Diabetes, hypertension, and chronic kidney disease progression: role of DPP4

Am J Physiol Renal Physiol. 2017 Apr 1;312(4):F661-F670. doi: 10.1152/ajprenal.00316.2016. Epub 2017 Jan 25.


The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53" trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3). These results have spurred immense interest in the nonenzymatic and enzymatic role of DPP4 in the kidney. DPP4 is expressed predominantly in the glomeruli and S1-S3 segments of the nephron and to a lesser extent in other segments. DPP4 is known to facilitate absorption of cleaved dipeptides and regulate the function of the sodium/hydrogen exchanger-3 in the proximal tubules. DPP4, also known as CD26, has an important role in costimulation of lymphocytes via caveolin-1 on antigen-presenting cells in peripheral blood. Herein, we present our perspectives for the ongoing interest in the role of DPP4 in the kidney.

Keywords: albuminuria; diabetes; dipeptidyl peptidase 4; immune.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / enzymology
  • Antigen-Presenting Cells / immunology
  • Caveolin 1 / metabolism
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / enzymology*
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / physiopathology
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / enzymology*
  • Diabetic Nephropathies / immunology
  • Diabetic Nephropathies / physiopathology
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Disease Progression
  • Humans
  • Hypertension / drug therapy
  • Hypertension / enzymology*
  • Hypertension / immunology
  • Hypertension / physiopathology
  • Kidney / drug effects
  • Kidney / enzymology*
  • Kidney / immunology
  • Kidney / physiopathology
  • Lymphocyte Activation
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / enzymology*
  • Renal Insufficiency, Chronic / immunology
  • Renal Insufficiency, Chronic / physiopathology
  • Signal Transduction
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / metabolism


  • Caveolin 1
  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Dipeptidyl Peptidase 4