Clinical drug investigation · 2026
Urinary MicroRNA Expression and Tacrolimus Pharmacokinetic Variability in Kidney Transplant Recipients: A Cross-sectional Study.
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Stefanović Nikola, Danković Katarina, Veličković-Radovanović Radmila, Vukelić-Nikolić Marija, Jović Maša, Vujić Stevan, Stojiljković Vladana, Mitić Branka, Cvetković Tatjana
Аннотация
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.
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.