Pharmacogenomics · 2026
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.
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Penezić Luka, Nađ Škegro Sandra, Ganoci Lana, Šimičević Livija, Lovrić Mila, Božina Nada, Trkulja Vladimir
Аннотация
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.
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.