Novel therapies of diabetic nephropathy.
OBJECTIVE
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.


RESULTS
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).


CONCLUSIONS
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.
Hypertensive Diseases Unit, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637, USA.
Basil O
BO
Burney
Rigas G
RG
Kalaitzidis
George L
GL
Bakris
D000577:Amides / Q000627:therapeutic use; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008301:Maleimides / Q000627:therapeutic use; D011733:Pyridoxamine / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism
D000577:Amides; D005650:Fumarates; D007211:Indoles; D008301:Maleimides; D013481:Superoxides; C446481:aliskiren; D011733:Pyridoxamine; C099154:ruboxistaurin