Targeted therapies in diabetic nephropathy: an update.

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Various pathways in addition to the renin-angiotensinogen system have been implicated in the pathogenesis of diabetic nephropathy. Strategies to interrupt these pathophysiological pathways are a key to the development of new targeted therapies to prevent progression of diabetic nephropathy and are on the horizon. The various pharmacological drugs tried include aliskiren, a direct renin inhibitor blocking the first step in the renin pathway, and pentoxifylline and mammalian target of rapamycin inhibitors, which have antiinflammatory properties and have shown some promising results in management of diabetic nephropathy. Others include endothelin antagonists and vitamin D analogs which have been shown to decrease urinary albumin excretion. Inhibitors of advanced glycation and oxidative stress and plasminogen activator inhibitor-1 have proved useful in animal models of diabetic nephropathy. Others include ruboxistaurin, which blocks protein kinase C overexpression. Such targeted therapies would halt and might even reverse progression of diabetic nephropathy.