Dipeptidyl peptidase-4 inhibition and renoprotection: the role of antifibrotic effects.
This article analyzes the potential beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors on renal diseases.



The pathological significance of DPP-4, either dependent or independent on catalytic activities, on renal diseases has been reported in preclinical studies. With regard to this, we have shown that damaged endothelial cells are converted to a mesenchymal cell phenotype, which is associated with the induction of DPP-4 in endothelial cells. The endothelial mesenchymal transition may contribute to kidney fibrosis; indeed, the antifibrotic effects of DPP-4 inhibitors have been reported elsewhere. However, even though such potential benefits of DPP-4 inhibitors on renal diseases were shown in preclinical studies, clinical trials have not yet revealed significant benefits in renal hard outcomes of DPP-4 inhibitors.



To completely understand the beneficial effects of DPP-4 inhibitors, both the following studies are required: first, preclinical studies that analyze deeper molecular mechanisms of DPP-4 inhibition, and, second, clinical studies that investigate whether such potential beneficial effects of DPP-4 inhibitors are relevant to the patients in the clinic.
aDepartment of Diabetology and Endocrinology bDivision of Anticipatory Molecular Food Science and Technology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Yuta
Y
Takagaki
Daisuke
D
Koya
Keizo
K
Kanasaki
D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D018819:Dipeptidyl Peptidase 4