Therapeutic landscape of Alport syndrome: current standard of care and ongoing clinical trials

Alport syndrome is an inherited collagen IV nephropathy caused by pathogenic variants in the COL4A3 , COL4A4 , and COL4A5 genes, that can lead to progressive chronic kidney disease, sensorineural hearing loss, and ocular abnormalities. Advances in population-scale genomic sequencing have demonstrated that Alport syndrome is substantially more prevalent than previously recognized, with pathogenic COL4A5 variants occurring in approximately 1 in 2,320 individuals and heterozygous COL4A3/COL4A4 variants in up to 1 in 106 individuals. Furthermore, collagen IV-related disease is increasingly identified among patients previously labelled with focal segmental glomerulosclerosis, IgA nephropathy, or CKD of unknown origin, highlighting significant underdiagnosis and the growing importance of genetic testing in nephrology practice. Contemporary management relies on nephroprotective strategies including renin–angiotensin–aldosterone system blockade, sodium–glucose cotransporter-2 inhibitors, and non-steroidal mineralocorticoid receptor antagonists. These agents reduce proteinuria and attenuate estimated glomerular filtration rate decline, thereby delaying progression to kidney failure, but they do not directly target the underlying genetic or molecular defects driving disease progression. The urgent unmet need for disease-specific therapies has stimulated extensive translational and clinical research activity in Alport syndrome. Multiple therapeutic pathways are currently being explored, including endothelin receptor antagonism, farnesoid X receptor agonism, antifibrotic therapies and podocyte-targeted approaches. Several phase 2 and phase 3 clinical trials are ongoing and represent the most advanced stage of therapeutic development in this field. In this review, we provide a concise overview of the current standard of care for AS, focusing on therapies with established nephroprotective benefit that are currently applied in clinical practice. We also summarize the contemporary clinical trial landscape in AS, with emphasis on ongoing interventional studies registered in ClinicalTrials and release in Alport Syndrome Foundation website (alportsyndorme.org) at 30th of June 2026 that are evaluating novel targeted therapies. Importantly, this review focuses exclusively on therapies undergoing clinical evaluation and does not address preclinical or experimental animal studies.