C3 polymorphisms and allograft outcome in renal transplantation.
BACKGROUND
Complement activation plays a role in the development of chronic allograft nephropathy, a common cause of late allograft loss. The role of two complement component 3 (C3) allotypes, called C3F (fast) and C3S (slow) on the basis of their electrophoretic motility, in the long-term outcome of renal allografts remains controversial.


METHODS
We selected a random sample of 1147 donor and recipient pairs from the Collaborative Transplant Study DNA bank, and their DNA specimens were genotyped for the C3F and C3S alleles. The genotyping results were analyzed according to allograft outcome. Transplants were divided into four groups, according to the recipient and donor genotypes: SS recipient and FS or FF donor (the standard for comparison, since this combination has been reported to have the best outcome), SS recipient and donor, FS or FF recipient and SS donor, and FS or FF recipient and donor.


RESULTS
Baseline characteristics of the four transplant groups were similar. The hazard ratios for allograft survival in the SS recipient and FS or FF donor group as compared with the other three groups (SS recipient and donor, FS or FF recipient and SS donor, and FS or FF recipient and donor) were not significant: 0.90 (95% confidence interval [CI], 0.7 to 1.14; P=0.33), 0.87 (95% CI, 0.65 to 1.16; P=0.33), and 0.89 (95% CI, 0.65 to 1.23; P=0.48), respectively. The four groups had similar patient-survival rates and similar cumulative rates of acute rejection and allograft dysfunction, as assessed by means of serum creatinine levels.


CONCLUSIONS
Our results suggest that transplantation of FS or FF kidneys to SS recipients is not advantageous, possibly because chronic allograft nephropathy is a multifaceted disease involving the interplay of many biologic pathways.
Varagunam
Mira
M
Barts and the London School of Medicine and Dentistry and the National Health Service Trust, London, United Kingdom.
Yaqoob
Muhammad M
MM
Döhler
Bernd
B
Opelz
Gerhard
G
D000328:Adult; D003176:Complement C3 / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C038245:C3 protein, human; D003176:Complement C3; D003404:Creatinine