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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
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  • 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
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Luka Panezić
University Hospital Centre Zagreb Department of Urology
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Livija Šimičević
University Hospital Centre Zagreb Department of Laboratory Diagnostics
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Tvrtko Hudolin
University Hospital Centre Zagreb Department of Urology
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Željko Kaštelan
University Hospital Centre Zagreb Department of Urology
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Nada Božina
University of Zagreb School of Medicine
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Vladimir Trkulja
University of Zagreb School of Medicine

Corresponding Author:vladimir.trkulja@mef.hr

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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.