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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
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Impact of tacrolimus variability on pediatric heart transplant outcomes

Megan Sirota1, Caroline Heyrend2, Zhining Ou3

  • 1Department of Cardiology, Primary Children's Hospital, Salt Lake City, UT, USA.

Pediatric Transplantation
|August 14, 2021
PubMed

Insights

Elevated tacrolimus level variability (ETLV) is common in pediatric transplant patients and linked to worse outcomes like rejection and death. Monitoring ETLV can help identify high-risk individuals for better transplant management.

Area of Science:

  • Transplant medicine
  • Pharmacology
  • Immunology

Background:

  • Tacrolimus is vital for transplant success but requires precise dosing due to its narrow therapeutic index.
  • Elevated tacrolimus level variability (ETLV) is a known risk factor for adverse outcomes in transplant recipients.
  • Understanding ETLV prevalence and associations is crucial for optimizing patient care.

Purpose of the Study:

  • To determine the prevalence of elevated tacrolimus level variability (ETLV) in pediatric heart transplant (HT) recipients.
  • To identify patient-specific factors associated with ETLV.
  • To investigate the association between ETLV and poor transplant outcomes.

Main Methods:

  • Tacrolimus levels were analyzed from 118 pediatric heart transplant patients.
  • Standard deviation (SD) of tacrolimus levels (global and prediction windows) was calculated for each patient.
  • Elevated tacrolimus level variability was defined as SD ≥3.

Main Results:

  • Over half of patients (54%) exhibited elevated tacrolimus level variability (SD ≥3).
  • Patients with ETLV had significantly higher rates of rejection, cardiac allograft vasculopathy (CAV), and death compared to those without.
  • ETLV was associated with a 40% increased risk of CAV, re-transplantation, or death; increasing age correlated with higher rejection risk.

Conclusions:

  • Elevated tacrolimus level variability is prevalent in pediatric heart transplant recipients.
  • ETLV is significantly associated with increased risks of adverse transplant outcomes.
  • ETLV serves as a valuable and accessible marker for risk stratification in this population.
Abstract

Keywords:
cardiac transplantpediatric heart transplanttacrolimustacrolimus variability

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