The effectiveness of Cyclosporine A use in children with Alport syndrome: single center study

BACKGROUND: Alport syndrome is a non-immune genetically determined glomerulopathy caused by mutation of genes encoding α3-5 chains of collagen type IV of the basement membranes. It manifests with hematuria and/or proteinuria, progressive renal functions decrease, often in combination with hearing and vision pathology. According to world statistics the incidence of Alport syndrome is less than 1:5000 people. THE AIM: We analyzed the effectiveness of combined Cyclosporine A and nephroprotective therapy in children with Alport syndrome in comparison with nephroprotectors only. PATIENTS AND METHODS: 35 patients were enrolled in retrospective controlled comparative non-randomized single-center longitudinal study: 9 girls (26 %) and 26 boys (74 %). The median age Me was 8,7 [5,4; 13,7] years old. The patients were divided into 2 groups. Group 1 (n=25) – patients receiving Cyclosporine A and nephroprotective therapy, group 2 (n=10) – patients receiving nephroprotective therapy only. The groups did not differ statistically significantly. The observation period was 24 months. The effectiveness of therapy was assessed by reducing proteinuria. RESULTS: In group 1, the level of proteinuria decreased significantly, especially in the first 6 months. Despite gradual increase in the level of proteinuria in this group, by 24 months of follow-up, there was statistically significant difference compared to baseline (1872.0 [1195.0; 2531.0] vs 805.0 [306.0; 1504.0]; p=0.0005). Use of nephroprotectors did not change significantly the dynamics of proteinuria. In general, after 2 years, the level of proteinuria remained practically the same (1812.0 [1508.0; 2093.0] vs 1080.0 [147.0; 3141.0]; p = 0.11). Glomerular filtration rate in two groups did not change significantly during the observation period: in group 1 – 133 [108; 146] vs 123 [106; 131]; p=0.1 and in group 2 – 124 [64; 133] vs 81 [40; 102]; p=0.18. CONCLUSION: The relative safety and efficacy of combined use of Cyclosporine A in low doses and nephroprotectors was shown in children with Alport syndrome with nephrotic proteinuria and glomerular filtration rate > 60 ml/min/1.73m2, if monocomponent nephroprotective therapy was ineffective.