ATP-Binding Cassette Subfamily B Member 1 Polymorphisms Do Not Determine Cyclosporin Exposure, Acute Rejection or Nephrotoxicity After Heart Transplantation

Abstract

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.

Association between renal function and CYP3A5 genotype in heart transplant recipients treated with calcineurin inhibitors

“…35 Consistent with these observations, the impact of these genetic variants on the pharmacokinetics of calcineurin inhibitors has been variable in clinical studies. 36 -38 Finally, consistent with our results, other studies in heart transplant recipients have found no association between ABCB1 G2677T and/or C3435T and post-heart transplant renal dysfunction, 13,31,38 indicating that these two genetic polymorphisms are not major modulators of calcineurin inhibitorinduced nephrotoxicity.…”

P‐glycoprotein (MDR1/ABCB1)

“…All changes of the plasma concentrations appeared to be clinically not relevant. The results from this meta-analysis are essentially supported by further studies in renal or heart transplant recipients (Taegtmeyer et al, 2010;Staatz et al, 2010;Bouamar et al, 2011;Singh et al, 2011). However, most important are physiological factors and co-medication, that is, the body weight was identified as the most important covariate and explained 35% of the random interindividual variability in cyclosporine clearance.…”

The Pharmacogenetics of Calcineurin Inhibitor–Related Nephrotoxicity

“…72 A recent retrospective single-center analysis including 294 heart transplant recipients treated with CsA also found no association between the ABCB1 1236C.T, 2677G.T/A, and 3435C.T SNPs or ABCB1 haplotype and renal function 1 year after transplantation. 73 With regard to the effect of CYP3A5 genotype on the incidence of renal dysfunction after nonrenal transplantation, even fewer data are available. Recently, Fukudo et al 74 studied 60 adult liver transplant recipients who received Tac-based immunosuppression.…”