Alport Syndrome Family Screening and Management: Experience of a Tertiary Center

Alport syndrome (AS) is one of the most common causes of inherited chronic kidney disease. Timely diagnosis and treatment of this condition can significantly influence its natural course. The evaluation of at-risk family members allows for the identification of new patients and the initiation of renoprotective measures that help prevent the progression of kidney disease. The aim of this study was to describe the implementation and results of cascade screening among at-risk relatives of a cohort of patients with AS followed at our unit.

This is a prospective, single-center study conducted at Nephrology Department, Health Local Unit Gaia/Espinho. We provided patients with letters intended for their first-degree relatives, highlighting the benefits of a referral for renal impairment assessment and genetic counseling. A total of 93 at-risk relatives underwent evaluation through biochemical testing (kidney function and urinalysis abnormalities) and were offered molecular screening for the familial COL4 variant following genetic counseling. Clinical, genetic, and laboratory data were systematically collected.

Seventy-six (81.7%) at-risk relatives underwent molecular evaluation. A positive molecular test was achieved in 52 (68.4%) relatives, whereas the familial variant was excluded in 24 (31.6%) individuals. 9 (9.6%) individuals declined to proceed with screening and 8 (8.6%) experienced delay in obtaining their results. Among those with a positive molecular screening, 36.5% (n = 19) had urinary protein-creatinine ratio > 0.1 g/g creatinine and 13.5% (n = 7) had glomerular filtration rate (by the CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] 2021 equation) < 60 mL/min/1.73 m². 30 (57.7%) relatives initiated treatment with a renin-angiotensin-aldosterone system inhibitor. These individuals were older, had higher levels of proteinuria, and had a lower glomerular filtration rate at baseline.

The relatively small size of this series from a single unit. The cascade screening based on a patient-led approach may not extent to all the at-risk relatives.

Cascade screening of relatives of patients with AS is an effective strategy for identifying individuals with ongoing kidney disease or those at risk of future renal impairment. This approach enables the early initiation of nephroprotective measures and ensures timely access to appropriate genetic counseling.