Related Experiment Videos
Impact of apolipoprotein(a) phenotypes on long-term renal transplant survival
Friederike Wahn1, Volker Daniel2, Florian Kronenberg3
1University Children's Hospital, Charité, Berlin, Germany.
Insights
Low molecular weight apolipoprotein(a) phenotypes in young kidney transplant recipients are linked to chronic rejection and reduced graft survival. High molecular weight phenotypes show better long-term outcomes.
Area of Science:
- Nephrology
- Cardiovascular Science
- Transplantation Immunology
Background:
- Chronic rejection (CR) limits long-term renal transplant success, sharing similarities with atherosclerosis.
- Lipoprotein(a) [Lp(a)], an atherosclerosis risk factor, has an uninvestigated role in CR.
- Plasma Lp(a) levels are primarily determined by inherited apolipoprotein(a) [apo(a)] isoforms, inversely correlating with apo(a) molecular weight.
Purpose of the Study:
- To investigate the association between apolipoprotein(a) [apo(a)] phenotypes and long-term graft survival in renal transplant recipients.
- To determine if apo(a) phenotype influences the risk of chronic rejection (CR) in kidney transplant patients.
Main Methods:
- Retrospective analysis of 327 renal transplant recipients (1982-1992).
- Identification of apolipoprotein(a) [apo(a)] isoforms (high molecular weight [HMW] vs. low molecular weight [LMW]) in patient sera.
- Comparison of long-term graft survival between HMW and LMW apo(a) phenotype groups using Kaplan-Meier and Cox regression analysis.
Main Results:
- No significant difference in overall mean graft survival between HMW and LMW apo(a) phenotypes (12.8 vs. 11.9 years, P=0.2065).
- Younger recipients (≤35 years) with LMW apo(a) phenotypes had significantly shorter mean graft survival (9.9 years) compared to HMW phenotypes (13.2 years, P=0.0156).
- In young patients, LMW apo(a) phenotypes were independently associated with an increased risk of CR (P=0.0434), irrespective of HLA mismatches, gender, or immunosuppression.
Conclusions:
- Young renal transplant recipients with low molecular weight (LMW) apolipoprotein(a) [apo(a)] phenotypes exhibit significantly reduced long-term graft survival.
- LMW apo(a) phenotypes represent an independent risk factor for chronic rejection in younger kidney transplant recipients.
- Apo(a) phenotype may be a valuable biomarker for predicting CR risk and guiding management in specific kidney transplant populations.
Abstract:
The long-term success of renal transplantation is limited because of chronic rejection (CR), which shows histologic parallels to atherosclerosis. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but its role in CR has not been investigated. Plasma levels of Lp(a) are determined 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 recipients with high molecular weight (HMW) or low molecular weight (LMW) apo(a) phenotypes were compared retrospectively. Mean (95% confidence interval) transplant 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 transplantation, mean transplant survival was more than 3 yr longer in recipients with 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 LMW 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 recipients with LMW apo(a) phenotypes have a significantly shorter long-term graft survival, regardless of the number of HLA mismatches, gender, or immunosuppressive treatment.