Endothelin receptor blockade in patients with diabetic nephropathy

Diabetic nephropathy constitutes a major health care challenge. In the current review we summarize the rationale and preclinical data that suggest involvement of the endothelin (ET) system in the pathogenesis of this complication of diabetes. Early clinical studies suggest that blockade of the ET system indeed may have renoprotective effects, as reflected by a strong reduction in albumin excretion. A major challenge in the clinical development of ET receptor blockades for this indication will be to tease out the protective effects from potential off-target effects. Of particular concern is the edema formation during ET receptor blockade.