Factors controlled for by inclusion-exclusion criteria
Drugs affecting MPA pharmacokinetics
Serum creatinine dynamics and diuresis over 5-7 postoperative days (before MPA PK assessment)
Hypoalbuminemia at baseline of MPA PK assessment
Postoperative complications, acute rejection, infectious, cardiovascular, metabolic or hepatic co-morbidity that may affect MPA PK and/or exposure to calcineurin inhibitors (CNI)
Drugs that interfere (apart from CNI) with ABCG2 – by inclusion-exclusion criteria pertinent to drugs affecting MPA PK (some are common) and comorbidities (i.e., no need for treatments)
Drugs affecting CNI pharmacokinetics – by inclusion-exclusion criteria pertinent to drugs affecting MPA PK (some are common) and comorbidities (i.e., no need for treatments)
Factors controlled for by matching/statistical adjustment
Type of MPA formulation
Estimated creatinine clearance at baseline of MPA PK assessment
Type of CNI
CNI trough concentrations at baseline of MPA PK assessment
Age and body mass index
Polymorphisms: UGT1A9 -2152/-275 diplotypes; UGT2B7 -161 genotype; ABCB1 2677 / 3435 / 1236 diplotypes; SLC01B1 521 genotype; ABCC2 -24 genotype; ABCC2 1249 genotype (recipient and donor)
Measured factors, but not included in matching/adjustment
CYP3A4*22 and CYP3A5*3 polymorphisms: a) only a few subjects overall had variant alleles. Considering that CYP3A4/5 are practically irrelevant for MPA PK, adjustments for these two polymorphisms are practically meaningless; b) potential impact of these two polymorphisms on exposure to CNIs is accounted for by matching in respect to CNI trough concentrations.
Prednisone-equivalent doses: a) doses were closely similar between ABCG2 421C>A variant carriers and wild-type controls considering raw data (Table 2). After matching, weighted medians, quartiles and ranges were closely similar in 11 variant carriers (40, 30-50, 30-60 mg/day, respectively) matched to 43 wild-type controls (30, 30-40, 20-75 mg/day, respectively); b) effects of glucocorticoids on exposure to MPA are minor/irrelevant [1,2,5]; c) possible effects on CNI troughs (e.g., CYP-induction) are accounted for by matching in respect to CNI trough concentrations.