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Two-hour post dose cyclosporine monitoring does not fit all in kidney transplantation

Dario Cattaneo, Flavio Gaspari, Stefania Zenoni, Sara Baldelli, Eliana Gotti, Annalisa Perna, Norberto Perico and Giuseppe Remuzzi

Background: In transplant patients given cyclosporine (CsA), 2-hour post-dose sampling (C2) has been proposed as the most accurate single-sample surrogate marker for the area under the time–concentration profile (AUC). Further optimization of this CsA monitoring is however, required. Objectives: The study, designed in 58 stable adult kidney transplant recipients more than 1 year post-surgery, was aimed at defining the single-point sampling strategy that best predicts CsA AUC0–12, evaluating the precision of these strategies in AUC prediction according to different CsA absorption profiles, and establishing the predictivity of CsA pharmacokinetic parameters on graft outcome. Results: Regression analysis showed that C2 values (r = 0.902) best correlated with AUC0–12, whereas a lower correlation coefficient was found for C0 (r = 0.769). However, a large error in AUC prediction was documented even with the C2 equation model, with 33% of the estimations being unacceptable. Although C2 is considered a useful surrogate of CsA Cmax, only 22% of our estimations had the maximum CsA concentration at this time point, whilst 74% CsA peaked within 1 h. Of note, in ‘low’ absorbers, C0 but not C2 identified the most accurate surrogate marker for AUC0–12. In a retrospective study, multivariate logistic regression analysis of the interaction between pharmacokinetic parameters and graft function outcome showed that C0 but not C2 significantly predicted an increase in serum creatinine greater than 20% and/or a decline in glomerular filtration rate of greater than 20% at the last available follow-up as compared with baseline evaluation. Similar predictive value of C0 but not C2 was obtained considering dialysis as the end point. Conclusions: In adults, stable kidney transplant recipients, a 2 h post-dosing CsA blood level is not a universal, accurate predictor of drug exposure and graft function outcome.