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Alport syndrome (AS) is a genetic disorder responsible for up to 2.0% of kidney disease requiring renal replacement therapy. The classical phenotypic features and family history may not be present in many patients reaching ESKD (end stage kidney disease). We aim to explore kidney phenotypes, gene variants, and possible predictors of kidney failure in the genetically heterogeneous population of Uruguay.
Cross-sectional, observational study. Patients with CKD (chronic kidney disease) and a diagnosis of AS confirmed at molecular level referred to our clinic between October 2021 and April 2023 were included. Demographic, clinical, biochemical parameters and histologic characteristics of prognostic interest were collected from medical records and clinical encounters at the time of DNA extraction and in follow-up visits. The primary outcome was kidney failure.
Data from 140 patients (58 families) was retrieved, 43 cases were AS. Genetic analysis confirmed a diagnosis of AS at the molecular level in 39 cases and 4 cases had potentially pathogenic heterozygous variants in COL4A3 gene. Mean (±SD) age was 38.0±14.5 years and 55.8% were women. The most frequently affected gene was COL4A5 (47%) followed by COL4A4 (33%) and COL4A3 (12%). Nearly half of patients presented hearing loss (49%) and visual alterations (51%), and 34.9% of the patients had eGFR < 60 ml/min. Only 12 patients (27.9%) underwent a kidney biopsy, being FSGS (focal segmental glomerulosclerosis) the most common histopathological finding (18.6%). Of all patients, 12 (27.9%) reach ESKD, at a median age of 38 [IQR, 5] years. All patients who progressed to kidney failure had proteinuria (p=0.044) and a history of gross hematuria occurred more frequently (42%) in patients with ESKD (p=0.110) in comparison with patients without ESKD (16%). Deaf patients reached ESKD at a younger age (28 years) compared to patients with no hearing impairment (36 years old).
Among patients with AS, COL4A5 was the most frequently involved gene. A significant proportion of patients with AS were young when reaching ESKD, particularly those with proteinuria and gross hematuria.