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Background: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. Aim: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C0/D) over 6–12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. Methods: The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation. The input C0/D values were derived from CYP3A5 genotype subgroups. Results: Patients characterized by high Tac IPV and low mean C0/D over 6–12 months could have been at greater risk of lower eGFR values in a three-year period following Tx compared to the other patient groups. This effect was more pronounced in patients with a lower eGFR at the 6th month and a history of acute rejection. The proven contribution of CYP3A5 expresser genotype to low C0/D values may suggest its indirect effect on long-term graft function. Conclusion: The findings indicate that simultaneous assessment of Tac IPV, C0/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period.

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In the long-term period after kidney transplantation, a certain level of tissue inflammation and therefore the production of proinflammatory cytokines, including TNF-α, IL-1β, IL-18 and IL-2 can be found. The aim of our study was to determine the concentrations of TNF-α, IL-1β, IL-18, IL-2 and its soluble receptor (IL-2R) in renal transplant patients, regarding the length of the postoperative period. The study involved 65 patients, transplanted at least 12 months prior to our investigation, divided into three groups, regarding the time passed since the transplantation (12-24, 24-48, and >48 months consecutively). Concentrations of the cytokines in the plasma of the subjects were measured using ELISA method. Group I showed significantly higher concentrations of IL-1b compared to the III (p<0.05), IL-18 compared to the II and III (p<0.05) and TNF-a compared to the II (p<0.05). Cytokine concentrations correlated with the time passed since the transplantation (p<0.05), except for TNF-a. Interleukin-2 correlated negatively with IL-18 and immunosuppressant dosage (p<0.05). Interleukin-1b, IL-18 and TNF-α measurements should be considered for monitoring and detecting potentially subclinical allograft damage in the second year after surgery. However, the dynamics of the change of cytokine concentration may also have been altered by the components of the immunosuppressive protocols used, such as tacrolimus, which is a link that is yet to be examined.