Background <p>Kidney failure (KF) in children and adolescents leads to reduced lifespan and compromised health. Alport syndrome (AS) is a leading hereditary cause of KF in children. Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated efficacy in delaying KF in young people living with AS, but non-adherence can compromise their therapeutic benefits. To investigate the adherence to ACEi in children and adolescents with AS, a liquid chromatography-mass spectrometry (LCMS)-based method was developed for objective verification of recent medication intake at two different time points in this cohort study.</p> Methods <p>Urine samples from 58 children enrolled in the EARLY PRO-TECT Alport trial were analyzed. An LCMS-based method was established and validated to simultaneously screen and quantify both ramipril and ramiprilat in urine samples. Participants were not informed in advance of the medication intake measurements.</p> Results <p>A total of 106 urine samples from 58 patients with early stages of chronic kidney disease (mean estimated glomerular filtration rate, 130 ± 32&#xa0;mL/min/1.73&#xa0;m<sup>2</sup>) were analyzed at two different time points. All 13 negative control samples (100%; 95% confidence intervals [CI] 75.7% to 100%) were identified correctly. Adherence to ACEi at the time of sampling was consistently high, with 96% (47/49; 95% CI 86% to 99.5%) and 95% (42/44; 95% CI 84.5% to 99.4%) of children showing confirmed drug intake at initial and second adherence measurements.</p> Conclusion <p>This study demonstrated that children with chronic kidney disease, when treated with ACEi within a clinical trial, show high adherence to the prescribed medication.</p> Graphical abstract <p></p>

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High adherence to angiotensin-converting enzyme inhibitor in children and adolescents with Alport syndrome: objective verification using liquid chromatography-mass spectrometry

  • Jan Boeckhaus,
  • Burkhard Tönshoff,
  • Lutz T. Weber,
  • Dieter Haffner,
  • Lars Pape,
  • Kay Latta,
  • Henry Fehrenbach,
  • Baerbel Lange-Sperandio,
  • Matthias Kettwig,
  • Sabine König,
  • Ulrike John-Kroegel,
  • Jutta Gellermann,
  • Matthias Galiano,
  • Angelika Hafke,
  • Frank Streit,
  • Oliver Gross

摘要

Background

Kidney failure (KF) in children and adolescents leads to reduced lifespan and compromised health. Alport syndrome (AS) is a leading hereditary cause of KF in children. Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated efficacy in delaying KF in young people living with AS, but non-adherence can compromise their therapeutic benefits. To investigate the adherence to ACEi in children and adolescents with AS, a liquid chromatography-mass spectrometry (LCMS)-based method was developed for objective verification of recent medication intake at two different time points in this cohort study.

Methods

Urine samples from 58 children enrolled in the EARLY PRO-TECT Alport trial were analyzed. An LCMS-based method was established and validated to simultaneously screen and quantify both ramipril and ramiprilat in urine samples. Participants were not informed in advance of the medication intake measurements.

Results

A total of 106 urine samples from 58 patients with early stages of chronic kidney disease (mean estimated glomerular filtration rate, 130 ± 32 mL/min/1.73 m2) were analyzed at two different time points. All 13 negative control samples (100%; 95% confidence intervals [CI] 75.7% to 100%) were identified correctly. Adherence to ACEi at the time of sampling was consistently high, with 96% (47/49; 95% CI 86% to 99.5%) and 95% (42/44; 95% CI 84.5% to 99.4%) of children showing confirmed drug intake at initial and second adherence measurements.

Conclusion

This study demonstrated that children with chronic kidney disease, when treated with ACEi within a clinical trial, show high adherence to the prescribed medication.

Graphical abstract