Defining renal phenotype in Alström syndrome

Area of Science:

• Nephrology
• Genetics
• Rare Diseases

Background:

• Alström syndrome (AS) is a rare autosomal recessive ciliopathy with diverse clinical manifestations.
• Renal disease characteristics in AS have not been systematically documented.
• This study aimed to define the onset and progression of renal disease in AS patients.

Purpose of the Study:

• To characterize the incidence, etiology, and progression of renal disease in Alström syndrome.
• To determine the relationship between age and kidney function decline in AS.
• To identify key factors associated with renal disease severity in AS.

Main Methods:

• Prospective observational cohort study utilizing national and international Alström syndrome registries.
• Cross-sectional analysis of kidney function across all age groups.
• Serial follow-up assessments of adult AS patients, including eGFR and albuminuria measurements.

Main Results:

• A rapid decline in estimated glomerular filtration rate (eGFR) was observed, averaging -16.7 mL/min/1.73 m2 per decade in males and -10.9 in females.
• 63% of adult AS patients exhibited chronic kidney disease (CKD) Stage 3 or higher.
• Structural abnormalities like nephrocalcinosis and cysts were common (63%), alongside hyperuricaemia (79%) and lower urinary tract symptoms (70%).

Conclusions:

• Renal disease is a hallmark of Alström syndrome, initiating early and progressing with age.
• AS leads to a high prevalence of advanced CKD at a young age.
• Alström syndrome should be considered in the differential diagnosis of rare genetic renal diseases.