An endothelin-transforming growth factor beta pathway in the nephrotoxicity of immunosuppressive drugs.

An endothelin-transforming growth factor beta type 1 pathway is proposed to account for cyclosporin nephrotoxicity. Cyclosporin amplifies the production of endothelin. Enhanced endothelin production accentuates acute vascular events and promotes the synthesis and activation of transforming growth factor beta type 1, contributing to acute and chronic pathology. This scheme integrates many observations, including the involvement of the renin-angiotensin pathway and other activators of endothelin production, and provides a rationale for the amelioration of cyclosporin nephrotoxicity.