Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy

Purpose of review Recent molecular genetic studies have shown that mutations in type IV collagen account for a significant proportion of patients with persistent glomerular hematuria. This review will discuss the implications of these findings for the diagnosis and management of persistent glomerular hematuria. Recent findings Type IV collagen mutations are associated with a continuum of disease severity. Heterozygous mutations typically cause isolated, nonprogressive hematuria. Mutations in both alleles of the autosomal type IV collagen genes, or hemizygous mutations in the X-linked gene encoding the alpha5 chain of type IV collagen, result in progressive renal disease that is often associated with sensorineural deafness (Alport syndrome). Animal models of Alport syndrome have begun to provide insights into the pathogenesis of end-stage renal disease in Alport syndrome, with potentially important implications for therapy. Summary Recognition that glomerular hematuria frequently has a genetic basis is important for accurate genetic counseling, early identification of individuals at risk for end-stage renal disease development, and institution of therapies to delay the onset of ESRD.