aliskiren and ruboxistaurin

Chronic kidney failure remains a major health problem worldwide. Although current treatment is focused on the renin-angiotensin system, it is essential that new treatments targeted toward novel pathophysiological mechanisms are developed if we are to make significant progress in this area. In this review, we have outlined several promising new areas while emphasizing that large, randomized, well-controlled clinical trials are essential to reach a meaningful conclusion about the efficacy and safety of novel treatment.

Topics: Amides; Anticoagulants; Antihypertensive Agents; Bicarbonates; Chronic Disease; Enzyme Inhibitors; Fumarates; Glycosaminoglycans; Humans; Indoles; Iron Chelating Agents; Kidney Diseases; Kidney Failure, Chronic; Maleimides; Pentoxifylline; Phosphodiesterase Inhibitors; Protein Kinase C; Pyridones; Renin; Renin-Angiotensin System

Current therapies proven to slow the progression of diabetic nephropathy include blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Given our better understanding of the pathophysiology of diabetic nephropathy, newer therapies to treat this condition are slowly emerging.. Animal studies and a single clinical trial demonstrate efficacy of the renin inhibitor, aliskiren, to decrease a marker of nephropathy progression, that is albuminuria. On the basis of animal study results, pyridoxamine, an inhibitor of advanced glycation and ruboxistaurin, a protein kinase C inhibitor showed promise as new agent to treat nephropathy. The clinical trial results were less than gratifying, however. Sulodexide, a glycosaminoglycan, works to reduce proteinuria presumably by restoring the already reduced glycoproteins present in the glomerular basement membrane. Like other agents, sulodexide also looked promising in animal studies, but failed to demonstrate albuminuria reduction in a large multicentre clinical trial (SUN-Micro-Trial).. This review summarizes newer therapies for slowing the progression of diabetic nephropathy. Aliskiren shows promise from small clinical studies, but we await the results of the multicentre, international ALTITUDE trial in about 2012. On the basis of the results of trials only, pyridoxamine may have a chance at further evaluation, but that is also unclear.

Topics: Amides; Animals; Diabetic Nephropathies; Fumarates; Humans; Indoles; Maleimides; Pyridoxamine; Superoxides