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. 2019 Mar;34(3):507-515.
doi: 10.1007/s00467-018-4117-x. Epub 2018 Oct 30.

The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients

Anne M Schijvens  1 , Fransje H S van Hesteren  2 , Elisabeth A M Cornelissen  2 , Charlotte M H H T Bootsma-Robroeks  2 , Roger J M Brüggemann  3 , David M Burger  3 , Saskia N de Wildt  4   5 , Michiel F Schreuder  2 , Rob Ter Heine  3
Affiliations

The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients

Anne M Schijvens et al. Pediatr Nephrol. 2019 Mar.

Abstract

Background: Tacrolimus is an important immunosuppressive agent with high intra- and inter-individual pharmacokinetic variability and a narrow therapeutic index. As tacrolimus extensively accumulates in erythrocytes, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. However, as hematocrit values in pediatric kidney transplant patients are highly variable after kidney transplantation, translating whole blood concentration targets without taking hematocrit into consideration is theoretically incorrect. The aim of this study is to evaluate the potential impact of hematocrit correction on tacrolimus target exposure in pediatric kidney transplant patients.

Methods: Data were obtained from 36 pediatric kidney transplant patients. Two hundred fifty-five tacrolimus whole blood samples were available, together responsible for 36 area under the concentration-time curves (AUCs) and trough concentrations. First, hematocrit corrected concentrations were derived using a formula describing the relationship between whole blood concentrations, hematocrit, and plasma concentrations. Subsequently, target exposure was evaluated using the converted plasma target concentrations. Ultimately, differences in interpretation of target exposure were identified and evaluated.

Results: In total, 92% of our patients had lower hematocrit (median 0.29) than the reference value of adult kidney transplant patients. A different evaluation of target exposure for either trough level, AUC, or both was defined in 42% of our patients, when applying hematocrit corrected concentrations.

Conclusion: A critical role for hematocrit in therapeutic drug monitoring of tacrolimus in pediatric kidney transplant patients is suggested in this study. Therefore, we believe that hematocrit correction could be a step towards improvement of tacrolimus dose individualization.

Keywords: Hematocrit; Kidney transplantation; Pediatrics; Tacrolimus; Therapeutic drug monitoring (TDM).

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Nomograph of predicted tacrolimus plasma trough concentrations corrected for hematocrit
Fig. 2
Fig. 2
Whole blood and predicted plasma AUCs0–12 h and trough concentrations compared to the target whole blood and predicted target plasma concentrations
See this image and copyright information in PMC

References

    1. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2004;43:623–653. doi: 10.2165/00003088-200443100-00001. - DOI - PubMed
    1. Krischock LA, van Stralen KJ, Verrina E, Tizard EJ, Bonthuis M, Reusz G, Hussain FK, Jankauskiene A, Novljan G, Spasojevic-Dimitrijeva B, Podracka L, Zaller V, Jager KJ, Schaefer F, ESPN/ERA-EDTA Registry Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry. Pediatr Nephrol. 2016;31:325–333. doi: 10.1007/s00467-015-3201-8. - DOI - PubMed
    1. Wallemacq P, Armstrong VW, Brunet M, Haufroid V, Holt DW, Johnston A, Kuypers D, Le Meur Y, Marquet P, Oellerich M, Thervet E, Toenshoff B, Undre N, Weber LT, Westley IS, Mourad M. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit. 2009;31:139–152. doi: 10.1097/FTD.0b013e318198d092. - DOI - PubMed
    1. Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ. An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation. 1996;62:900–905. doi: 10.1097/00007890-199610150-00005. - DOI - PubMed
    1. Barraclough KA, Isbel NM, Kirkpatrick CM, Lee KJ, Taylor PJ, Johnson DW, Campbell SB, Leary DR, Staatz CE. Evaluation of limited sampling methods for estimation of tacrolimus exposure in adult kidney transplant recipients. Br J Clin Pharmacol. 2011;71:207–223. doi: 10.1111/j.1365-2125.2010.03815.x. - DOI - PMC - PubMed

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