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
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.