Low C4 gene copy numbers are associated with superior graft survival in patients transplanted with a deceased donor kidney

TY - JOUR

T1 - Low C4 gene copy numbers are associated with superior graft survival in patients transplanted with a deceased donor kidney

AU - Bay, Jakob T

AU - Schejbel, Lone

AU - Madsen, Hans O

AU - Sørensen, Søren S

AU - Hansen, Jesper M

AU - Garred, Peter

PY - 2013/9

Y1 - 2013/9

N2 - Complement C4 is a central component of the classical and the lectin pathways of the complement system. The C4 protein exists as two isotypes C4A and C4B encoded by the C4A and C4B genes, both of which are found with varying copy numbers. Deposition of C4 has been implicated in kidney graft rejection, but a relationship between graft survival and serum C4 concentration as well as C4 genetic variation has not been established. We evaluated this using a prospective study design of 676 kidney transplant patients and 211 healthy individuals as controls. Increasing C4 gene copy numbers significantly correlated with the C4 serum concentration in both patients and controls. Patients with less than four total copies of C4 genes transplanted with a deceased donor kidney experienced a superior 5-year graft survival (hazard ratio 0.46, 95% confidence interval: 0.25-0.84). No significant association was observed in patients transplanted with a living donor. Thus, low C4 copy numbers are associated with increased kidney graft survival in patients receiving a kidney from a deceased donor. Hence, the degree of ischemia may influence the clinical impact of complement.

AB - Complement C4 is a central component of the classical and the lectin pathways of the complement system. The C4 protein exists as two isotypes C4A and C4B encoded by the C4A and C4B genes, both of which are found with varying copy numbers. Deposition of C4 has been implicated in kidney graft rejection, but a relationship between graft survival and serum C4 concentration as well as C4 genetic variation has not been established. We evaluated this using a prospective study design of 676 kidney transplant patients and 211 healthy individuals as controls. Increasing C4 gene copy numbers significantly correlated with the C4 serum concentration in both patients and controls. Patients with less than four total copies of C4 genes transplanted with a deceased donor kidney experienced a superior 5-year graft survival (hazard ratio 0.46, 95% confidence interval: 0.25-0.84). No significant association was observed in patients transplanted with a living donor. Thus, low C4 copy numbers are associated with increased kidney graft survival in patients receiving a kidney from a deceased donor. Hence, the degree of ischemia may influence the clinical impact of complement.

U2 - 10.1038/ki.2013.195

DO - 10.1038/ki.2013.195

M3 - Journal article

C2 - 23715124

SN - 0098-6577

VL - 84

SP - 562

EP - 569

JO - Kidney International. Supplement

JF - Kidney International. Supplement

IS - 3

ER -