Jane B. Breen

ATP-binding cassette subfamily B member 1 polymorphisms do not determine cyclosporin exposure, acute rejection or nephrotoxicity after heart transplantation.

Background. We hypothesized that genetic variation of ATP-binding cassette subfamily B member 1 (ABCB1) that encodes P-glycoprotein (involved in the uptake of cyclosporin A [CsA]) contributes to trough drug concentrations and thereby to CsAs immunosuppressive and toxic effects. Methods. Three hundred thirty-seven adult heart transplant recipients were studied retrospectively. White recipients receiving CsA at month 3 and years 1 to 5 after transplantation (n=192, 168, 156, 130, 95, and 74, respectively) were then studied with respect to ABCB1 genotype or haplotype and CsA disposition. Genotyping was performed using a gel-based polymerase chain reaction method. Dose- and weight-adjusted CsA trough concentrations ([&mgr;g/L]/[mg/kg]), time to first endomyocardial biopsy-proven acute rejection episode (grade≥3A), weaning from steroids at 1 year, and renal function at 1 year posttransplant were measured. Results. An association between dose- and weight-adjusted CsA trough concentrations and ABCB1 haplotypes was found, with 12/1236, 21/2677, 26/3435 CC/GG/CC individuals having significantly higher concentrations than TT/TT/TT individuals at years 1 and 5 (68.9±26.9 vs. 54.9±19.5 and 70.6±35 vs. 50.0±12.2 [&mgr;g/L]/[mg/kg] P<0.05, respectively) There was no difference in the incidence of acute rejection, steroid weaning, or renal impairment between the genotype or haplotype groups. Conclusions. The association of ABCB1 12/1236, 21/2677, and 26/3435 CC/GG/CC haplotype with increased CsA dose- and weight-adjusted CsA trough concentrations in this group of adult white heart transplant recipients was not consistent over time and had no effect on the incidence of acute rejection or on the development of renal impairment.

The Effects of Pre- and Post-transplant Anemia on 1-Year Survival After Cardiac Transplantation

BACKGROUND Anemia is associated with a poor prognosis in heart failure. Recent studies have also suggested that anemia may be a predictor of survival after heart transplantation. METHODS We investigated whether anemia before or after orthotopic cardiac transplantation affected post-transplant survival and analyzed data from a historical cohort of 267 consecutive adult patients who underwent transplantation between 1994 and 1999. Hemoglobin levels immediately before and at 6 weeks after orthotopic cardiac transplantation were recorded. Anemia was defined as a hemoglobin level less than 12 g/dl. The outcome was all-cause mortality. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS Pre-transplant anemia was present in 26% (n= 70). One-year survival was 70% in subjects who were anemic before transplantation compared with 81% in those who were not (p = 0.03). Multivariate analysis showed a 1-year mortality hazard ratio for pre-transplant anemic subjects of 1.77 (95% confidence interval, 1.03 3.0, p = 0.038). Anemia was more prevalent after transplantation (78%). There was no difference in 1-year survival between post-transplant anemic and non-anemic subjects. CONCLUSION Anemia before, but not after transplantation, is a common independent predictor of 1-year survival in cardiac transplant patients.