Abstract
High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4–6, 7–9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08–0.14), group 2: 0.14 (0.01–0.17), group 3: 0.17 (0.14–0.23), group 4: 0.17 (0.15–0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.
Highlights
Kidney transplantation is an optimal method of treatment in patients with end-stage chronic kidney disease (CKD) [1]
High tacrolimus intra-patient variability (IPV) is associated with accelerated progression of chronic histologic lesions in kidney transplant recipients (KTRs) [7]
The mean total weekly pill burden and median dosing frequency per day were proportional to the number of medication
Summary
Kidney transplantation is an optimal method of treatment in patients with end-stage chronic kidney disease (CKD) [1]. Long-term kidney transplant success is related to the adequate net dose of immunosuppressive drugs, as any acute rejection episode markedly worsens the distant kidney graft outcome [3,4] Both inadequate low tacrolimus trough levels within the first post-transplant year and high intra-patient variability (IPV) of tacrolimus blood levels are associated with subsequent poor long-term outcome after kidney transplantation [5,6]. An average medication burden in these patients is high, especially in the early post-transplant period [10,11] This effect is further magnified by the increasing percentage of kidney transplantations performed in patients older than 65 years [12]. We performed this cross-sectional study in a cohort of stable KTRs in order to determine whether the number of regularly prescribed medications is associated with the variability of tacrolimus blood trough levels
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