Background Tacrolimus is a calcineurinic inhibitor characterised by a narrow therapeutic window and high variability of plasmatic levels.
Purpose To assess the intra-patient variability (IPV) of tacrolimus plasmatic levels (FKplasm) in kidney-transplanted patients (KTP) during the early maintenance period (EMP), 3 to 6 months after surgery. In EMP begins a progressive reduction of immunisation to establish the future immunosuppressant dosage.
Material and methods Observational retrospective study in KTP within 2015–2017, monitored along the EMP and at least one determination of FKplasm.
The clinical data was collected from the hospital’s medical records, including kind of transplant, FKplasm and analysis date.
The FKplasm were analysed for each patient along the EMP. The mean and standard deviation of plasma concentrations, the number of blood determinations, the coefficient of variation (CV), the proportion of values lower than 5 and 7 ng/ml (P5 and P7) and the area under the concentration-estimated time (AUC-Min) were evaluated in EMP. To describe the IPV the CV was used.
The range of therapeutic FKplasm values was established between 5–20 ng/ml. The therapeutic control was considered inadequate if IPV was superior to 30% or the P7 or P5 was superior to 20%.
To evaluate the IPV and to compare the intra-patient values obtained, the analysis of variance and the Fisher–Snedecor F distribution were used (statistical analysis with SPSS).
Results Two-hundred and eleven patients and 996 tacrolimus determinations were included. The mean of FKplasm was 8.57 ng/ml (95% CI: 8.26 to 8.88) and the mean number of determinations was 4.72 (95% CI: 4.17 to 5.26) during the follow-up period.
The mean CV of FKplasm was 25.41% (95% CI: 23.09 to 27.74). A total of 31.75% (95% CI: 25.42 to 38.09) of the patients had a CV greater than 30%. The AUC-Min was 7.61 ng/ml/day (95% CI: 7.2 to 8.0).
Finally, the mean percentages of FKplasm lower than 7 ng/ml and 5 ng/ml were 27.20% (95% CI: 23.16 to 31.24) and 9.28% (95% CI: 6.49 to 12.06), respectively. The proportion of patients with values higher than 20% was 52.3% (95% CI: 45.6 to 58.8) P7 and 17.2% (95% CI: 12.3 to 21.8) P5.
The IPV of FKplasm during the EMP was higher than recommended in 31.75% of cases, similarly, 27.2% of the determinations were <7 ng/ml.
Conclusion Taking into account the limitations of this study, the early detection of patients with high IPV, or analytical values<7 ng/ml in the EMP is essential, since these are associated in the long term with a worse prognosis, leading to chronic rejection of the graft and/or greater pharmacological toxicity.
References and/or acknowledgements Thanks to all authors for their involvement.
No conflict of interest.
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