High Adherence to Angiotensin-Converting Enzyme Inhibitor in Children with Alport Syndrome: Objective Verification Using Liquid Chromatography Mass Spectrometry

Background: Kidney failure (KF) in children and adolescents leads to reduced lifespan and compromised health. Alport syndrome (AS) is the second common genetic cause of KF. 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 medication intake. Methods: Urine samples from 58 children enrolled in the EARLY PRO-TECT Alport trial were analyzed. A 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 adherence measurements. Results: 109 urine samples from patients with early stages of chronic kidney disease (mean estimated glomerular filtration rate: 130 ± 32 ml/min/1.73m) were analyzed at two different time points. All 13 negative control samples (100%) were identified correctly. Adherence to ACEi therapy was consistently high, with 98% of children showing confirmed drug intake at both the initial (48/49) and second (44/45) measurements. Conclusion: This study demonstrated that children with chronic kidney disease, when treated with ACEi within a clinical trial, maintain a high adherence to the prescribed medication. Funding: Government Support – Non-U.S.Figure 1: Illustration of adherence to RASi. Donut graphs show the proportion of (A) the overall cohort of 107 measurements, including 13 negative controls (B) correctly identified negative controls (n=13, 100%). (C) adherence and non-adherence at both time points of the study (n=94; 98% adherence), (D) adherence and non-adherence at first adherence measurement (n=49; 98% adherence), (E) adherence and non-adherence at the second adherence measurement (n=45; 98% adherence)