Importance of 3-Year-Old Urinalysis in Diagnosing Alport Syndrome

Background: Alport syndrome (AS) is an inherited kidney disease caused by pathogenic variants in COL4A3, COL4A4, and COL4A5, which encode the α3, α4, and α5 chains of type IV collagen. The prevalence is estimated at 1 in 5000 individuals, with autosomal dominant (ADAS), autosomal recessive (ARAS), and X-linked (XLAS) forms. Symptoms typically begin with hematuria in the early stages, progressing to increased proteinuria and eventual kidney failure. Renin-Angiotensin-Aldosterone System inhibitors can delay at which kidney failure occurs, underscoring the importance of early diagnosis and intervention, especially in patients with proteinuria. In Japan, a mass urinalysis is available for all 3-year-old children and annually for all elementary to high school students, and the 3-year-olds urinalysis has been shown to be potentially useful in the early detection of AS. Methods: We examined diagnostic events in 337 cases of AS diagnosed by genetic testing from August 2015 to September 2023, with patients aged 18 years or younger. Results: Among the 337 cases, 175 were males (52%), and the median age was 6 years. The most common event for detecting urinary abnormalities was the 3-year-old urine test, accounting for 102 cases (30%). Other events included the incidental detection of urinary abnormalities during the examination of other diseases (77 cases, 23%), episodes of macroscopic hematuria (76 cases, 23%), school urine tests (18 cases, 5%), and nursery urine tests (18 cases, 5%). Among the 102 cases identified by the 3-year-old urine test, the breakdown of each genetic form was XLAS males (29%), XLAS females (44%), ADAS (20%), and ARAS (7%). Of these, 42 cases showed both hematuria and proteinuria, with XLAS males accounting for 15 out of 30 cases (50%), XLAS females for 15 out of 45 cases (33%), ADAS for 6 out of 20 cases (30%), and ARAS for 6 out of 7 cases (86%). Conclusion: The 3-year-old urine test is the most common diagnostic event for AS, encompassing all genetic forms. The proportion of cases with proteinuria is higher in ARAS and XLAS males, but it is present in all genetic forms. In over 40% of cases, urinary protein is already observed, enabling early intervention. It is important that the benefits of the 3-year-old urine test for the early detection of AS.