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

Am J Transplant. 2013 Aug;13(8):2201-6. doi: 10.1111/ajt.12297. Epub 2013 Jun 3.

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.

Keywords: Complement factor I; Shiga-toxin; gene mutation; hemolytic uremic syndrome; kidney transplantation; membrane cofactor protein.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Complement Factor I / genetics*
  • DNA Primers / chemistry
  • DNA Primers / genetics
  • Escherichia coli Infections / complications*
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / microbiology
  • Female
  • Genetic Testing
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology
  • Hemolytic-Uremic Syndrome / complications*
  • Hemolytic-Uremic Syndrome / genetics
  • Hemolytic-Uremic Syndrome / microbiology
  • Heterozygote
  • Humans
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation
  • Male
  • Membrane Cofactor Protein / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Pedigree
  • Prognosis
  • Recurrence
  • Risk Factors
  • Shiga-Toxigenic Escherichia coli
  • Thrombocytopenia / complications
  • Thrombocytopenia / genetics
  • Thrombocytopenia / microbiology
  • Young Adult

Substances

  • CD46 protein, human
  • DNA Primers
  • Membrane Cofactor Protein
  • CFI protein, human
  • Complement Factor I