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No Effect of Remote Ischemic Conditioning Strategies on Recovery from Renal Ischemia-Reperfusion Injury and Protective Molecular Mediators.

Kierulf-Lassen C, Kristensen ML, Birn H, Jespersen B, Nørregaard R - PLoS ONE (2015)

Bottom Line: 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.This was associated with pAkt and pERK1/2 up-regulation and increased HSP expression at day 7.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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.

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Changes in creatinine clearance (CrCl) rate and plasma creatinine (pCr) after ischemia-reperfusion injury.A) Presented as the difference (δ) between CrCl rate at baseline (prior to IRI) and CrCl rate at 3 and 7 days after IRI. B) The absolute value for the CrCl rate at the different time intervals. C) The difference between pCr at baseline and pCr at 3 and 7 days after IRI. D) The absolute value for the pCr at the different time intervals. All values are expressed as mean ± SEM. Group means were compared using one-way analysis of variance followed by Bonferroni’s multiple comparison post-test or Kruskal-Wallis test with Dunn's multiple comparisons post-test. *P < 0.05 vs. sham. A paired t-test was used to test for significant differences between CrCl or pCr measured at 3 and 7 days after IRI and the baseline value within the sham group #P < 0.05. Number of animals: sham (n = 6), ischemia-reperfusion (IR; n = 8–10), IR and remote ischemic preconditioning (IR+rIPC; n = 10), IR and remote ischemic perconditioning (IR+rIPerC; n = 10).
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pone.0146109.g002: Changes in creatinine clearance (CrCl) rate and plasma creatinine (pCr) after ischemia-reperfusion injury.A) Presented as the difference (δ) between CrCl rate at baseline (prior to IRI) and CrCl rate at 3 and 7 days after IRI. B) The absolute value for the CrCl rate at the different time intervals. C) The difference between pCr at baseline and pCr at 3 and 7 days after IRI. D) The absolute value for the pCr at the different time intervals. All values are expressed as mean ± SEM. Group means were compared using one-way analysis of variance followed by Bonferroni’s multiple comparison post-test or Kruskal-Wallis test with Dunn's multiple comparisons post-test. *P < 0.05 vs. sham. A paired t-test was used to test for significant differences between CrCl or pCr measured at 3 and 7 days after IRI and the baseline value within the sham group #P < 0.05. Number of animals: sham (n = 6), ischemia-reperfusion (IR; n = 8–10), IR and remote ischemic preconditioning (IR+rIPC; n = 10), IR and remote ischemic perconditioning (IR+rIPerC; n = 10).

Mentions: All animals survived until termination of the study. IRI was associated with a significant decrease in CrCl rate from baseline to day 3 compared with the sham group (Fig 2A). The decline in CrCl rate was similar in the IR (δ: -1.59 mL/min/kg [-2.55 to -0.64]), IR+rIPC (δ: -1.19 mL/min/kg [-2.22 to -0.15], p > 0.9999), and IR+rIPerC (δ: -1.48 mL/min/kg [-2.17 to -0.79], p > 0.9999) groups at day 3. At day 7, all groups exposed to IRI recovered a CrCl rate similar to their respective baseline values (IR group, δ: 0.74 mL/min/kg [-0.45 to 1.94], p = 0.18; IR+rIPC group, δ: 0.21 mL/min/kg [-0.75 to 1.17], p = 0.63; and IR+rIPerC group, δ: 0.41 mL/min/kg [-0.43 to 1.25], p = 0.30) (Fig 2B and Table 3). Of note, the sham group displayed a significantly increased CrCl rate from baseline to study end (δ: 3.24 [1.66 to 4.82] mL/min/kg, p = 0.0052). The pCr results are presented in Fig 2C and 2D and correspond to the results based on the CrCl rate.


No Effect of Remote Ischemic Conditioning Strategies on Recovery from Renal Ischemia-Reperfusion Injury and Protective Molecular Mediators.

Kierulf-Lassen C, Kristensen ML, Birn H, Jespersen B, Nørregaard R - PLoS ONE (2015)

Changes in creatinine clearance (CrCl) rate and plasma creatinine (pCr) after ischemia-reperfusion injury.A) Presented as the difference (δ) between CrCl rate at baseline (prior to IRI) and CrCl rate at 3 and 7 days after IRI. B) The absolute value for the CrCl rate at the different time intervals. C) The difference between pCr at baseline and pCr at 3 and 7 days after IRI. D) The absolute value for the pCr at the different time intervals. All values are expressed as mean ± SEM. Group means were compared using one-way analysis of variance followed by Bonferroni’s multiple comparison post-test or Kruskal-Wallis test with Dunn's multiple comparisons post-test. *P < 0.05 vs. sham. A paired t-test was used to test for significant differences between CrCl or pCr measured at 3 and 7 days after IRI and the baseline value within the sham group #P < 0.05. Number of animals: sham (n = 6), ischemia-reperfusion (IR; n = 8–10), IR and remote ischemic preconditioning (IR+rIPC; n = 10), IR and remote ischemic perconditioning (IR+rIPerC; n = 10).
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pone.0146109.g002: Changes in creatinine clearance (CrCl) rate and plasma creatinine (pCr) after ischemia-reperfusion injury.A) Presented as the difference (δ) between CrCl rate at baseline (prior to IRI) and CrCl rate at 3 and 7 days after IRI. B) The absolute value for the CrCl rate at the different time intervals. C) The difference between pCr at baseline and pCr at 3 and 7 days after IRI. D) The absolute value for the pCr at the different time intervals. All values are expressed as mean ± SEM. Group means were compared using one-way analysis of variance followed by Bonferroni’s multiple comparison post-test or Kruskal-Wallis test with Dunn's multiple comparisons post-test. *P < 0.05 vs. sham. A paired t-test was used to test for significant differences between CrCl or pCr measured at 3 and 7 days after IRI and the baseline value within the sham group #P < 0.05. Number of animals: sham (n = 6), ischemia-reperfusion (IR; n = 8–10), IR and remote ischemic preconditioning (IR+rIPC; n = 10), IR and remote ischemic perconditioning (IR+rIPerC; n = 10).
Mentions: All animals survived until termination of the study. IRI was associated with a significant decrease in CrCl rate from baseline to day 3 compared with the sham group (Fig 2A). The decline in CrCl rate was similar in the IR (δ: -1.59 mL/min/kg [-2.55 to -0.64]), IR+rIPC (δ: -1.19 mL/min/kg [-2.22 to -0.15], p > 0.9999), and IR+rIPerC (δ: -1.48 mL/min/kg [-2.17 to -0.79], p > 0.9999) groups at day 3. At day 7, all groups exposed to IRI recovered a CrCl rate similar to their respective baseline values (IR group, δ: 0.74 mL/min/kg [-0.45 to 1.94], p = 0.18; IR+rIPC group, δ: 0.21 mL/min/kg [-0.75 to 1.17], p = 0.63; and IR+rIPerC group, δ: 0.41 mL/min/kg [-0.43 to 1.25], p = 0.30) (Fig 2B and Table 3). Of note, the sham group displayed a significantly increased CrCl rate from baseline to study end (δ: 3.24 [1.66 to 4.82] mL/min/kg, p = 0.0052). The pCr results are presented in Fig 2C and 2D and correspond to the results based on the CrCl rate.

Bottom Line: 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.This was associated with pAkt and pERK1/2 up-regulation and increased HSP expression at day 7.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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.

Show MeSH
Related in: MedlinePlus