loading page

The reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid
  • +4
  • Sandra Nađ Škegro,
  • Luka Panezić,
  • Livija Šimičević,
  • Tvrtko Hudolin,
  • Željko Kaštelan,
  • Nada Božina,
  • Vladimir Trkulja
Sandra Nađ Škegro
University Hospital Centre Zagreb Department of Urology
Author Profile
Luka Panezić
University Hospital Centre Zagreb Department of Urology
Author Profile
Livija Šimičević
University Hospital Centre Zagreb Department of Laboratory Diagnostics
Author Profile
Tvrtko Hudolin
University Hospital Centre Zagreb Department of Urology
Author Profile
Željko Kaštelan
University Hospital Centre Zagreb Department of Urology
Author Profile
Nada Božina
University of Zagreb School of Medicine
Author Profile
Vladimir Trkulja
University of Zagreb School of Medicine

Corresponding Author:[email protected]

Author Profile

Abstract

Aim. To estimate the effect of the reduced-function polymorphism SLCO1B1 c.521T>C on the renal graft function (estimated glomerular filtration rate, eGFR) over 12 months in patients treated with mycophenolic acid (MPA). Methods. Consecutive eligible adults (≥16 years of age) engrafted over a 6-year period who received MPA as a part of maintenance immunosuppression were assessed for eGFR on 9 occasions over 12 post-transplant months. The SLCO1B1 c.521C>T variant allele carriers (treated) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and the development of eGFR (slope) was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. Results. The adjusted eGFR slopes from day 1 to day 28 (peak), and from day 28 to day 365 were practically identical in treated (n=86) and control (n=168) patients (GMR=0.99, 95%CI 0.92-1.06, and GMR=0.98, 0.94-1.01, respectively). The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in treated and controls (adjusted RR=0.94, 0.49-1.84 and RR=1.08, 0.74-1.58, respectively). The pharmacokinetic substudy did not signal that treated and control patients differed with respect to MPA clearance, peak, trough or total exposure, overall (treated n=23, control n=45), if cotreated with cyclosporine (n=17 vs. n=26) or with tacrolimus (n=8 vs. n=17). Discussion. In patients treated with MPA, variant allele SLCO1B1 c.521T>C has no effect on the 12-month renal graft function. It does not seem to affect exposure to- and safety of MPA.