title: Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model.
abstract: BACKGROUND
  Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up.
  
  
  METHODS
  Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI.
  
  
  RESULTS
  Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function.
  
  
  CONCLUSIONS
  As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I.
authors.affiliation: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Renal Medicine. Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Chris
authors.identifier: http://orcid.org/0000-0003-3262-8524
authors.initials: C
authors.lastname: Amdisen
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Keller
authors.affiliation: Zealand Pharma A/S, Glostrup, Denmark.
authors.forename: Rie Schultz
authors.initials: RS
authors.lastname: Hansen
authors.affiliation: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.affiliation: Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren Palmelund
authors.initials: SP
authors.lastname: Krag
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Møldrup
authors.affiliation: Comparative Medicines Lab, Aarhus University, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Department of Renal Medicine. Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.affiliation: Department of Renal Medicine. Aarhus University Hospital, Aarhus, Denmark.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Birn
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D015415:Biomarkers; D004151:Dipeptides; C000619914:danegaptide; D010100:Oxygen