Effectiveness of renin-angiotensin-aldosterone system blockers in patients with Alport syndrome: a systematic review and meta-analysis.

Abstract

Though renin-angiotensin-aldosterone system (RAAS) blockers have been considered the primary treatment for patients with Alport syndrome (AS) for a decade, there is no comprehensive review with evidence-based analysis evaluating the effectiveness of RAAS blockers in AS. A systematic review and meta-analysis was performed of published studies that compared outcomes related to disease progression between patients with AS receiving RAAS blockers with those taking non-RAAS treatment. Outcomes were meta-analyzed using the random effects models. Cochrane risk-of-bias, Newcastle-Ottawa Scale and GRADE assessment determined the certainty of evidence. A total of eight studies (1182 patients) were included in the analysis. Overall, the risk of bias was low to moderate. Compared with non-RAAS treatment, RAAS blockers could reduce the rate of progression to end-stage kidney disease (ESKD) (four studies; HR: 0.33; 95% CI: 0.24-0.45; moderate certainty evidence). After stratified by genetic types, a similar benefit was detected: male X-linked Alport syndrome (XLAS) (HR: 0.32; 95% CI: 0.22-0.48), autosomal recessive Alport syndrome (HR: 0.25; 95% CI: 0.10-0.62), female XLAS and autosomal dominant Alport syndrome (HR: 0.40; 95% CI: 0.21-0.75). In addition, RAAS blockers showed a clear gradient of benefit depending on the stage of disease at the initiation of treatment. This meta-analysis suggested that RAAS blockers could be considered as a specific therapy to delay of ESKD for AS with any genetic type, especially at the early stage of the disease, and every further more-effective-therapy would be advised to be applied on top of this standard of care.