Investigation of clinical and genetic characteristics of Alport syndrome using a national registry in Japan (JP-ALPS).

BACKGROUND

Comprehensive epidemiological information regarding Alport syndrome, particularly from national cohorts, is limited.

METHODS

Utilizing a national Alport syndrome cohort in Japan established in October 2022, we analyzed clinical characteristics according to genotype. Only baseline data collected retrospectively at enrollment were used. We present longitudinal trends in estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio.

RESULTS

Of the 121 patients included, 105 (86.8%) underwent genetic testing and 82 (67.8%) had a kidney biopsy. Among those with genetic testing, 77 (73.3%) had X-linked Alport syndrome. Kidney function was normal at disease onset, with a median eGFR of 112.9 (interquartile range, 99.3-131.1) mL/min/1.73 m2. Although a steep decline during adolescence was observed in some male patients with X-linked Alport syndrome, eGFR decline was relatively slow during childhood and adolescence; the point estimate of eGFR at age 20 was 88.6 mL/min/1.73 m2. Six patients transitioned to end-stage kidney disease during the follow-up period. Eighty-one patients (66.9%) used renin-angiotensin system (RAS) inhibitors, and the rate of eGFR decline was slower after RAS inhibitor initiation. Notably, the median ages at onset and diagnosis were 3.0 and 5.1 years, respectively, because Japan's widespread urinalysis screening program for 3-year-old children enables initiation of early treatment.

CONCLUSIONS

In our cohort, which consisted mainly of patients who did not require kidney replacement therapy in childhood and adolescence, kidney function was preserved throughout this period except for some male patients with X-linked Alport syndrome. RAS inhibitor use may be associated with a reduced rate of eGFR decline.