Abstract
Despite major advances in the understanding of the molecular mechanisms that underpin the development of diabetic kidney disease, current best practice still leaves a significant proportion of patients with end-stage kidney disease requiring renal replacement therapy. This is on a background of an increasing diabetes epidemic worldwide. Although kidney failure is a major cause of morbidity the main cause of death remains cardiovascular in nature. Hence, diabetic therapies which are both “cardio-renal” protective seem the logical way forward. In this review, we discuss the dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4inh), which are glucose-lowering agents used clinically and their role in diabetic kidney disease with specific focus on renoprotection and surrogate markers of cardiovascular disease. We highlight the novel pleiotropic effects of DPP4 that make it an attractive additional target to combat the fibrotic and inflammatory pathways in diabetic kidney disease and also discuss the current literature on the cardiovascular safety profile of DPP4inh. Clearly, these observed renoprotective effects will need to be confirmed by clinical trials to determine whether they translate into beneficial effects to patients with diabetes.
Highlights
Renal Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
Dipeptidyl peptidase 4 inhibitors (DPP4inh) have benefits beyond glucose lowering as dipeptidyl peptidase 4 (DPP4) cleaves a host of peptides/substrates in addition to Glucagon like peptide 1 (GLP-1), resulting in a broad range of altered biological functions
We focus on the pleiotropic properties of DPP4 beyond glucose lowering with specific reference to renoprotection and cardiovascular aspects
Summary
Blood glucose is tightly regulated by a number of mechanisms including the incretin system of hormones that are secreted in response to a meal. Dipeptidyl peptidase 4 inhibitors (DPP4inh) are novel oral diabetic agents used to lower blood glucose in patients with type 2 diabetes mellitus. They inhibit DPP4, which degrades GLP-1 resulting in raised endogenous GLP-1. Identified substrates include GLP-1, regulated on activation, normal T cell expressed and secreted (RANTES), which is relevant in renal disease [3, 4], brain natriuretic peptide 1–32 [5, 6], neuropeptide Y [7], high mobility group protein 1 (HMGB1) [8], and Substance P [9]. DPP4 is known to interact with adenosine deaminase [14], caveolin 1 [15, 16], cation independent mannose 6 phosphate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
