title: Brain natriuretic peptide is not reno-protective during renal ischemia-reperfusion injury in the rat.
abstract: BACKGROUND
  Acute kidney injury (AKI) occurs in 30% of patients undergoing complex cardiovascular surgery, and renal ischemia-reperfusion (I/R) injury is often a contributing factor. A recent meta-analysis observed that perioperative natriuretic peptide administration was associated with a reduction in AKI requiring dialysis in cardiovascular surgery patients. This study was designed to further clarify the potential reno-protective effect of brain natriuretic peptide (BNP) using an established rat model of renal I/R injury.
  
  
  METHODS
  The study comprised three groups (n = 10 kidneys each): (1) control (no injury); (2) I/R injury (45 min of bilateral renal ischemia followed by 3 h of reperfusion); and (3) BNP (I/R injury plus rat-BNP pretreatment at 0.01 μg/kg/min). Glomerular filtration rate (GFR) and a biomarker of AKI, urinary neutrophil gelatinase-associated lipocalin (uNGAL), were measured at baseline and at 30 minute intervals post-ischemia. Groups were compared using two-way repeated measures analysis of variance (mean ± SD, significance P < 0.05).
  
  
  RESULTS
  Baseline GFR measurements for control, I/R, and BNP groups were 1.07 ± 0.55, 0.88 ± 0.51, and 1.03 ± 0.59 mL/min (P = 0.90), respectively. Post-ischemia, GFR was significantly lower in I/R and BNP compared with controls at 30 min, 1.29 ± 0.97, 0.08 ± 0.04, and 0.06 ± 0.05 mL/min (P < 0.01), and remained lower through 3 h, 1.79 ± 0.44, 0.30 ± 0.17, and 0.32 ± 0.12 mL/min (P < 0.01). Comparing I/R to BNP groups, GFR did not differ significantly at any time point. There was no significant difference in uNGAL levels at 1 h (552 ± 358 versus 516 ± 259 ng/mL, P = 0.87) or 2 h (1073 ± 589 versus 989 ± 218 ng/mL, P = 0.79) between I/R and BNP.
  
  
  CONCLUSIONS
  BNP does not reduce the renal injury biomarker, urinary NGAL, or preserve GFR in acute renal ischemia-reperfusion injury.
authors.affiliation: Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Florida College of Medicine, Gainesville, Florida 32610-0286, USA.
authors.forename: Tad
authors.initials: T
authors.lastname: Kim
authors.forename: P Kent
authors.initials: PK
authors.lastname: Harman
authors.forename: Robert
authors.initials: R
authors.lastname: Lyons
authors.forename: Roger B
authors.initials: RB
authors.lastname: Gaskins
authors.forename: Charles E
authors.initials: CE
authors.lastname: Hobson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Evans
authors.forename: Curtis G
authors.initials: CG
authors.lastname: Tribble
authors.forename: A Ahsan
authors.initials: AA
authors.lastname: Ejaz
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Beaver
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D009195:Peroxidase