Dipeptidyl peptidase-4 inhibition and renoprotection: the role of antifibrotic effects.

Takagaki, Yuta; Koya, Daisuke; Kanasaki, Keizo

PURPOSE OF REVIEW This article analyzes the potential beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors on renal diseases. RECENT FINDINGS 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. SUMMARY 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.