title: Dipeptidyl peptidase-4 inhibitors in progressive kidney disease.
abstract: OBJECTIVE
  Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs approved for the treatment of type 2 diabetes. The main action of DPP-4 inhibitors is to increase the level of incretin hormones such as glucagon-like peptide-1 (GLP-1), thereby stimulating insulin secretion from pancreatic β cells. Recently emerging evidence suggests the pleiotropic extrapancreatic function of GLP-1 or DPP-4 inhibitors, including kidney and cardiovascular protection. Here, we review the effects of DPP-4 inhibitors on progressive kidney disease such as diabetic nephropathy from a therapeutic point of view.
  
  
  RESULTS
  A growing number of studies in animal models and human diseases have shown that DPP-4 inhibition ameliorates kidney disease by a process independent of glucose lowering. Possible mechanisms underlying such protective properties include the facilitation of natriuresis and reduction of blood pressure, and also local effects of the reduction of oxidative stress, inflammation and improvement of endothelial function in the kidney. DPP-4 inhibitors may also restore other DPP-4 substrates which have proven renal effects.
  
  
  CONCLUSIONS
  Treatment of diabetes with DPP-4 inhibitors is likely to involve a variety of extrapancreatic effects including renal protection. Such pleiotropic action of DPP-4 inhibitors might occur by both incretin-dependent and incretin-independent mechanisms. Conclusive evidence is needed to translate the favorable results from animal models to humans.
authors.affiliation: Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Makino
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Fujita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000201:enzymology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1