Clinical Significance of the Cystic Phenotype in Alport Syndrome

Rationale & Objective Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. Study Design Retrospective cohort study. Setting & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records. Exposures Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of ≥3 cysts in each kidney. Demographic characteristics and eGFR at disease onset. Outcomes Cystic kidney phenotype in the AS and IgAN cohorts. Time to CKD stage 3b and longitudinal changes in eGFR in the AS cohort. Analytical Approach Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort. Results We studied 108 patients with AS; 76 (70%) had genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease (ADPKD). The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared to comparison group of patients with IgAN (42% vs 19%; p=0.002). Patients with cystic kidney phenotype were older and had more marked reductions in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR. Limitations Retrospective, single-center study. Conclusions Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS suggesting a possible role in cystogenesis for the genetic variants that cause this disease.