Research progress on pathogenesis and new therapies of Alport syndrome / 中华肾脏病杂志

ABSTRACT

Alport syndrome (AS), also known as "eye-ear-kidney syndrome or hereditary nephritis", is a common hereditary disorder. AS is caused by pathogenic mutations of type Ⅳ collagen genes ( COL4α3, COL4α4 and COL4α5), leading to defects in the basement membrane of glomeruli, cochlea, and ocular lens. Patients present with hematuria, proteinuria, and progressive renal failure. With the redefinition of AS and the clinical application of high-throughput sequencing technology, the prevalence of AS may be much higher than the previously recognized. The specific pathogenic mechanism of AS is unknown. Recent studies have showed that type Ⅳ collagen gene mutation may lead to kidney injury by causing abnormal basement membrane components, lipid deposition, energy metabolism disorders, endoplasmic reticulum stress, inflammation and fibrosis. Renin-angiotensin system inhibitor is the main therapy of AS, but the effect is not satisfactory. The new therapeutic strategies mainly include inhibition of abnormal collagen signal transduction, reduction of endoplasmic reticulum stress in podocytes, regulation of energy metabolism, antioxidant stress, anti-inflammation and fibrosis, gene and stem cell therapy. The paper reviewed the research progress on pathogenesis and new therapies of AS.