Is ischemic preconditioning of the kidney clinically relevant?

Kosieradzki, Maciej; Ametani, Mary S.; Southard, James H.; Mangino, Martin J.

doi:10.1067/msy.2003.93

Cited by 37 publications

(24 citation statements)

References 33 publications

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“…The ameliorating effect of prior warm ischemia on PARP synthesis in this study may be due to a preconditioning response of the prior warm ischemia, before hypothermic ischemia and reperfusion occur. This cannot be demonstrated or ruled out; however, this seems unlikely because canine kidneys do not precondition with cycles of warm ischemia (17).…”

Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

Mangino

Ametani

Szabó

et al. 2004

American Journal of Physiology-Renal Physiology

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Mangino, Martin J., Mary Ametani, Csaba Szabó, and James H. Southard. Poly (ADP-ribose) polymerase and renal hypothermicpreservation injury. Am J Physiol Renal Physiol 286: F838-F847, 2004. First published December 23, 2003 10.1152/ajprenal. 00230.2003.-The nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been implicated in ischemia-reperfusion injury in many tissues under normothermic conditions. The purpose of this study was to determine whether PARP contributes to mechanisms of the hypothermic ischemia-reperfusion injury that occurs when kidneys are cold stored for transplantation. Cortical tissue slice PARP enzyme activity rose significantly with prolonged cold storage and was dependent on both reperfusion and preservation quality. However, prior exposure to warm ischemia abrogated this increase. PARP protein increased with cold storage but was not dependent on reperfusion. PARP enzyme activity rose quickly after reperfusion in buffer and was not different when whole blood was used. Addition of exogenous hydrogen peroxide (3 mM) to normal renal slices significantly increased PARP activity over 4 h in the cortex but not in the medulla, but the medullary basal PARP synthesis rate was five times higher than that in the cortex. However, the reactive oxygen species (ROS) inhibitors catalase (2,000 U/ml), Trolox (200 M), and DMSO (15 mM) did not reduce reperfusion-induced PARP activity in cold-stored cortical slices. Finally, PARP inhibitors potentiated preservation injury in isolated canine proximal renal tubules. In conclusion, canine renal PARP enzyme activity rises with prolonged cold storage after reperfusion and may play a protective rather than an injurious role in hypothermic preservation for transplantation. ROS are sufficient but not necessary to activate PARP under these conditions. base excision system; NAD ϩ ; energy failure; adenosine 5Ј-triphosphate; reperfusion injury; pharmacological inhibition KIDNEYS RETRIEVED FROM CADAVER donors for transplantation are preserved after harvest to attenuate the ischemic injury that occurs during the time from harvest to transplantation into the recipient. The most important preservation strategy to reduce ischemic injury is the use of simple hypothermia. Renal oxygen demand can be reduced by ϳ97% by simple hypothermia due largely to the Q10 effect (5). This strategy, however effective, is not enough to prevent preservation injury of the tissues. Hypothermia, used to reduce oxygen demand, does so in part by reducing Na-K-ATPase activity, which causes electrolyte movements down concentration gradients, resulting in dangerous cell swelling (4). Furthermore, continued hydrolysis of phosphorylated adenine nucleotides without adequate simultaneous regeneration lowers cell ATP levels and results in loss of adenine nucleotide precursor molecules at reperfusion. This leaves the cell vulnerable at reperfusion because regeneration of ATP requires adenine nucleotide precursors in the cell. To combat these unfavorable physical and chemical changes that occur during hyp...

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Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

Mangino

Ametani

Szabó

et al. 2004

American Journal of Physiology-Renal Physiology

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“…In vivo gene transfer of myr-Akt reduced infarct size by 64% and the number of apoptotic cells by 84%. Preconditioning is a well-known phenomenon by which a brief exposure to ischemia makes a tissue more tolerant to a subsequent I-R-induced insult (35). The observation that I-R may induce the activation of a powerful antiapoptotic enzyme may explain the ability of preconditioning to reduce the deleterious effect of I-R on tubular cell survival (36).…”

Section: Discussionmentioning

confidence: 99%

Ischemia-Reperfusion Induces Glomerular and Tubular Activation of Proinflammatory and Antiapoptotic Pathways

Loverre¹,

Ditonno²,

Crovace³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Ischemia-reperfusion (I-R) injury in transplanted kidney, a key pathogenic event of delayed graft function (DGF), is characterized by tubular cell apoptosis and interstitial inflammation. Akt-mammalian target of rapamycin-S6k and NF-B-inducing kinase (NIK)-NF-B axis are the two main signaling pathways regulating cell survival and inflammation. Rapamycin, an immunosuppressive drug inhibiting the Akt axis, is associated with a prolonged DGF. The aim of this study was to evaluate Akt and NF-B axis activation in patients who had DGF and received or not rapamycin and in a pig model of I-R and the role of coagulation priming in this setting. In graft biopsies from patients who were not receiving rapamycin, phosphorylated Akt increased in proximal tubular, interstitial, and mesangial cells with a clear nuclear translocation. The same pattern of activation was observed for S6k and NIK.

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“…Therefore, measurement of serum chemistry was not valuable. We found that an IPC of 5 min, completed only 10 min before the onset of sustained ischemia, renders protection against the ischemic insult in a dog model or is at least harmless as opposed to the traditional view in literature [1,9] . So it seems that brief stress or prescribing specific medications can intensify the intrinsic protective cell mechanisms from subsequent severe tissue stress [2,3] .…”

Section: Discussionmentioning

confidence: 96%

Ischemic Preconditioning Protects the Dog Kidney from Ischemia-Reperfusion Injury

et al. 2007

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Objective: To evaluate the effects of unilateral ischemic insult and ischemic preconditioning (IPC) on renal histology in a canine model. Methods: 30 dogs were randomized into 4 groups. In group A (5 male controls) and group B (5 female controls), ischemia was induced by clamping both left renal arteries for 40 min. Dogs in group C (10 male cases) or group D (10 female cases) underwent 5 min of arterial clamping and 10 min of declamping prior to the final 40-min ischemia induction. Renal biopsy was prepared 48 h later and microscopically examined. Results: The control groups (A and B) developed 40% frank necrosis, 60% moderate injury, and there was no intact renal tissue in this group with no difference between sexes. The IPC groups (C and D) revealed 55% moderate injury and 45% normal pathology; however, there was no frank necrosis among them. Better IPC protection in the female group was not statistically significant. Conclusion: An IPC schedule of 5-min ischemia and 10-min reperfusion improves ischemia-reperfusion injury from subsequent prolonged ischemia in a canine model.

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Is ischemic preconditioning of the kidney clinically relevant?

Cited by 37 publications

References 33 publications

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

Ischemia-Reperfusion Induces Glomerular and Tubular Activation of Proinflammatory and Antiapoptotic Pathways

Ischemic Preconditioning Protects the Dog Kidney from Ischemia-Reperfusion Injury

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