Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations

TY - JOUR

T1 - Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations

AU - Alberti, M

AU - Valoti, E

AU - Piras, R

AU - Bresin, E

AU - Galbusera, M

AU - Tripodo, C

AU - Thaiss, F

AU - Remuzzi, G

AU - Noris, M

N1 - © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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.

KW - Adult

KW - Antigens, CD46

KW - Case-Control Studies

KW - Complement Factor I

KW - DNA Primers

KW - Escherichia coli Infections

KW - Female

KW - Genetic Testing

KW - Graft Rejection

KW - Hemolytic-Uremic Syndrome

KW - Heterozygote

KW - Humans

KW - Kidney Failure, Chronic

KW - Kidney Transplantation

KW - Male

KW - Middle Aged

KW - Mutation

KW - Pedigree

KW - Prognosis

KW - Recurrence

KW - Risk Factors

KW - Shiga-Toxigenic Escherichia coli

KW - Thrombocytopenia

KW - Young Adult

U2 - 10.1111/ajt.12297

DO - 10.1111/ajt.12297

M3 - SCORING: Journal article

C2 - 23731345

VL - 13

SP - 2201

EP - 2206

JO - AM J TRANSPLANT

JF - AM J TRANSPLANT

SN - 1600-6135

IS - 8

ER -