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Molecular Medicine

, Volume 14, Issue 7–8, pp 502–516 | Cite as

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

  • Matthieu Legrand
  • Egbert G. Mik
  • Tanja Johannes
  • Didier Payen
  • Can Ince
Review Article

Abstract

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

Notes

Acknowledgments

The authors acknowledge Richard Milstein from Skylab Industry for help with the illustration in Figure 2.

References

  1. 1.
    Brady HR, Singer GG. (1995) Acute renal failure. Lancet 346:1533–40.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Bagshaw SM. (2006) The long-term outcome after acute renal failure. Curr. Opin. Crit. Care 12:561–6.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Korkeila M, Ruokonen E, Takala J. (2000) Costs of care, long-term prognosis and quality of life in patients requiring renal replacement therapy during intensive care. Intensive Care Med. 26:1824–31.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Manns B, et al. (2003) Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery. Crit. Care Med. 31:449–55.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Bell M, Martling CR. (2007) Long-term outcome after intensive care: can we protect the kidney? Crit. Care 11:147.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Hoste EA, Kellum JA. (2006) Acute kidney injury: epidemiology and diagnostic criteria. Curr. Opin. Crit. Care 12:531–7.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Ellenberger C, et al. (2006) Incidence, risk factors and prognosis of changes in serum creatinine early after aortic abdominal surgery. Intensive Care Med. 32:1808–16.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Wong GT, Irwin MG. (2007) Contrast-induced nephropathy. Br. J. Anaesth. 99:474–83.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Eckardt KU, et al. (2005) Role of hypoxia in the pathogenesis of renal disease. Kidney Int. Suppl. S46–51.Google Scholar
  10. 10.
    Leong CL, Anderson WP, O’Connor PM, Evans RG. (2007) Evidence that renal arterial-venous oxygen shunting contributes to dynamic regulation of renal oxygenation. Am. J. Physiol. Renal Physiol. 292:F1726–33.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Janssen WM, Beekhuis H, de Bruin R, de Jong PE, de Zeeuw D. (1995) Noninvasive measurement of intrarenal blood flow distribution: kinetic model of renal 123I-hippuran handling. Am. J. Physiol. 269:F571–80.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Pallone TL, Robertson CR, Jamison RL. (1990) Renal medullary microcirculation. Physiol. Rev. 70:885–920.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Pallone TL, Silldorff EP, Turner MR. (1998) Intrarenal blood flow: microvascular anatomy and the regulation of medullary perfusion. Clin. Exp. Pharmacol. Physiol. 25:383–92.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Joo JD, et al. (2007) Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. Am. J. Physiol. Renal Physiol. 293:F1847–57.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Whitehouse T, Stotz M, Taylor V, Stidwill R, Singer M. (2006) Tissue oxygen and hemodynamics in renal medulla, cortex, and corticomedullary junction during hemorrhage-reperfusion. Am. J. Physiol. Renal Physiol. 291:F647–53.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Rosen S, Epstein FH, Brezis M. (1992) Determinants of intrarenal oxygenation: factors in acute renal failure. Ren. Fail. 14:321–5.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Cohen JJ. (1979) Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism? Am. J. Physiol. 236: F423–33.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Pallone TL, Zhang Z, Rhinehart K. (2003) Physiology of the renal medullary microcirculation. Am. J. Physiol. Renal Physiol. 284:F253–66.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Brezis M, Rosen S. (1995) Hypoxia of the renal medulla: its implications for disease. N. Engl. J. Med. 332:647–55.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Sutton TA, Mang HE, Campos SB, Sandoval RM, Yoder MC, Molitoris BA. (2003) Injury of the renal microvascular endothelium alters barrier function after ischemia. Am. J. Physiol. Renal Physiol. 285:F191–8.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Yamamoto T, et al. (2002) Intravital videomicroscopy of peritubular capillaries in renal ischemia. Am. J. Physiol. Renal Physiol. 282: F1150–5.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Horbelt M, et al. (2007) Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury. Am. J. Physiol. Renal Physiol. 293:F688–95.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Jassem W, Fuggle SV, Rela M, Koo DD, Heaton ND. (2002) The role of mitochondria in ischemia/ reperfusion injury. Transplantation 73:493–9.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Pan Y, et al. (2007) Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol. Cell. Biol. 27: 912–25.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Coremans JM, Van Aken M, Naus DC, Van Velthuysen ML, Bruining HA, Puppels GJ. (2000) Pretransplantation assessment of renal viability with NADH fluorimetry. Kidney Int. 57:671–83.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Lameire N, Van Biesen W, Vanholder R. (2005) Acute renal failure. Lancet 365:417–30.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Rosen S, Heyman SN. (2001) Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int. 60:1220–4.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Schnackenberg CG. (2002) Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282:R335–42.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Li C, Jackson RM. (2002) Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am. J. Physiol. Cell Physiol. 282:C227–41.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Schrier RW, Wang W, Poole B, Mitra A. (2004) Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J. Clin. Invest. 114:5–14.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Connett RJ, Honig CR, Gayeski TE, Brooks GA. (1990) Defining hypoxia: a systems view of VO2, glycolysis, energetics, and intracellular PO2. J. Appl. Physiol. 68:833–42.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Sutton TA, Fisher CJ, Molitoris BA. (2002) Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int. 62:1539–49.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Arendshorst WJ, Finn WF, Gottschalk CW. (1975) Pathogenesis of acute renal failure following temporary renal ischemia in the rat. Circ. Res. 37:558–68.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Olof P, Hellberg A, Kallskog O, Wolgast M. (1991) Red cell trapping and postischemic renal blood flow: differences between the cortex, outer and inner medulla. Kidney Int. 40:625–31.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Mason J, Torhorst J, Welsch J. (1984) Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure. Kidney Int. 26:283–93.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Thiel G, de Rougemont D, Kriz W, Mason J, Torhorst J, Wolgast M. (1982) The role of reduced medullary perfusion in the genesis of acute ischemic renal failure: summary of a round-table discussion. Nephron 31:321–3.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Summers WK, Jamison RL. (1971) The no reflow phenomenon in renal ischemia. Lab. Invest. 25: 635–43.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Johannes T, Mik EG, Nohe B, Raat NJ, Unertl KE, Ince C. (2006) Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia. Crit. Care 10:R88.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Johannes T, Mik EG, Ince C. (2008) Nonresuscitated endotoxemia induces microcirculatory hypoxic areas in the renal cortex in the rat. Shock. 2008, May 19 [Epub ahead of print].Google Scholar
  40. 40.
    Pallone TL, Silldorff EP. (2001) Pericyte regulation of renal medullary blood flow. Exp. Nephrol. 9: 165–70.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Molitoris BA, Sandoval R, Sutton TA. (2002) Endothelial injury and dysfunction in ischemic acute renal failure. Crit. Care Med. 30:S235–40.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Kone BC, Baylis C. (1997) Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am. J. Physiol. 272:F561–78.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Guan Z, Gobe G, Willgoss D, Endre ZH. (2006) Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide. Am. J. Physiol Renal Physiol. 291:F619–28.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Ito S, Abe K. (1997) Contractile properties of afferent and efferent arterioles. Clin. Exp. Pharmacol. Physiol 24:532–5.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Cowley AW Jr, Mori T, Mattson D, Zou AP. (2003) Role of renal NO production in the regulation of medullary blood flow. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284:R1355–69.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Wu F, Park F, Cowley AW Jr, Mattson DL. (1999) Quantification of nitric oxide synthase activity in microdissected segments of the rat kidney. Am. J. Physiol. 276:F874–81.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Arima S, Ito S. (2000) Isolated juxtaglomerular apparatus as a tool for exploring glomerular hemodynamics: application of microperfusion techniques. Exp. Nephrol. 8:304–11.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Kone BC. (1999) Localization and regulation of nitric oxide synthase isoforms in the kidney. Semin. Nephrol. 19:230–41.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Buttery LD, Evans TJ, Springall DR, Carpenter A, Cohen J, Polak JM. (1994) Immunochemical localization of inducible nitric oxide synthase in endotoxin-treated rats. Lab. Invest. 71:755–64.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Tojo A, et al. (1994) Immunocytochemical localization of distinct isoforms of nitric oxide synthase in the juxtaglomerular apparatus of normal rat kidney. J. Am. Soc. Nephrol. 4:1438–47.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Brown R, Ollerstam A, Persson AE. (2004) Neuronal nitric oxide synthase inhibition sensitizes the tubuloglomerular feedback mechanism after volume expansion. Kidney Int. 65:1349–56.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Grzelec-Mojzesowicz M, Sadowski J. (2007) Renal tissue NO and intrarenal haemodynamics during experimental variations of NO content in anaesthetised rats. J. Physiol. Pharmacol. 58:149–63.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Ito S, Carretero OA, Abe K. (1997) Role of nitric oxide in the control of glomerular microcirculation. Clin. Exp. Pharmacol. Physiol. 24:578–81.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M. (1994) Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J. Clin. Invest. 94:1069–75.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Goligorsky MS, Brodsky SV, Noiri E. (2004) NO bioavailability, endothelial dysfunction, and acute renal failure: new insights into pathophysiology. Semin. Nephrol. 24:316–23.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Gunnett CA, Lund DD, McDowell AK, Faraci FM, Heistad DD. (2005) Mechanisms of inducible nitric oxide synthase-mediated vascular dysfunction. Arterioscler. Thromb. Vasc. Biol. 25: 1617–22.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Yu L, Gengaro PE, Niederberger M, Burke TJ, Schrier RW. (1994) Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury. Proc. Natl. Acad. Sci. U. S. A. 91:1691–5.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Noiri E, Peresleni T, Miller F, Goligorsky MS. (1996) In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J. Clin. Invest. 97:2377–83.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Chatterjee PK, et al. (2002) Inhibition of inducible nitric oxide synthase reduces renal ischemia/ reperfusion injury. Kidney Int. 61:862–71.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Wangsiripaisan A, Gengaro PE, Nemenoff RA, Ling H, Edelstein CL, Schrier RW. (1999) Effect of nitric oxide donors on renal tubular epithelial cell-matrix adhesion. Kidney Int. 55:2281–8.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Schild L, Reinheckel T, Reiser M, Horn TF, Wolf G, Augustin W. (2003) Nitric oxide produced in rat liver mitochondria causes oxidative stress and impairment of respiration after transient hypoxia. FASEB J. 17:2194–201.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Brezis M, Heyman SN, Dinour D, Epstein FH, Rosen S. (1991) Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys. J. Clin. Invest. 88:390–5.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Chung AW, et al. (2004) Platelet-leukocyte aggregation induced by PAR agonists: regulation by nitric oxide and matrix metalloproteinases. Br. J. Pharmacol. 143:845–55.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Phelan MW, Faller DV. (1996) Hypoxia decreases constitutive nitric oxide synthase transcript and protein in cultured endothelial cells. J. Cell Physiol. 167:469–76.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Brodsky SV, et al. (2002) Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells. Am. J. Physiol. Renal Physiol. 282:F1140–9.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Lieberthal W, Wolf EF, Rennke HG, Valeri CR, Levinsky NG. (1989) Renal ischemia and reperfusion impair endothelium-dependent vascular relaxation. Am. J. Physiol. 256:F894–900.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Rosenberger C, Rosen S, Heyman SN. (2006) Renal parenchymal oxygenation and hypoxia adaptation in acute kidney injury. Clin. Exp. Pharmacol. Physiol. 33:980–8.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Rabelink TJ, van Zonneveld AJ. (2006) Coupling eNOS uncoupling to the innate immune response. Arterioscler. Thromb. Vasc. Biol. 26:2585–7.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Kakoki M, et al. (2000) Effects of tetrahydrobiopterin on endothelial dysfunction in rats with ischemic acute renal failure. J. Am. Soc. Nephrol. 11:301–9.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Bertuglia S, Giusti A. (2005) Role of nitric oxide in capillary perfusion and oxygen delivery regulation during systemic hypoxia. Am. J. Physiol. Heart Circ. Physiol. 288:H525–31.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Crawford JH, et al. (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107:566–74.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Heyman SN, Goldfarb M, Darmon D, Brezis M. (1999) Tissue oxygenation modifies nitric oxide bioavailability. Microcirculation 6:199–203.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Jia L, Bonaventura C, Bonaventura J, Stamler JS. (1996) S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 380:221–6.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Gladwin MT. (2006) Role of the red blood cell in nitric oxide homeostasis and hypoxic vasodilation. Adv. Exp. Med. Biol. 588:189–205.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Conger J, Robinette J, Villar A, Raij L, Shultz P. (1995) Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats. J. Clin. Invest. 96:631–8.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Jerkic M, et al. (2004) Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure. Nephrol. Dial. Transplant. 19:83–94.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Masumura H, Kunitada S, Irie K, Ashida S, Abe Y. (1991) A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury. Eur. J. Pharmacol. 193:321–7.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Klausner JM, et al. (1989) Postischemic renal injury is mediated by neutrophils and leukotrienes. Am. J. Physiol. 256:F794–802.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Conger JD, Robinette JB, Schrier RW. (1988) Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure. J. Clin. Invest. 82:532–7.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Harriman JF, Liu XL, Aleo MD, Machaca K, Schnellmann RG. (2002) Endoplasmic reticulum Ca(2+) signaling and calpains mediate renal cell death. Cell Death Differ. 9:734–41.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Kurata H, et al. (2005) Protective effect of nitric oxide on ischemia/reperfusion-induced renal injury and endothelin-1 overproduction. Eur. J. Pharmacol. 517:232–9.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Forbes JM, Hewitson TD, Becker GJ, Jones CL. (2001) Simultaneous blockade of endothelin A and B receptors in ischemic acute renal failure is detrimental to long-term kidney function. Kidney Int. 59:1333–41.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Hao CM, Breyer MD. (2007) Physiologic and pathophysiologic roles of lipid mediators in the kidney. Kidney Int. 71:1105–15.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    DiBona GF. (1986) Prostaglandins and nonsteroidal anti-inflammatory drugs: effects on renal hemodynamics. Am. J. Med. 80:12–21.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Catella-Lawson F, et al. (1999) Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J. Pharmacol. Exp. Ther. 289:735–41.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Llinas MT, Lopez R, Rodriguez F, Roig F, Salazar FJ. (2001) Role of COX-2-derived metabolites in regulation of the renal hemodynamic response to norepinephrine. Am. J. Physiol. Renal Physiol. 281:F975–82.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Rodriguez F, Llinas MT, Gonzalez JD, Rivera J, Salazar FJ. (2000) Renal changes induced by a cyclooxygenase-2 inhibitor during normal and low sodium intake. Hypertension 36:276–81.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Ling H, et al. (1998) Effect of hypoxia on proximal tubules isolated from nitric oxide synthase knockout mice. Kidney Int. 53:1642–6.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Farge D, De la Coussaye JE, Beloucif S, Fratacci MD, Payen DM. (1995) Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis. Chest 107:1095–100.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Payen DM, et al. (1987) Hemodynamic, gas exchange, and hormonal consequences of LBPP during PEEP ventilation. J. Appl. Physiol. 62: 61–70.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Imig JD. (2006) Eicosanoids and renal vascular function in diseases. Clin. Sci. (Lond.) 111:21–34.CrossRefGoogle Scholar
  92. 92.
    Lewis RA, Austen KF, Soberman RJ. (1990) Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N. Engl. J. Med. 323:645–55.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Pace-Asciak CR, Asotra S. (1989) Biosynthesis, catabolism, and biological properties of HPETEs, hydroperoxide derivatives of arachidonic acid. Free Radic. Biol. Med. 7:409–33.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN. (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–6.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Yiu SS, Zhao X, Inscho EW, Imig JD. (2003) 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels. J. Lipid Res. 44:2391–9.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Katoh T, Takahashi K, DeBoer DK, Serhan CN, Badr KF. (1992) Renal hemodynamic actions of lipoxins in rats: a comparative physiological study. Am. J. Physiol. 263:F436–42.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Kwon O, et al. (1998) Backleak, tight junctions, and cell-cell adhesion in postischemic injury to the renal allograft. J. Clin. Invest. 101:2054–64.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Leemreis JR, Versteilen AM, Sipkema P, Groeneveld AB, Musters RJ. (2006) Digital image analysis of cytoskeletal F-actin disintegration in renal microvascular endothelium following ischemia/reperfusion. Cytometry A 69:973–8.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Genesca M, Sola A, Hotter G. (2006) Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion. Apoptosis 11:563–71.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Noll T, Muhs A, Besselmann M, Watanabe H, Piper HM. (1995) Initiation of hyperpermeability in energy-depleted coronary endothelial monolayers. Am. J. Physiol. 268:H1462–70.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Kevil CG, Oshima T, Alexander B, Coe LL, Alexander JS. (2000) H(2)O(2)-mediated permeability: role of MAPK and occludin. Am. J. Physiol. Cell Physiol. 279:C21–30.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Kevil CG, Oshima T, Alexander JS. (2001) The role of p38 MAP kinase in hydrogen peroxide mediated endothelial solute permeability. Endothelium 8:107–16.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Ochoa L, Waypa G, Mahoney JR Jr, Rodriguez L, Minnear FL. (1997) Contrasting effects of hypochlorous acid and hydrogen peroxide on endothelial permeability: prevention with cAMP drugs. Am. J. Respir. Crit. Care Med. 156:1247–55.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Basile DP, Donohoe D, Roethe K, Osborn JL. (2001) Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am. J. Physiol. Renal Physiol. 281:F887–99.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Sutton TA, Horbelt M, Sandoval RM. (2006) Imaging vascular pathology. Nephron Physiol. 103:p82–5.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Dejana E. (2004) Endothelial cell-cell junctions: happy together. Nat. Rev. Mol. Cell. Biol. 5: 261–70.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Soullier S, Gayrard N, Méjean C, Swarcz I, Mourad G, Argilés A. (2005) Molecular mechanisms involved in kidney ischemia-reperfusion [in French]. Nephrol. Ther. 1:315–21.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Johnston WH, Latta H. (1977) Glomerular mesangial and endothelial cell swelling following temporary renal ischemia and its role in the no-reflow phenomenon. Am. J. Pathol. 89: 153–66.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Flores J, DiBona DR, Beck CH, Leaf A. (1972) The role of cell swelling in ischemic renal damage and the protective effect of hypertonic solute. J. Clin. Invest. 51:118–26.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Nilius B, Droogmans G. (2001) Ion channels and their functional role in vascular endothelium. Physiol. Rev. 81:1415–59.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Orie NN, Fry CH, Clapp LH. (2006) Evidence that inward rectifier K+ channels mediate relaxation by the PGI2 receptor agonist cicaprost via a cyclic AMP-independent mechanism. Cardiovasc. Res. 69:107–15.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Bychkov R, et al. (1999) Hydrogen peroxide, potassium currents, and membrane potential in human endothelial cells. Circulation 99:1719–25.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Kramer AA, Postler G, Salhab KF, Mendez C, Carey LC, Rabb H. (1999) Renal ischemia/ reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Kidney Int. 55:2362–7.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Okajima K. (2004) Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications. Curr. Vasc. Pharmacol. 2:125–33.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Peek GJ, Firmin RK. (1999) The inflammatory and coagulative response to prolonged extra-corporeal membrane oxygenation. ASAIO J. 45:250–63.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Xu XP, Pollock JS, Tanner MA, Myers PR. (1995) Hypoxia activates nitric oxide synthase and stimulates nitric oxide production in porcine coronary resistance arteriolar endothelial cells. Cardiovasc. Res. 30:841–7.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Aird WC. (2003) Endothelial cell heterogeneity. Crit. Care Med. 31:S221–30.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Stevens T, et al. (2001) NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases. Am. J. Physiol. Cell Physiol. 281: C1422–33.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Sheridan AM, Bonventre JV. (2000) Cell biology and molecular mechanisms of injury in ischemic acute renal failure. Curr. Opin. Nephrol. Hypertens. 9:427–34.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Dragun D, Haller H. (1999) Diapedesis of leukocytes: antisense oligonucleotides for rescue. Exp. Nephrol. 7:185–92.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Burne-Taney MJ, Rabb H. (2003) The role of adhesion molecules and T cells in ischemic renal injury. Curr. Opin. Nephrol. Hypertens. 12:85–90.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Savransky V, Molls RR, Burne-Taney M, Chien CC, Racusen L, Rabb H. (2006) Role of the T-cell receptor in kidney ischemia-reperfusion injury. Kidney Int. 69:233–8.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Ysebaert DK, et al. (2004) T cells as mediators in renal ischemia/reperfusion injury. Kidney Int. 66:491–6.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Friedewald JJ, Rabb H. (2004) Inflammatory cells in ischemic acute renal failure. Kidney Int. 66:486–91.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Thornton MA, Winn R, Alpers CE, Zager RA. (1989) An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury. Am. J. Pathol. 135:509–15.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Paller MS. (1989) Effect of neutrophil depletion on ischemic renal injury in the rat. J. Lab. Clin. Med. 113:379–86.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Rabb H, O’Meara YM, Maderna P, Coleman P, Brady HR. (1997) Leukocytes, cell adhesion molecules and ischemic acute renal failure. Kidney Int. 51:1463–8.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Takada M, Chandraker A, Nadeau KC, Sayegh MH, Tilney NL. (1997) The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury. J. Clin. Invest. 100:1199–203.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    De Greef KE, et al. (2001) Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia. Kidney Int. 60:1415–27.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Chandraker A, Takada M, Nadeau KC, Peach R, Tilney NL, Sayegh MH. (1997) CD28-b7 blockade in organ dysfunction secondary to cold ischemia/reperfusion injury. Kidney Int. 52:1678–84.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Rabb H, et al. (2000) Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice. Am. J. Physiol. Renal Physiol. 279:F525–31.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Bonventre JV, Weinberg JM. (2003) Recent advances in the pathophysiology of ischemic acute renal failure. J. Am. Soc. Nephrol. 14: 2199–210.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Rabb H, et al. (1994) Role of CD11a and CD11b in ischemic acute renal failure in rats. Am. J. Physiol. 267:F1052–8.PubMedPubMedCentralGoogle Scholar
  134. 134.
    Rao RM, Yang L, Garcia-Cardena G, Luscinskas FW. (2007) Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ. Res. 101:234–7.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Chiao H, Kohda Y, McLeroy P, Craig L, Housini I, Star RA. (1997) Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. J. Clin. Invest. 99:1165–72.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. (1999) Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Am. J. Physiol. 277:R922–9.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Simmons EM, et al. (2004) Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int. 65:1357–65.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Martin DR, Lewington AJ, Hammerman MR, Padanilam BJ. (2000) Inhibition of poly(ADP-ribose) polymerase attenuates ischemic renal injury in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279:R1834–40.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Chatterjee PK, Zacharowski K, Cuzzocrea S, Otto M, Thiemermann C. (2000) Inhibitors of poly (ADP-ribose) synthetase reduce renal ischemia-reperfusion injury in the anesthetized rat in vivo. FASEB J. 14:641–51.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Zheng J, Devalaraja-Narashimha K, Singaravelu K, Padanilam BJ. (2005) Poly(ADP-ribose) polymerase-1 gene ablation protects mice from ischemic renal injury. Am. J. Physiol. Renal Physiol. 288:F387–98.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Kota BP, Huang TH, Roufogalis BD. (2005) An overview on biological mechanisms of PPARs. Pharmacol. Res. 51:85–94.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Devalaraja-Narashimha K, Singaravelu K, Padanilam BJ. (2005) Poly(ADP-ribose) polymerase-mediated cell injury in acute renal failure. Pharmacol. Res. 52:44–59.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Kelly KJ, Williams WW Jr, Colvin RB, Bonventre JV. (1994) Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury. Proc. Natl. Acad. Sci. U. S. A. 91:812–6.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Molitoris BA, Marrs J. (1999) The role of cell adhesion molecules in ischemic acute renal failure. Am. J. Med. 106:583–92.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Takada M, Nadeau KC, Shaw GD, Marquette KA, Tilney NL. (1997) The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney: inhibition by a soluble P-selectin ligand. J. Clin. Invest. 99:2682–90.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Singbartl K, Forlow SB, Ley K. (2001) Platelet, but not endothelial, P-selectin is critical for neutrophil-mediated acute postischemic renal failure. FASEB J. 15:2337–44.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Jayle C, et al. (2006) Protective role of selectin ligand inhibition in a large animal model of kidney ischemia-reperfusion injury. Kidney Int. 69:1749–55.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Burne-Taney MJ, Kofler J, Yokota N, Weisfeldt M, Traystman RJ, Rabb H. (2003) Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury. Am. J. Physiol. Renal Physiol. 285:F87–94.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Lieberthal W. (1998) Biology of ischemic and toxic renal tubular cell injury: role of nitric oxide and the inflammatory response. Curr. Opin. Nephrol. Hypertens. 7:289–95.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Brezis M, Heyman SN, Epstein FH. (1994) Determinants of intrarenal oxygenation. II. Hemodynamic effects. Am. J. Physiol. 267:F1063–8.PubMedPubMedCentralGoogle Scholar
  151. 151.
    O’Connor PM, Kett MM, Anderson WP, Evans RG. (2006) Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow. Am. J. Physiol. Renal Physiol. 290: F688–94.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Brezis M, Agmon Y, Epstein FH. (1994) Determinants of intrarenal oxygenation. I. Effects of diuretics. Am. J. Physiol. 267:F1059–62.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Koivisto A, Pittner J, Froelich M, Persson AE. (1999) Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide. Kidney Int. 55:2368–75.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Varela M, Herrera M, Garvin JL. (2004) Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2 and is diminished by a high-salt diet. Am. J. Physiol. Renal Physiol. 287: F224–30.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Vinas JL, Sola A, Hotter G. (2006) Mitochondrial NOS upregulation during renal I/R causes apoptosis in a peroxynitrite-dependent manner. Kidney Int. 69:1403–9.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Moncada S, Erusalimsky JD. (2002) Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat. Rev. Mol. Cell. Biol. 3:214–20.PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Laycock SK, et al. (1998) Role of nitric oxide in the control of renal oxygen consumption and the regulation of chemical work in the kidney. Circ. Res. 82:1263–71.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Gladwin MT, et al. (2006) Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am. J. Physiol. Heart Circ. Physiol. 291:H2026–35.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Brown GC. (1995) Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase. FEBS Lett. 369: 136–9.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 160.
    Davidson SM, Duchen MR. (2006) Effects of NO on mitochondrial function in cardiomyocytes: pathophysiological relevance. Cardiovasc. Res. 71:10–21.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Boveris A, Costa LE, Poderoso JJ, Carreras MC, Cadenas E. (2000) Regulation of mitochondrial respiration by oxygen and nitric oxide. Ann. N. Y. Acad. Sci. 899:121–35.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Takehara Y, et al. (1996) Oxygen-dependent reversible inhibition of mitochondrial respiration by nitric oxide. Cell Struct. Funct. 21:251–8.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 163.
    Toledo-Pereyra LH, Lopez-Neblina F, Toledo AH. (2004) Reactive oxygen species and molecular biology of ischemia/reperfusion. Ann. Transplant. 9:81–3.PubMedPubMedCentralGoogle Scholar
  164. 164.
    Bertuglia S, Giusti A. (2005) Microvascular oxygenation and oxidative stress during postischemic reperfusion: PO2, ROS, and NO during reperfusion. Adv. Exp. Med. Biol. 566:23–9.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    RubioGayosso I, Platts SH, Duling BR. (2006) Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 290: H2247–56.CrossRefGoogle Scholar
  166. 166.
    Chandel NS, Budinger GR, Choe SH, Schumacker PT. (1997) Cellular respiration during hypoxia: role of cytochrome oxidase as the oxygen sensor in hepatocytes. J. Biol. Chem. 272: 18808–16.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Brealey D, et al. (2004) Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286:R491–7.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Adler S, et al. (2001) Endothelial nitric oxide synthase plays an essential role in regulation of renal oxygen consumption by NO. Am. J. Physiol. Renal Physiol. 280:F838–43.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Clementi E, Brown GC, Foxwell N, Moncada S. (1999) On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc. Natl. Acad. Sci. U. S. A. 96:1559–62.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Mik EG, et al. (2006) Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX. Nat. Methods 3:939–45.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Rabelink TJ, Wijewickrama DC, de Koning EJ. (2007) Peritubular endothelium: the Achilles heel of the kidney? Kidney Int. 72:926–30.PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Norman JT, Fine LG. (2006) Intrarenal oxygenation in chronic renal failure. Clin. Exp. Pharmacol. Physiol. 33:989–96.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Basile DP, Donohoe DL, Roethe K, Mattson DL. (2003) Chronic renal hypoxia after acute ischemic injury: effects of L-arginine on hypoxia and secondary damage. Am. J. Physiol. Renal Physiol. 284:F338–48.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Kang DH, Hughes J, Mazzali M, Schreiner GF, Johnson RJ. (2001) Impaired angiogenesis in the remnant kidney model: II. Vascular endothelial growth factor administration reduces renal fibrosis and stabilizes renal function. J. Am. Soc. Nephrol. 12:1448–57.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Yang J, et al. (2001) Telomerized human microvasculature is functional in vivo. Nat. Biotechnol. 19:219–24.PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    Sharples EJ, et al. (2004) Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J. Am. Soc. Nephrol. 15:2115–24.CrossRefGoogle Scholar
  177. 177.
    Ribatti D, Nico B, Crivellato E, Vacca A. (2005) Endothelial progenitor cells in health and disease. Histol. Histopathol. 20:1351–8.PubMedPubMedCentralGoogle Scholar
  178. 178.
    Basile DP. (2007) The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int. 72:151–6.PubMedCrossRefPubMedCentralGoogle Scholar
  179. 179.
    Li J, Deane JA, Campanale NV, Bertram JF, Ricardo SD. (2007) The contribution of bone marrow-derived cells to the development of renal interstitial fibrosis. Stem Cells 25:697–706.PubMedCrossRefPubMedCentralGoogle Scholar
  180. 180.
    Rosenberger C, et al. (2006) Hypoxia-inducible factors and tubular cell survival in isolated perfused kidneys. Kidney Int. 70:60–70.PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Rosenberger C, et al. (2005) Up-regulation of HIF in experimental acute renal failure: evidence for a protective transcriptional response to hypoxia. Kidney Int. 67:531–42.PubMedCrossRefPubMedCentralGoogle Scholar
  182. 182.
    Safran M, Kaelin WG Jr. (2003) HIF hydroxylation and the mammalian oxygen-sensing pathway. J. Clin. Invest. 111:779–83.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Haase VH. (2006) The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int. 69:1302–7.PubMedCrossRefPubMedCentralGoogle Scholar
  184. 184.
    Haase VH. (2006) Hypoxia-inducible factors in the kidney. Am. J. Physiol. Renal Physiol. 291: F271–81.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Mansfield KD, et al. (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 1:393–9.PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Sandau KB, Fandrey J, Brune B. (2001) Accumulation of HIF-1alpha under the influence of nitric oxide. Blood 97:1009–15.PubMedCrossRefPubMedCentralGoogle Scholar
  187. 187.
    Hagen T, Taylor CT, Lam F, Moncada S. (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 302:1975–8.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Schrijvers BF, Flyvbjerg A, De Vriese AS. (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int. 65:2003–17.PubMedCrossRefPubMedCentralGoogle Scholar
  189. 189.
    Kanellis J, et al. (2002) Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression. Kidney Int. 61: 1696–706.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    Kim YG, et al. (2000) Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy. Kidney Int. 58:2390–9.PubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Takahashi T, Morita K, Akagi R, Sassa S. (2004) Protective role of heme oxygenase-1 in renal ischemia. Antioxid. Redox. Signal. 6:867–77.PubMedPubMedCentralGoogle Scholar
  192. 192.
    Shimizu H, et al. (2000) Protective effect of heme oxygenase induction in ischemic acute renal failure. Crit. Care Med. 28:809–17.PubMedCrossRefPubMedCentralGoogle Scholar
  193. 193.
    Salom MG, et al. (2007) Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite. Am. J. Physiol. Heart Circ. Physiol. 293:H3542–9.PubMedCrossRefPubMedCentralGoogle Scholar
  194. 194.
    Aydin Z, Duijs J, Bajema IM, van Zonneveld AJ, Rabelink TJ. (2007) Erythropoietin, progenitors, and repair. Kidney Int. 72 Suppl:S16–20.CrossRefGoogle Scholar
  195. 195.
    Beleslin-Cokic BB, Cokic VP, Yu X, Weksler BB, Schechter AN, Noguchi CT. (2004) Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood 104:2073–80.PubMedCrossRefPubMedCentralGoogle Scholar
  196. 196.
    Biju MP, Akai Y, Shrimanker N, Haase VH. (2005) Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxiainduced cell death is glucose dependent. Am. J. Physiol. Renal Physiol. 289:F1217–26.PubMedCrossRefPubMedCentralGoogle Scholar
  197. 197.
    Schofield CJ, Ratcliffe PJ. (2004) Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell. Biol. 5: 343–54.PubMedCrossRefPubMedCentralGoogle Scholar
  198. 198.
    Rivers E, et al. (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N. Engl. J. Med. 345:1368–77.PubMedCrossRefPubMedCentralGoogle Scholar
  199. 199.
    Rivers EP, et al. (2007) The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit. Care Med. 35:2016–24.PubMedCrossRefPubMedCentralGoogle Scholar
  200. 200.
    Lameire NH, De Vriese AS, Vanholder R. (2003) Prevention and nondialytic treatment of acute renal failure. Curr. Opin. Crit. Care 9:481–90.PubMedCrossRefPubMedCentralGoogle Scholar
  201. 201.
    Venkataraman R, Kellum JA. (2007) Prevention of acute renal failure. Chest 131:300–8.PubMedCrossRefPubMedCentralGoogle Scholar
  202. 202.
    De Backer D, et al. (2006) The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit. Care Med. 34:403–8.PubMedCrossRefPubMedCentralGoogle Scholar
  203. 203.
    Schortgen F, et al. (2001) Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 357:911–6.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Brunkhorst FM, et al. (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N. Engl. J. Med. 358:125–39.PubMedCrossRefPubMedCentralGoogle Scholar
  205. 205.
    Yuruk K, Almac E, Ince C. (2007) Hydroxyethyl starch solutions and their effect on the microcirculation and tissue oxygenation. Transfus. Altern. Transfus. Med. 9:164–72.CrossRefGoogle Scholar
  206. 206.
    Blasco V, Leone M, Antonini F, Geissler A, Albanese J, Martin C. (2008) Comparison of the novel hydroxyethylstarch 130/0.4 and hydroxyethylstarch 200/0.6 in brain-dead donor resuscitation on renal function after transplantation. Br. J. Anaesth. 100:504–8.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Sakr Y, et al. (2006) Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit. Care Med. 34:589–97.PubMedCrossRefPubMedCentralGoogle Scholar
  208. 208.
    Faivre V, et al. (2005) Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits. Anesthesiology 103:514–21.PubMedCrossRefPubMedCentralGoogle Scholar
  209. 209.
    Albert M, Losser MR, Hayon D, Faivre V, Payen D. (2004) Systemic and renal macro- and micro-circulatory responses to arginine vasopressin in endotoxic rabbits. Crit. Care Med. 32:1891–8.PubMedCrossRefPubMedCentralGoogle Scholar
  210. 210.
    Gattinoni L, et al. (1995) Atrial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N. Engl. J. Med. 333: 1025–32.PubMedCrossRefPubMedCentralGoogle Scholar
  211. 211.
    Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N. Engl. J. Med. 330:1717–22.PubMedCrossRefPubMedCentralGoogle Scholar
  212. 212.
    Durairaj L, Schmidt GA. (2008) Fluid therapy in resuscitated sepsis: less is more. Chest 133: 252–63.PubMedCrossRefPubMedCentralGoogle Scholar
  213. 213.
    Thurau K, Boylan JW. (1976) Acute renal success: the unexpected logic of oliguria in acute renal failure. Am. J. Med. 61:308–15.PubMedCrossRefPubMedCentralGoogle Scholar
  214. 214.
    Macias WL, et al. (2005) New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Crit. Care 9 Suppl 4:S38–45.PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Bernard GR, et al. (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. 344:699–709.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Gupta A, Rhodes GJ, Berg DT, Gerlitz B, Molitoris BA, Grinnell BW. (2007) Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2. Am. J. Physiol. Renal Physiol. 293: F245–54.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    Gupta A, et al. (2007) Role of protein C in renal dysfunction after polymicrobial sepsis. J. Am. Soc. Nephrol. 18:860–7.PubMedCrossRefPubMedCentralGoogle Scholar
  218. 218.
    Dear JW, et al. (2006) Sepsis-induced organ failure is mediated by different pathways in the kidney and liver: acute renal failure is dependent on MyD88 but not renal cell apoptosis. Kidney Int. 69:832–6.PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Ventura CG, Coimbra TM, de Campos SB, de Castro I, Yu L, Seguro AC. (2002) Mycophenolate mofetil attenuates renal ischemia/reperfusion injury. J. Am. Soc. Nephrol. 13:2524–33.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Ysebaert DK, et al. (2003) Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after severe warm ischemia/ reperfusion renal injury. Kidney Int. 64:864–73.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Ricci Z, Cruz D, Ronco C. (2008) The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney Int. 73:538–46.PubMedCrossRefPubMedCentralGoogle Scholar
  222. 222.
    Bonventre JV. (2007) Diagnosis of acute kidney injury: from classic parameters to new biomarkers. Contrib. Nephrol. 156:213–9.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Matthieu Legrand
    • 1
    • 2
  • Egbert G. Mik
    • 3
  • Tanja Johannes
    • 4
  • Didier Payen
    • 2
  • Can Ince
    • 1
  1. 1.Department of Physiology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Anesthesiology and Critical Care, Lariboisière HospitalUniversity of Paris VIIParisFrance
  3. 3.Department of Anesthesiology, Erasmus Medical CenterUniversity of RotterdamRotterdamThe Netherlands
  4. 4.Department of Anesthesiology and Critical CareUniversity Hospital TuebingenTuebingenGermany

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