I (patient 1) and membrane cofactor protein (patient 2). © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
|Titolo:||Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations|
|Parole Chiave:||Complement factor I; gene mutation; hemolytic uremic syndrome; kidney transplantation; membrane cofactor protein; Shiga-toxin; Adult; Antigens, CD46; Case-Control Studies; Complement Factor I; DNA Primers; Escherichia coli Infections; Female; Genetic Testing; Graft Rejection; Hemolytic-Uremic Syndrome; Heterozygote; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mutation; Pedigree; Prognosis; Recurrence; Risk Factors; Shiga-Toxigenic Escherichia coli; Thrombocytopenia; Young Adult; Transplantation; Immunology and Allergy; Pharmacology (medical)|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.1111/ajt.12297|
|Appare nelle tipologie:||01 - Articolo su periodico|