title: Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations.
abstract: 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.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Disease Aldo e Cele Daccò and Centro Anna Maria Astori, Bergamo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Alberti
authors.forename: E
authors.initials: E
authors.lastname: Valoti
authors.forename: R
authors.initials: R
authors.lastname: Piras
authors.forename: E
authors.initials: E
authors.lastname: Bresin
authors.forename: M
authors.initials: M
authors.lastname: Galbusera
authors.forename: C
authors.initials: C
authors.lastname: Tripodo
authors.forename: F
authors.initials: F
authors.lastname: Thaiss
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.forename: M
authors.initials: M
authors.lastname: Noris
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D017244:Complement Factor I / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D004927:Escherichia coli Infections / Q000150:complications* / Q000235:genetics / Q000382:microbiology; D005260:Female; D005820:Genetic Testing; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology; D006463:Hemolytic-Uremic Syndrome / Q000150:complications* / Q000235:genetics / Q000382:microbiology; D006579:Heterozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D054323:Shiga-Toxigenic Escherichia coli; D013921:Thrombocytopenia / Q000150:complications / Q000235:genetics / Q000382:microbiology; D055815:Young Adult
chemical_list: C497857:CD46 protein, human; D017931:DNA Primers; D051916:Membrane Cofactor Protein; C493611:CFI protein, human; D017244:Complement Factor I
keywords: Complement factor I; Shiga-toxin; gene mutation; hemolytic uremic syndrome; kidney transplantation; membrane cofactor protein