Impact of Age-3 Urine Screening on Diagnosis and Treatment Timing in Alport Syndrome

Introduction Alport syndrome is an inherited kidney disease that leads to end-stage kidney disease (ESKD) owing to pathogenic variants in COL4A3 / 4 / 5 , which encode type IV collagen. Promptly identifying patients with Alport syndrome and starting treatment with a renin–angiotensin system inhibitor (RAS-I) is important for delaying the progression to ESKD. In Japan, public urine screening is available for all children aged 3 years old. Methods Patients genetically diagnosed with Alport syndrome at our department between August 2015 and May 2024, who were 18 years or younger, were included in the study. We evaluated their clinical and genetic characteristics and identified the circumstances under which abnormal urine findings were first detected, with a focus on the role of age-3 urine screening. Results A total of 356 patients with Alport syndrome were eligible for this study. The most common setting for detecting urine abnormalities for the first time was during age-3 urine screening (n=113, 31.7%). The inherited forms were as follows: X-linked female (43.3%), X-linked male (30.1%), autosomal dominant (19.5%), and autosomal recessive (6.2%) Alport syndrome. Additionally, 60.2% of these patients already met the criteria for RAS-I treatment at the time of urine screening. Discussion Our study showed that approximately 30% of patients with Alport syndrome had the opportunity to be diagnosed through age-3 urine screening, and among them, more than half were already eligible for RAS-I treatment. Urine screening may be an optimal method for contributing to a delay in the progression to ESKD in patients with Alport syndrome. Funding/Support Kandai Nozu receives the Grants-in-Aid for Scientific Research (KAKENHI, 23K07698), Childhood-onset, rare and intractable kidney diseases in Japan, Research on rare and intractable diseases, Health, Labour and Welfare Sciences Research Grants (23FC1047), the Japan Agency for Medical Research and Development (AMED) (Grant Number 24015773 and 22810094 and 23ek0109617s1702)