title: No Effect of Remote Ischemic Conditioning Strategies on Recovery from Renal Ischemia-Reperfusion Injury and Protective Molecular Mediators.
abstract: Ischemia-reperfusion injury (IRI) is the major cause of acute kidney injury. Remote ischemic conditioning (rIC) performed as brief intermittent sub-lethal ischemia and reperfusion episodes in a distant organ may protect the kidney against IRI. Here we investigated the renal effects of rIC applied either prior to (remote ischemic preconditioning; rIPC) or during (remote ischemic perconditioning; rIPerC) sustained ischemic kidney injury in rats. The effects were evaluated as differences in creatinine clearance (CrCl) rate, tissue tubular damage marker expression, and potential kidney recovery mediators. One week after undergoing right-sided nephrectomy, rats were randomly divided into four groups: sham (n = 7), ischemia and reperfusion (IR; n = 10), IR+rIPC (n = 10), and IR+rIPerC (n = 10). The rIC was performed as four repeated episodes of 5-minute clamping of the infrarenal aorta followed by 5-minute release either before or during 37 minutes of left renal artery clamping representing the IRI. Urine and blood were sampled prior to ischemia as well as 3 and 7 days after reperfusion. The kidney was harvested for mRNA and protein isolation. Seven days after IRI, the CrCl change from baseline values was similar in the IR (δ: 0.74 mL/min/kg [-0.45 to 1.94]), IR+rIPC (δ: 0.21 mL/min/kg [-0.75 to 1.17], p > 0.9999), and IR+rIPerC (δ: 0.41 mL/min/kg [-0.43 to 1.25], p > 0.9999) groups. Kidney function recovery was associated with a significant up-regulation of phosphorylated protein kinase B (pAkt), extracellular regulated kinase 1/2 (pERK1/2), and heat shock proteins (HSPs) pHSP27, HSP32, and HSP70, but rIC was not associated with any significant differences in tubular damage, inflammatory, or fibrosis marker expression. In our study, rIC did not protect the kidney against IRI. However, on days 3-7 after IRI, all groups recovered renal function. This was associated with pAkt and pERK1/2 up-regulation and increased HSP expression at day 7.
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Kierulf-Lassen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Marie Louise Vindvad
authors.initials: ML
authors.lastname: Kristensen
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
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000503:physiopathology; D003250:Constriction; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D051057:Proto-Oncogene Proteins c-akt