The renal lesions of Alport syndrome

Alport syndrome is a hereditary, progressive, hematuric nephropathy characterized by glomerular basement membrane abnormalities with frequent hearing defects and ocular anomalies. The disease is associated with mutations in genes encoding the alpha3, alpha4, or alpha5 chains of type IV collagen, COL4A3, or COL4A4 in the autosomal forms of the disease, COL4A5 in the more frequent X-linked variety. Ultrastructural changes in the glomerular basement membrane and frequent abnormal expression of type IV collagen chains in renal and skin basement membranes are crucial elements for the diagnosis of Alport syndrome, determination of the mode of inheritance, and genetic counseling. Animal models have provided invaluable tools to study the mechanisms leading to progressive deterioration of the glomerular basement membrane and ultimately to renal failure, and to evaluate benefits of potential targeted therapies.