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Background <p>Dysregulation of specific microRNAs and the intraindividual (IPV) and interindividual pharmacokinetic variability of tacrolimus (Tac) have been associated with unfavorable long-term outcomes after kidney transplantation. It remains unknown whether the effects of Tac pharmacokinetic variability are reflected in microRNA expression.</p> Objective <p>The primary objective was to analyze the correlation between urinary microRNA (miR-21-5p, miR-142-3p, miR-155-5p, and miR-204-5p) relative expression levels in the long term and Tac pharmacokinetic variability parameters within the early period after kidney transplantation. Secondarily, correlation between urinary microRNA expression and long-term graft function were analyzed.</p> Methods <p>In a cross-sectional study, the urinary microRNA expression levels were determined in 50 kidney transplant recipients in the long-term period after kidney transplantation and in 12 healthy controls. Patients were divided based on the Tac IPV and metabolic phenotype, defined by Tac dose-adjusted concentration (<i>C</i><sub>0</sub>/<i>D</i>) at the 3rd post-transplantation month.</p> Results <p>Urinary expression of miR-142-3p (<i>p</i> = 0.022) and miR-204-5p (<i>p</i> = 0.007), but not miR-21-5p and miR-155-5p, differed significantly between patients in the long-term post-transplantation period and healthy controls. Patients characterized by fast/intermediate Tac metabolic phenotype had decreased urinary miR-204-5p expression compared to slow metabolizers (<i>p</i> = 0.007; <i>p</i> = 0.005, respectively). Patients with estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m<sup>2</sup> demonstrated significantly higher log-transformed expression of miR-204-5p compared to those with eGFR &lt; 45 mL/min/1.73 m<sup>2</sup> (<i>p</i> = 0.003).</p> Conclusion <p>This study indicated that the urinary expression levels of miR-142-3p and miR-204-5p were significantly different between kidney transplant recipients and healthy controls. Additionally, urinary miR-204-5p expression may be correlated with graft function in the long‑term post‑transplantation period, as well as with early Tac <i>C</i><sub>0</sub>/<i>D</i> values.</p>

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Urinary MicroRNA Expression and Tacrolimus Pharmacokinetic Variability in Kidney Transplant Recipients: A Cross-sectional Study

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Nikola Stefanović,
  • Katarina Danković,
  • Radmila Veličković-Radovanović,
  • Marija Vukelić-Nikolić,
  • Maša Jović,
  • Stevan Vujić,
  • Vladana Stojiljković,
  • Branka Mitić,
  • Tatjana Cvetković

摘要

Background

Dysregulation of specific microRNAs and the intraindividual (IPV) and interindividual pharmacokinetic variability of tacrolimus (Tac) have been associated with unfavorable long-term outcomes after kidney transplantation. It remains unknown whether the effects of Tac pharmacokinetic variability are reflected in microRNA expression.

Objective

The primary objective was to analyze the correlation between urinary microRNA (miR-21-5p, miR-142-3p, miR-155-5p, and miR-204-5p) relative expression levels in the long term and Tac pharmacokinetic variability parameters within the early period after kidney transplantation. Secondarily, correlation between urinary microRNA expression and long-term graft function were analyzed.

Methods

In a cross-sectional study, the urinary microRNA expression levels were determined in 50 kidney transplant recipients in the long-term period after kidney transplantation and in 12 healthy controls. Patients were divided based on the Tac IPV and metabolic phenotype, defined by Tac dose-adjusted concentration (C0/D) at the 3rd post-transplantation month.

Results

Urinary expression of miR-142-3p (p = 0.022) and miR-204-5p (p = 0.007), but not miR-21-5p and miR-155-5p, differed significantly between patients in the long-term post-transplantation period and healthy controls. Patients characterized by fast/intermediate Tac metabolic phenotype had decreased urinary miR-204-5p expression compared to slow metabolizers (p = 0.007; p = 0.005, respectively). Patients with estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 demonstrated significantly higher log-transformed expression of miR-204-5p compared to those with eGFR < 45 mL/min/1.73 m2 (p = 0.003).

Conclusion

This study indicated that the urinary expression levels of miR-142-3p and miR-204-5p were significantly different between kidney transplant recipients and healthy controls. Additionally, urinary miR-204-5p expression may be correlated with graft function in the long‑term post‑transplantation period, as well as with early Tac C0/D values.