The long-term success of renal transplantation is limited because of chroni
c rejection (CR), which shows histologic parallels to atherosclerosis. Lipo
protein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but i
ts role in CR has not been investigated. Plasma levels of Lp(a) are determi
ned mainly by the inherited isoform (phenotype) of apolipoprotein(a) [apo(a
)] and show an inverse correlation with the molecular weight of apo(a). Apo
(a) isoforms were identified in frozen sera of 327 patients who received a
renal transplant during 1982 to 1992. Long-term graft survival in recipient
s with high molecular weight (HMW) or low molecular weight (LMW) apo(a) phe
notypes were compared retrospectively. Mean (95% confidence interval) trans
plant survival was 12.8 yr(range, 11.9 to 13.6 yr) in patients with HMW and
11.9 yr (range, 10.8 to 13.1 yr) in patients with LMW apo(a) phenotypes (P
= 0.2065). In patients who were 35 yr or younger at the time of transplant
ation, mean transplant survival was more than 3 yr longer in recipients wit
h HMW apo(a) phenotypes compared with those with LMW apo(a) phenotypes (13.
2 yr [range, 12.1 to 14.4 yr] versus 9.9 yr (range, 8.5 to 11.5 yr); P = 0.
0156). In a Cox's proportional hazards regression model, the presence of LM
W phenotypes-but not gender, immunosuppression, or HLA mismatches-in young
patients was associated with a statistically significant risk of CR (P = 0.
0434). These retrospective data indicate that young renal transplant recipi
ents with LMW apo(a) phenotypes have a significantly shorter long-term graf
t survival, regardless of the number of HLA mismatches, gender, or immunosu
ppressive treatment.