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

Anne M. Schijvens, Fransje H.S. van Hesteren, Elisabeth A.M. Cornelissen, Charlotte M.H.H.T. Bootsma-Robroeks, Roger J.M. Brüggemann, David M. Burger, Saskia N. de Wildt, Michiel F. Schreuder, Rob ter Heine

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)507-515
Number of pages9
JournalPediatric Nephrology
Volume34
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019
Externally publishedYes

Keywords

  • Hematocrit
  • Kidney transplantation
  • Pediatrics
  • Tacrolimus
  • Therapeutic drug monitoring (TDM)

Fingerprint

Dive into the research topics of 'The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients'. Together they form a unique fingerprint.

Cite this