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. 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).
| Original language | English |
|---|---|
| Pages (from-to) | 2201-2206 |
| Number of pages | 6 |
| Journal | American Journal of Transplantation |
| Volume | 13 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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Keywords
- Complement factor I
- gene mutation
- hemolytic uremic syndrome
- kidney transplantation
- membrane cofactor protein
- Shiga-toxin
ASJC Scopus subject areas
- Transplantation
- Immunology and Allergy
- Pharmacology (medical)
Cite this
Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations. / Alberti, M.; Valoti, E.; Piras, R.; Bresin, E.; Galbusera, M.; Tripodo, C.; Thaiss, F.; Remuzzi, G.; Noris, M.
In: American Journal of Transplantation, Vol. 13, No. 8, 08.2013, p. 2201-2206.Research output: Contribution to journal › Article
}
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.
PY - 2013/8
Y1 - 2013/8
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. 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).
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. 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).
KW - Complement factor I
KW - gene mutation
KW - hemolytic uremic syndrome
KW - kidney transplantation
KW - membrane cofactor protein
KW - Shiga-toxin
UR - http://www.scopus.com/inward/record.url?scp=84881374227&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881374227&partnerID=8YFLogxK
U2 - 10.1111/ajt.12297
DO - 10.1111/ajt.12297
M3 - Article
C2 - 23731345
AN - SCOPUS:84881374227
VL - 13
SP - 2201
EP - 2206
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 8
ER -