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Dipeptidyl peptidase-4 inhibition and renoprotection

the role of antifibrotic effects

Takagaki, Yuta; Koya, Daisuke; Kanasaki, Keizo

Current Opinion in Nephrology and Hypertension: January 2017 - Volume 26 - Issue 1 - p 56–66
doi: 10.1097/MNH.0000000000000291
HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Dr Mark Cooper and Dr Merlin Thomas
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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.

aDepartment of Diabetology and Endocrinology

bDivision of Anticipatory Molecular Food Science and Technology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

Correspondence to Keizo Kanasaki, MD, PhD, Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Jap. an. Tel: +81 76 286 2211 (Ext. 3305); fax: +81 76 286 6927; e-mail: kkanasaki@kanazawa-med.ac.jp

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