title: Dipeptidyl peptidase-4 inhibition improves left ventricular function in chronic kidney disease.
abstract: OBJECTIVE
  Heart failure with preserved ejection fraction (HFpEF) is a common comorbidity in people with chronic kidney disease (CKD) for which no evidence-based treatment currently exists. Recently, a group of anti-hyperglycemic agents used in the treatment of Type 2 diabetes, termed incretin-based therapies, have come under scrutiny for their putative glucose-independent effects on cardiac function. In the present study, the actions of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of incretin-based therapy in preventing HFpEF induced by chronic renal impairment were investigated.
  
  
  METHODS
  Sham-operated and subtotally-nephrectomized rats were randomized to receive the DPP-4 inhibitors, linagliptin or sitagliptin for seven weeks before assessment of cardiac and renal structure and function.
  
  
  RESULTS
  Analysis of pressure-volume loops revealed that both linagliptin and sitagliptin prevented the development of cardiac diastolic dysfunction, with cardiac collagen I synthesis also being reduced by DPP-4 inhibition. These attenuating cardiac effects occurred without change in renal function or structure where, in the doses administered, neither linagliptin nor sitagliptin affected GFR decline, proteinuria, renal fibrosis or the increased urinary excretion of biomarkers of renal toxicity.
  
  
  CONCLUSIONS
  The beneficial cardiac effects of DPP-4 inhibition, in the absence of a concurrent improvement in renal dysfunction, raise the possibility that these agents may confer cardiovascular advantages in the CKD population.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Bridgit B
authors.initials: BB
authors.lastname: Bowskill
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Advani
authors.forename: Kerri
authors.initials: K
authors.lastname: Thai
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Chen
authors.forename: M Golam
authors.initials: MG
authors.lastname: Kabir
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
authors.affiliation: . advania@smh.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Advani
mesh_terms: D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D008297:Male; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000601:surgery; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors