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

## TL;DR

This study used a precise method to confirm that children with Alport syndrome consistently took their prescribed kidney disease medication.

## Contribution

A novel LCMS-based method was developed and validated to objectively verify ACEi adherence in pediatric Alport syndrome patients.

## Key findings

- High adherence to ACEi was confirmed in 96% and 95% of children at two separate measurements.
- The LCMS method accurately detected drug intake without prior notification to participants.
- All negative control samples were correctly identified, validating the method's reliability.

## Abstract

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.

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.

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.

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

A higher resolution version of the Graphical abstract is available as Supplementary information

A higher resolution version of the Graphical abstract is available as Supplementary information

The online version contains supplementary material available at 10.1007/s00467-025-07053-0.