Closely similar tacrolimus morning troughs and graft function across the recipients’ common ABCB1 polymorphisms ( c.2677G>T/A , c.1236C>T , c.3435C>T ) early after renal transplantation

Background Reports about relevance of three common and linked ABCB1 polymorphisms (c.2677G>T/A, c.1236C>T, c.3435C>T) for exposure to- and functional outcomes in tacrolimus-treated renal transplant patients are inconsistent.Methods Tacrolimus morning troughs/dose-corrected troughs and serum creatinine/estimated glomerular filtration rate (eGFR) were measured on 6th–7th and 8th–10th postoperative day in tacrolimus-mycophenolate-treated renal transplant patients. Exposure was defined as the number of ABCB1 variant alleles (three levels; 0–1 variant = control) or as diplotypes (three levels, wild-type = control). Four target trials were emulated (2 exposure definitions × 2 outcome categories) contrasting exposed and controls for ln-transformed outcomes, and for creatinine/eGFR also on natural scales. Complementary mediation analysis related exposure, troughs, and eGFR.Results The 173 enrolled patients provided 316 paired trough and creatinine/eGFR values. After correction for strong residual confounding, all GMRs (95% CrI) for troughs remained within the 0.75–1.33 range. All GMRs (95% CrI) for ln-trasformed creatinine/eGFR were within the 0.75–1.33 range. On the natural scale, creatinine/eGFR differences were within −26.5 to 26.5 μmol/L and −5.0 to 5.0 mL/min/1.73 m2, respectively. In mediation analysis, direct, indirect, and total effects were within the same ranges.Conclusions Renal transplant recipients subsetted by genotypes across the three common ABCB1 polymorphisms display closely similar tacrolimus troughs and graft function early after transplantation.