Skip to main content
SpringerLink
Log in

Pathogenesis of Acute Renal Failure

  • Reference work entry
Pediatric Nephrology

Abstract

Acute renal failure (ARF) is defined clinically as the sudden loss of renal function that may result from inadequate renal perfusion associated with a decrease in effective circulation, arterial or venous obstruction, renal cell injury, or obstruction to urine flow as occurs in obstructive uropathy. Renal cell injury, commonly termed intrinsic ARF, results from an ischemic or toxicant insult that causes acute tubular damage with accompanying loss of ability to reabsorb filtered solute. The resulting decrease in glomerular filtration rate (GFR), an invariable component of ARF, is then a successful adaptive response, since continued filtration of plasma across the glomerular basement membrane without reabsorption of the filtrate by injured renal tubules would result in massive losses of salt and water (1). Thus, the decreased GFR associated with ARF prevents severe depletion of extracellular fluid.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 369.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thurau K, Boylan JW. Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 1976;61(3):308–315.

    Article  PubMed  CAS  Google Scholar 

  2. Mehta RL, Chertow GM. Acute renal failure definitions and classification: time for change? J Am Soc Nephrol 2003;14(8):2178–2187.

    Article  PubMed  Google Scholar 

  3. American Society of Nephrology Renal Research Report. J Am Soc Nephrol 2005;16(7):1886–1903.

    Google Scholar 

  4. Hollenberg NK et al. Acute oliguric renal failure in man: Evidence for preferential renal cortical ischemia. Medicine (Baltimore) 1968;47(6):455–474.

    Article  CAS  Google Scholar 

  5. Oken DE. Acute renal failure (vasomotor nephropathy): Micropuncture studies of the pathogenetic mechanisms. Annu Rev Med 1975;26:307–319.

    Article  PubMed  CAS  Google Scholar 

  6. Stein JH, Lifschitz MD, Barnes LD. Current concepts on the pathophysiology of acute renal failure. Am J Physiol 1978;234(3):F171–F181.

    PubMed  CAS  Google Scholar 

  7. Mejia-Vilet JM et al. Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone. Am J Physiol Renal Physiol 2007;293(1):F78–F86.

    Article  PubMed  CAS  Google Scholar 

  8. Bidani AK, Churchill PC. Aminophylline ameliorates glycerol-induced acute renal failure in rats. Can J Physiol Pharmacol 1983;61(6):567–571.

    Article  PubMed  CAS  Google Scholar 

  9. Avison MJ et al. Metabolic alterations in the kidney during ischemic acute renal failure. Semin Nephrol 1989;9(1):98–101.

    PubMed  CAS  Google Scholar 

  10. Schnermann J, HomerSmith W. Award lecture. The juxtaglomerular apparatus: From anatomical peculiarity to physiological relevance. J Am Soc Nephrol 2003;14(6):1681–1694.

    Article  PubMed  Google Scholar 

  11. Lee HT et al. A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion. Am J Physiol Renal Physiol 2004;286(2):F298–F306.

    Article  PubMed  CAS  Google Scholar 

  12. Chan L et al. Effect of an endothelin-receptor antagonist on ischemic acute renal failure. Am J Physiol 1994;266(1 Pt 2):F135–F138.

    PubMed  CAS  Google Scholar 

  13. Kon V, Badr KF. Biological actions and pathophysiologic significance of endothelin in the kidney. Kidney Int 1991;40(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  14. Kon V et al. Glomerular actions of endothelin in vivo. J Clin Invest 1989;83(5):1762–1767.

    Article  PubMed  CAS  Google Scholar 

  15. Jerkic M et al. Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure. Nephrol Dial Transplant 2004;19(1):83–94.

    Article  PubMed  CAS  Google Scholar 

  16. Peer G, Blum M, Iaina A. Nitric oxide and acute renal failure. Nephron 1996;73(3):375–381.

    Article  PubMed  CAS  Google Scholar 

  17. Huang Z et al. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 1994;265(5180):1883–1885.

    Article  PubMed  CAS  Google Scholar 

  18. Noiri E et al. In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest 1996;97(10):2377–2383.

    Article  PubMed  CAS  Google Scholar 

  19. Yu L et al. Nitric oxide: A mediator in rat tubular hypoxia/reoxygenation injury. Proc Natl Acad Sci USA 1994;91(5):1691–1695.

    Article  PubMed  CAS  Google Scholar 

  20. Gaudio KM et al. Postischemic hemodynamics and recovery of renal adenosine triphosphate. Am J Physiol 1986;251(4 Pt 2):F603–F609.

    PubMed  CAS  Google Scholar 

  21. Paller MSA, Anderson RJ (eds.). Use of vasoactive agents in the therapy of acute renal failure. In Acute Renal Failure, Vol. 723. Brenner BML, Lazarus JM (ed.). Philadelphia, WB Saunders, 1983.

    Google Scholar 

  22. Finn WF, Chevalier RL. Recovery from postischemic acute renal failure in the rat Kidney Int 1979;16(2):113–123.

    Article  PubMed  CAS  Google Scholar 

  23. Lameire NH, DVA, Vanholder R. (ed.). Prevention and nondialytic treatment of acute renal failure. Curr Opin Crit Care 2003;9:481–490.

    Google Scholar 

  24. Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int 2004;66(2):480–485.

    Article  PubMed  CAS  Google Scholar 

  25. Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int 2004;66(2):486–491.

    Article  PubMed  Google Scholar 

  26. Molitoris BA, Sutton TA. Endothelial injury and dysfunction: Role in the extension phase of acute renal failure. Kidney Int 2004;66(2):496–499.

    Article  PubMed  Google Scholar 

  27. Dagher PC et al. Newly developed techniques to study and diagnose acute renal failure. J Am Soc Nephrol 2003;14(8):2188–2198.

    Article  PubMed  Google Scholar 

  28. Goligorsky MS. Whispers and shouts in the pathogenesis of acute renal ischaemia. Nephrol Dial Transplant 2005;20(2):261–266.

    Article  PubMed  Google Scholar 

  29. Kwon O, Phillips CL, Molitoris MA. Ischemia induces alterations in actin filaments in renal vascular smooth muscle cells. Am J Physiol Renal Physiol 2002;282(6):F1012–F1019.

    PubMed  CAS  Google Scholar 

  30. Sutton TA et al. Injury of the renal microvascular endothelium alters barrier function after ischemia. Am J Physiol Renal Physiol 2003;285(2):F191–F198.

    PubMed  CAS  Google Scholar 

  31. Vallet B. Bench-to-bedside review: Endothelial cell dysfunction in severe sepsis: A role in organ dysfunction? Crit Care 2003;7(2):130–138.

    Article  PubMed  Google Scholar 

  32. Yamamoto T et al. Intravital videomicroscopy of peritubular capillaries in renal ischemia. Am J Physiol Renal Physiol 2002;282(6):F1150–F1155.

    PubMed  CAS  Google Scholar 

  33. Brodsky SV et al. Endothelial dysfunction in ischemic acute renal failure: Rescue by transplanted endothelial cells. Am J Physiol Renal Physiol 2002;282(6):F1140–F1149.

    PubMed  CAS  Google Scholar 

  34. Basile DP et al. Angiostatin and matrix metalloprotease expression following ischemic acute renal failure. Am J Physiol Renal Physiol 2004;286(5):F893–F902.

    Article  PubMed  CAS  Google Scholar 

  35. Singbartl K, Ley K. Leukocyte recruitment and acute renal failure. J Mol Med 2004;82(2):91–101.

    PubMed  Google Scholar 

  36. Nemoto T et al. Small molecule selectin ligand inhibition improves outcome in ischemic acute renal failure. Kidney Int 2001;60(6):2205–2214.

    Article  PubMed  CAS  Google Scholar 

  37. Burne MJ, Rabb H. Pathophysiological contributions of fucosyltransferases in renal ischemia reperfusion injury. J Immunol 2002;169(5):2648–2652.

    PubMed  CAS  Google Scholar 

  38. Singbartl K, Forlow SB, Ley K. Platelet, but not endothelial, P-selectin is critical for neutrophil-mediated acute postischemic renal failure. FASEB J 2001;15(13):2337–2344.

    Article  PubMed  CAS  Google Scholar 

  39. Roelofs JJ et al. Tissue-type plasminogen activator modulates inflammatory responses and renal function in ischemia reperfusion injury. J Am Soc Nephrol 2006;7(1):131–140.

    Google Scholar 

  40. Lieberthal W, Nigam SK. Acute renal failure. I. Relative importance of proximal vs. distal tubular injury. Am J Physiol 1998;275(5 Pt 2):F623–F631.

    PubMed  CAS  Google Scholar 

  41. Brezis M et al. Renal ischemia: a new perspective. Kidney Int 1984;26(4):375–383.

    Article  PubMed  CAS  Google Scholar 

  42. Donohoe JF et al. Tubular leakage and obstruction after renal ischemia: Structural-functional correlations. Kidney Int 1978;13(3):208–222.

    Article  PubMed  CAS  Google Scholar 

  43. Gaudio KM et al. Accelerated cellular recovery after an ischemic renal injury. Am J Pathol 1983;112(3):338–346.

    PubMed  CAS  Google Scholar 

  44. Gaudio KM et al. Accelerated recovery of single nephron function by the postischemic infusion of ATP-MgCl2. Kidney Int 1982;22(1):13–20.

    Article  PubMed  CAS  Google Scholar 

  45. Myers BD et al. Transtubular leakage of glomerular filtrate in human acute renal failure. Am J Physiol 1979;237(4):F319–F325.

    PubMed  CAS  Google Scholar 

  46. Gailit J et al. Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. Am J Physiol 1993;264(1 Pt 2):F149–F157.

    PubMed  CAS  Google Scholar 

  47. Pennica D et al. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science 1987;236(4797):83–88.

    Article  PubMed  CAS  Google Scholar 

  48. Goligorsky MS, DiBona GF. Pathogenetic role of Arg-Gly-Asp-recognizing integrins in acute renal failure. off. Proc Natl Acad Sci USA 1993;90(12):5700–5704.

    Article  PubMed  CAS  Google Scholar 

  49. Noiri et al. Cyclic RGD peptides ameliorate ischemic acute renal failure in rats. Kidney Int 1994;46(4):1050–1058.

    Article  PubMed  CAS  Google Scholar 

  50. Siegel NJ, Devarajan P, VanWhy S. Renal cell injury: metabolic and structural alterations. Pediatr Res 1994;36(2):129–136.

    Article  PubMed  CAS  Google Scholar 

  51. Weinberg JM. The cell biology of ischemic renal injury. Kidney Int 1991;39(3):476–500.

    Article  PubMed  CAS  Google Scholar 

  52. Stromski ME et al. Chemical and functional correlates of postischemic renal ATP levels. Proc Natl Acad Sci USA 1986;83(16):6142–6145.

    Article  PubMed  CAS  Google Scholar 

  53. VanWhy SK et al. Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat. J Clin Invest 1994;94(4):1518–1523.

    Article  CAS  Google Scholar 

  54. VanWhy SK et al. Thresholds for cellular disruption and activation of the stress response in renal epithelia. Am J Physiol 1999;277(2 Pt 2):F227–F234.

    CAS  Google Scholar 

  55. Andreoli SP. Reactive oxygen molecules, oxidant injury and renal disease. Pediatr Nephrol 1991;5(6):733–742.

    Article  PubMed  CAS  Google Scholar 

  56. McKelvey TG et al. Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney. Am J Physiol 1988;254(5 Pt 1):G753–G760.

    PubMed  CAS  Google Scholar 

  57. Halliwell B, Gutteridge JMC (ed.). Iron and free radical reactions: Two aspects of antioxidant protection. Trends Biochem Sci 1986;11:372–375.

    Google Scholar 

  58. Paller MS. Hemoglobin- and myoglobin-induced acute renal failure in rats: Role of iron in nephrotoxicity. Am J Physiol 1988;255(3 Pt 2):F539–F544.

    PubMed  CAS  Google Scholar 

  59. Himmelfarb J et al. Oxidative stress is increased in critically ill patients with acute renal failure. J Am Soc Nephrol 2004;15(9):2449–2456.

    Article  PubMed  CAS  Google Scholar 

  60. Doi K et al. Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney. Kidney Int 2004;65(5):1714–1723.

    Article  PubMed  CAS  Google Scholar 

  61. Dragsten PR et al. First human studies with a high-molecular-weight iron chelator. J Lab Clin Med 2000;135(1):57–65.

    Article  PubMed  CAS  Google Scholar 

  62. DeVries B et al. Reduction of circulating redox-active iron by apotransferrin protects against renal ischemia-reperfusion injury. Transplantation 2004;77(5):669–675.

    Article  CAS  Google Scholar 

  63. Mishra J et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2004;15(12):3073–3082.

    Article  PubMed  Google Scholar 

  64. Arnold PE et al. In vitro versus in vivo mitochondrial calcium loading in ischemic acute renal failure. Am J Physiol 1985;248(6 Pt 2):F845–F850.

    PubMed  CAS  Google Scholar 

  65. Weinberg JM. Oxygen deprivation-induced injury to isolated rabbit kidney tubules. J Clin Invest 1985;76(3):1193–1208.

    Article  PubMed  CAS  Google Scholar 

  66. Kribben A et al. Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. J Clin Invest 1994;93(5):1922–1929.

    Article  PubMed  CAS  Google Scholar 

  67. Cheng CW et al. Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. Kidney Int 2005;68(6):2694–2703.

    Article  PubMed  CAS  Google Scholar 

  68. Cummings BS, McHowat J, Schnellmann RG. Phospholipase A(2)s in cell injury and death. J Pharmacol Exp Ther 2000;294(3):793–799.

    PubMed  CAS  Google Scholar 

  69. Humes HD et al. The role of free fatty acids in hypoxia-induced injury to renal proximal tubule cells. Am J Physiol 1989;256(4 Pt 2):F688–F696.

    PubMed  CAS  Google Scholar 

  70. Zager RA et al. Phospholipase A2-induced cytoprotection of proximal tubules: potential determinants and specificity for ATP depletion-mediated injury. J Am Soc Nephrol 1996;7(1):64–72.

    PubMed  CAS  Google Scholar 

  71. Chen Y et al. Lysophosphatidylcholine causes Ca2+ influx, enhanced DNA synthesis and cytotoxicity in cultured vascular smooth muscle cells. Atherosclerosis 1995;112(1):69–76.

    Article  PubMed  CAS  Google Scholar 

  72. Cummings BS, McHowat J, Schnellmann RG. Role of an endoplasmic reticulum Ca(2+)-independent phospholipase A(2) in oxidant-induced renal cell death. Am J Physiol Renal Physiol 2002;283(3):F492–F498.

    PubMed  CAS  Google Scholar 

  73. Johnson AC, Stahl A, Zager RA. Triglyceride accumulation in injured renal tubular cells: Alterations in both synthetic and catabolic pathways. Kidney Int 2005;67(6):2196–2209.

    Article  PubMed  CAS  Google Scholar 

  74. Zager RA, Kalhorn TF. Changes in free and esterified cholesterol: Hallmarks of acute renal tubular injury and acquired cytoresistance. Am J Pathol 2000;157(3):1007–1016.

    Article  PubMed  CAS  Google Scholar 

  75. Zager RA et al. Increased proximal tubular cholesterol content: Implications for cell injury and “acquired cytoresistance.” Kidney Int 1999;56(5):1788–1797.

    Article  PubMed  CAS  Google Scholar 

  76. Molitoris BA. New insights into the cell biology of ischemic acute renal failure. J Am Soc Nephrol 1991;1(12):1263–1270.

    PubMed  CAS  Google Scholar 

  77. Molitoris BA. Putting the actin cytoskeleton into perspective: Pathophysiology of ischemic alterations. Am J Physiol 1997;272(4 Pt 2):F430–F433.

    PubMed  CAS  Google Scholar 

  78. Atkinson SJ, Hosford MA, Molitoris BA. Mechanism of actin polymerization in cellular ATP depletion. J Biol Chem 2004;279(7):5194–5199.

    Article  PubMed  CAS  Google Scholar 

  79. Madara JL, Barenberg D, Carlson S. Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: Further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J Cell Biol1986;102(6): 2125–2136.

    Article  PubMed  CAS  Google Scholar 

  80. Kashgarian MVW, SK, Hildebrand F et al. (ed.). Regulation of expression and polar distribution of Na,K ATPase in renal epithelium during recovery from ischemic injury. In The Sodium Pump: Recent Developments. Kaplan PDP (ed.). New York, The Rockefeller University press, 1991, pp. 573-577.

    Google Scholar 

  81. Molitoris BA, Dahl R, Hosford M. Cellular ATP depletion induces disruption of the spectrin cytoskeletal network. Am J Physiol 1996;271(4 Pt 2):F790–F798.

    PubMed  CAS  Google Scholar 

  82. Woroniecki R et al. Dissociation of spectrin-ankyrin complex as a basis for loss of Na-K-ATPase polarity after ischemia. Am J Physiol Renal Physiol 2003;284(2):F358–F364.

    PubMed  CAS  Google Scholar 

  83. Ashworth SL et al. ADF/cofilin mediates actin cytoskeletal alterations in LLC-PK cells during ATP depletion. Am J Physiol Renal Physiol 2003;284(4):F852–F862.

    PubMed  CAS  Google Scholar 

  84. Ashworth SL et al. Ischemic injury induces ADF relocalization to the apical domain of rat proximal tubule cells. Am J Physiol Renal Physiol 2001;280(5):F886–F894.

    PubMed  CAS  Google Scholar 

  85. Ashworth SL et al. Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments. Am J Physiol Renal Physiol 2004;286(5):F988–F996.

    Article  PubMed  CAS  Google Scholar 

  86. Gopalakrishnan S et al. aPKC-PAR complex dysfunction and tight junction disassembly in renal epithelial cells during ATP depletion. Am J Physiol Cell Physiol 2007;292(3):C1094–C1102.

    Article  PubMed  CAS  Google Scholar 

  87. Racusen L. (ed). The morphologic basis of acute renal failure. The morphologic basis of acute renal failure. In Acute Renal Failure: A Companion To Brenner & Rector's The Kidney. Molitoris BA, Finn WF (eds.). Philadelphia, WB Saunders, 2001, pp. 1-12.

    Google Scholar 

  88. Levine, J.a.W.L., (eds.). Terminal pathways to cell death. In Acute Renal Failure: A Companion To Brenner & Rector's The Kidney. Molitoris BA, Finn WF (ed.). Philadelphia, WB Saunders Company, 2001, pp.30-59.

    Google Scholar 

  89. Marrs J, Gopalakrishnan S, Bacallao R (ed.). Tight junction and adherens junction dysfunction during ischemic injury. In Acute Renal Failure: A Companion To Brenner & Rector's The Kidney. Molitoris BA, Finn WF (eds.). Philadelphia, WB Saunders, 2001, pp. 132-142.

    Google Scholar 

  90. Jaffe R et al. Frequent apoptosis in human kidneys after acute renal hypoperfusion. Exp Nephrol 1997;5(5):399–403.

    PubMed  CAS  Google Scholar 

  91. Lieberthal W, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol 1998. 274(2 Pt 2):F315–F327.

    PubMed  CAS  Google Scholar 

  92. Castaneda MP et al. Activation of mitochondrial apoptotic pathways in human renal allografts after ischemiareperfusion injury. Transplantation 2003;76(1):50–54.

    Article  PubMed  CAS  Google Scholar 

  93. Safirstein RL. Acute renal failure: From renal physiology to the renal transcriptome. Kidney Int Suppl 2004;91:S62–S66.

    Article  PubMed  CAS  Google Scholar 

  94. Dong Z et al. Internucleosomal DNA cleavage triggered by plasma membrane damage during necrotic cell death. Involvement of serine but not cysteine proteases. Am J Pathol 1997;151(5):1205–1213.

    PubMed  CAS  Google Scholar 

  95. Hagar H, Ueda N, Shah SV. Endonuclease induced DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Kidney Int 1996;49(2):355–361.

    Article  PubMed  CAS  Google Scholar 

  96. Kelly KJ et al. A novel method to determine specificity and sensitivity of the TUNEL reaction in the quantitation of apoptosis. Am J Physiol Cell Physiol 2003;284(5):C1309–C1318.

    PubMed  CAS  Google Scholar 

  97. Nogae S et al. Induction of apoptosis in ischemia-reperfusion model of mouse kidney: Possible involvement of Fas. J Am Soc Nephrol 1998;9(4):620–631.

    PubMed  CAS  Google Scholar 

  98. Feldenberg LR et al. Partial ATP depletion induces Fas- and caspase-mediated apoptosis in MDCK cells. Am J Physiol 1999;276(6 Pt 2):F837–F846.

    PubMed  CAS  Google Scholar 

  99. DelRio M et al. The death domain of kidney ankyrin interacts with Fas and promotes Fas-mediated cell death in renal epithelia. J Am Soc Nephrol 2004;15(1):41–51.

    Article  Google Scholar 

  100. Hamar P et al. Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. Proc Natl Acad Sci USA 2004;101(41):14883–14888.

    Article  PubMed  CAS  Google Scholar 

  101. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281(5381):1309–1312.

    Article  PubMed  CAS  Google Scholar 

  102. Kroemer G, Dallaporta B, Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 1998;60: 619–642.

    Article  PubMed  CAS  Google Scholar 

  103. Zamzami N et al. Mitochondrial control of nuclear apoptosis. J Exp Med 1996;183(4):1533–1544.

    Article  PubMed  CAS  Google Scholar 

  104. Castedo M et al. Sequential acquisition of mitochondrial and plasma membrane alterations during early lymphocyte apoptosis. J Immunol 1996;157(2):512–521.

    PubMed  CAS  Google Scholar 

  105. Antonsson B et al. Inhibition of Bax channel-forming activity by Bcl-2. Science 1997;277(5324):370–372.

    Article  PubMed  CAS  Google Scholar 

  106. Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998;281(5381):1322–1326.

    Article  PubMed  CAS  Google Scholar 

  107. Saikumar P et al. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 1998;17(26):3401–3415.

    Article  PubMed  CAS  Google Scholar 

  108. Wei Q et al. Bid activation in kidney cells following ATP depletion in vitro and ischemia in vivo. Am J Physiol Renal Physiol 2004;286(4):F803–F809.

    Article  PubMed  CAS  Google Scholar 

  109. Dagher PC. Apoptosis in ischemic renal injury: Roles of GTP depletion and p53. Kidney Int 2004;66(2):506–509.

    Article  PubMed  CAS  Google Scholar 

  110. Wei Q et al. Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice. Am J Physiol Renal Physiol 2006;290(1):F35–F42.

    Article  PubMed  CAS  Google Scholar 

  111. Schwarz C et al. Failure of BCL-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function. Lab Invest 2002;82(7):941–948.

    PubMed  CAS  Google Scholar 

  112. Salahudeen AK et al. Involvement of the mitochondrial pathway in cold storage and rewarming-associated apoptosis of human renal proximal tubular cells. Am J Transplant 2003;3(3):273–280.

    Article  PubMed  CAS  Google Scholar 

  113. Liu X et al. Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 1996;86(1):147–157.

    Article  PubMed  CAS  Google Scholar 

  114. Zou H et al. Apaf-1, a human protein homologous to C. elegans. CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997;90(3):405–413.

    Article  PubMed  CAS  Google Scholar 

  115. Li P et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997;91(4):479–489.

    Article  PubMed  CAS  Google Scholar 

  116. Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl 2004;91:S56–S61.

    Article  PubMed  CAS  Google Scholar 

  117. Kielar ML et al. Maladaptive role of IL-6 in ischemic acute renal failure. J Am Soc Nephrol 2005;16(11):3315–3325.

    Article  PubMed  CAS  Google Scholar 

  118. Leemans JC et al. Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J Clin Invest 2005;115(10):2894–2903.

    Article  PubMed  CAS  Google Scholar 

  119. Gould SE et al. BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. Kidney Int 2002;61(1):51–60.

    Article  PubMed  CAS  Google Scholar 

  120. Simmons EM et al. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int 2004;65(4):1357–1365.

    Article  PubMed  CAS  Google Scholar 

  121. Hu H et al. Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction. Am J Transplant 2004;4(3):432–437.

    Article  PubMed  CAS  Google Scholar 

  122. Cao CC et al. In vivo transfection of NF-kappaB decoy oligodeoxynucleotides attenuate renal ischemia/reperfusion injury in rats. Kidney Int 2004;65(3):834–845.

    Article  PubMed  CAS  Google Scholar 

  123. Day YJ et al. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: Role of macrophages. Am J Physiol Renal Physiol 2005;288(4):F722–F731.

    Article  PubMed  CAS  Google Scholar 

  124. Ysebaert DK et al. T cells as mediators in renal ischemia/reperfusion injury. Kidney Int 2004;66(2):491–496.

    Article  PubMed  CAS  Google Scholar 

  125. Rabb H et al. Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice. Am J Physiol Renal Physiol 2000;279(3):F525–F531.

    PubMed  CAS  Google Scholar 

  126. Yokota N et al. Protective effect of T cell depletion in murine renal ischemia-reperfusion injury. Transplantation 2002;74(6):759–763.

    Article  PubMed  CAS  Google Scholar 

  127. Burne MJ et al. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure. J Clin Invest 2001;108(9):1283–1290.

    PubMed  CAS  Google Scholar 

  128. Park P et al. Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes. Am J Physiol Renal Physiol 2002;282(2):F352–F357.

    PubMed  Google Scholar 

  129. Faubel S et al. Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure. Transplantation 2005;80(5): 643–649.

    Article  PubMed  Google Scholar 

  130. Yokota N et al. Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 2003;285(2):F319–F325.

    PubMed  CAS  Google Scholar 

  131. Burne-Taney MJ et al. B cell deficiency confers protection from renal ischemia reperfusion injury. J Immunol 2003;171(6):3210–3215.

    PubMed  CAS  Google Scholar 

  132. Thurman JM et al. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol 2003;70(3):1517–1523.

    Google Scholar 

  133. Thurman JM et al. Acute tubular necrosis is characterized by activation of the alternative pathway of complement. Kidney Int 2005;67(2):524–530.

    Article  PubMed  CAS  Google Scholar 

  134. DeVries B et al. The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury. Am J Pathol 2004;165(5):1677–1688.

    Article  CAS  Google Scholar 

  135. Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol 2005;23:821–852.

    Article  PubMed  CAS  Google Scholar 

  136. Fayyazi A et al. The C5a receptor is expressed in normal renal proximal tubular but not in normal pulmonary or hepatic epithelial cells. Immunology 2000;99(1):38–45.

    Article  PubMed  CAS  Google Scholar 

  137. DeVries B et al. Complement factor C5a mediates renal ischemia-reperfusion injury independent from neutrophils. J Immunol 2003;170(7):3883–3889.

    CAS  Google Scholar 

  138. Riedemann NC et al. Increased C5a receptor expression in sepsis. J Clin Invest 2002;10(1):101–108.

    Google Scholar 

  139. De Vries B et al. Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: Inhibition of late apoptosis and inflammation. Transplantation 2003;75(3):375–382.

    Article  PubMed  CAS  Google Scholar 

  140. Arumugam TV et al. A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats. Kidney Int 2003;63(1):134–142.

    Article  PubMed  CAS  Google Scholar 

  141. Deng J et al. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 2001;60(6):2118–28.

    Article  PubMed  CAS  Google Scholar 

  142. Patel NS et al. Endogenous interleukin-6 enhances the renal injury, dysfunction, and inflammation caused by ischemia/reperfusion. J Pharmacol Exp Ther 2005;312(3):1170–1178.

    Article  PubMed  CAS  Google Scholar 

  143. Vesey DA et al. Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant 2004;19(2):348–355.

    Article  PubMed  CAS  Google Scholar 

  144. Spandou E et al. Erythropoietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model. Nephrol Dial Transplant 2006;21(2):330–336.

    Article  PubMed  CAS  Google Scholar 

  145. Langer R et al. Selectin inhibitor bimosiamose prolongs survival of kidney allografts by reduction in intragraft production of cytokines and chemokines. J Am Soc Nephrol 2004;15(11):2893–2901.

    Article  PubMed  CAS  Google Scholar 

  146. Gueler F et al. Postischemic acute renal failure is reduced by short-term statin treatment in a rat model. J Am Soc Nephrol 2002;13(9):2288–2298.

    Article  PubMed  CAS  Google Scholar 

  147. Sabbatini M et al. Atorvastatin improves the course of ischemic acute renal failure in aging rats. J Am Soc Nephrol 2004;15(4):901–909.

    Article  PubMed  CAS  Google Scholar 

  148. Gong H et al. EPO and alpha-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs and sodium transporters in rat kidney. Kidney Int 2004;66(2):683–695.

    Article  PubMed  CAS  Google Scholar 

  149. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet 2005;365(9457):417–430.

    PubMed  CAS  Google Scholar 

  150. Williams DM et al. Acute kidney failure: A pediatric experience over 20 years. Arch Pediatr Adolesc Med 2002;156(9):893–900.

    PubMed  Google Scholar 

  151. Dittrich S et al. Circulatory arrest and renal function in open-heart surgery on infants. Pediatr Cardiol 2002;23(1):15–9.

    Article  PubMed  CAS  Google Scholar 

  152. Morris MC et al. Risk factors for mortality in 137 pediatric cardiac intensive care unit patients managed with extrcorporeal membrane oxygenation. Crit Care Med 2004;32(4):1061–1069.

    Article  PubMed  Google Scholar 

  153. Goldstein SL. Pediatric acute renal failure: demographics and treatment. Contrib Nephrol 2004;144:284–290.

    Article  PubMed  Google Scholar 

  154. Kelly KJ. Acute renal failure: Much more than a kidney disease. Semin Nephrol 2006;26(2):105–113.

    Article  PubMed  CAS  Google Scholar 

  155. Hassoun HT et al. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol 2007;293(1):F30–F40.

    Article  PubMed  CAS  Google Scholar 

  156. Grigoryev DN et al. The local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol 2008;19(3):547–558.

    Article  PubMed  CAS  Google Scholar 

  157. Deng J et al. Alpha-melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion. Am J Respir Crit Care Med 2004;169(6):749–756.

    Article  PubMed  Google Scholar 

  158. Basile DP et al. Resistance to ischemic acute renal failure in the Brown Norway rat: A new model to study cytoprotection. Kidney Int 2004;65(6):2201–2211.

    Article  PubMed  CAS  Google Scholar 

  159. Vasarhelyi B et al. Genetic polymorphisms and risk for acute renal failure in preterm neonates. Pediatr Nephrol 2005;20(2):132–135.

    Article  PubMed  Google Scholar 

  160. Fekete A et al. Association between heat shock protein 72 gene polymorphism and acute renal failure in premature neonates. Pediatr Res 2003;54(4):452–455.

    Article  PubMed  CAS  Google Scholar 

  161. Nobilis A et al. Variance of ACE and AT1 receptor gene does not influence the risk of neonatal acute renal failure. Pediatr Nephrol 2001;16(12):1063–1066.

    Article  PubMed  CAS  Google Scholar 

  162. Treszl A et al. Interleukin genetic variants and the risk of renal failure in infants with infection. Pediatr Nephrol 2002;17(9):713–717.

    Article  PubMed  Google Scholar 

  163. Jaber BL et al. Cytokine gene promoter polymorphisms and mortality in acute renal failure. Cytokine 2004;25(5):212–219.

    Article  PubMed  CAS  Google Scholar 

  164. Devarajan P et al. Gene expression in early ischemic renal injury: Clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab 2003;80(4):365–376.

    Article  PubMed  CAS  Google Scholar 

  165. Kurella M et al. DNA microarray analysis of complex biologic processes. J Am Soc Nephrol. 2001;12(5):1072–1078.

    PubMed  CAS  Google Scholar 

  166. Higgins JP et al. Gene expression in the normal adult human kidney assessed by complementary DNA microarray. Mol Biol Cell 2004;15(2):649–656.

    Article  PubMed  CAS  Google Scholar 

  167. Schwab K et al. A catalogue of gene expression in the developing kidney. Kidney Int 2003;64(5):1588–1604.

    Article  PubMed  CAS  Google Scholar 

  168. Liang M et al. Transcriptome analysis and kidney research: Toward systems biology. Kidney Int 2005;67(6):2114–2122.

    Article  PubMed  Google Scholar 

  169. Thakar CV et al. Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia. J Clin Invest 2005;115(12):3451–3459.

    Article  PubMed  CAS  Google Scholar 

  170. Ichimura T et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273(7):4135–4142.

    Article  PubMed  CAS  Google Scholar 

  171. Han WK et al. Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int 2002;62(1):237–244.

    Article  PubMed  CAS  Google Scholar 

  172. Bailly V et al. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem 2002;277(42):39739–39748.

    Article  PubMed  CAS  Google Scholar 

  173. Vaidya VS et al. Urinary kidney injury molecule-1: A sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006;290(2):F517–F529.

    Article  PubMed  CAS  Google Scholar 

  174. Mishra J et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003;14(10):2534–2543.

    Article  PubMed  CAS  Google Scholar 

  175. Supavekin S et al. Differential gene expression following early renal ischemia/reperfusion. Kidney Int 2003;63(5):1714–1724.

    Article  PubMed  CAS  Google Scholar 

  176. Mishra J et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 2006;21(6):856–863.

    Article  PubMed  Google Scholar 

  177. Mishra J et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365(9466):1231–1238.

    Article  PubMed  CAS  Google Scholar 

  178. Lavery AP et al. Urinary NGAL in premature infants. Pediatr Res 2008.

    Google Scholar 

  179. Wheeler DS et al. Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008;36(4):1297–1303.

    Article  PubMed  CAS  Google Scholar 

  180. Bennett M et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study. Clin J Am Soc Nephrol 2008;3(3):665–673.

    Article  PubMed  CAS  Google Scholar 

  181. Mori K et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005;115(3):610–621.

    PubMed  CAS  Google Scholar 

  182. Akagi R, Takahashi T, Sassa S. Cytoprotective effects of heme oxygenase in acute renal failure. Contrib Nephrol 2005;148:70–85.

    Article  PubMed  CAS  Google Scholar 

  183. Gueler F et al. Long-term effects of acute ischemia and reperfusion injury. Kidney Int 2004;66(2):523–527.

    Article  PubMed  Google Scholar 

  184. Sikorski EM et al. The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury. Am J Physiol Renal Physiol 2004;286(3):F425–F441.

    Article  PubMed  CAS  Google Scholar 

  185. Tarabishi R et al. Induction of Zf9 in the kidney following early ischemia/reperfusion. Kidney Int 2005;68(4):1511–1519.

    Article  PubMed  CAS  Google Scholar 

  186. Basile DP et al. Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure. Am J Physiol Renal Physiol 2005;288(5):F953–F963.

    Article  PubMed  CAS  Google Scholar 

  187. Fujigaki Y et al. Kinetics and characterization of initially regenerating proximal tubules in S3 segment in response to various degrees of acute tubular injury. Nephrol Dial Transplant 2006;21(1):41–50.

    Article  PubMed  CAS  Google Scholar 

  188. Bonventre JV. Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J Am Soc Nephrol 2003;14(Suppl 1):S55–S61.

    Article  PubMed  Google Scholar 

  189. Gobe GC, Johnson DW. Distal tubular epithelial cells of the kidney: Potential support for proximal tubular cell survival after renal injury. Int J Biochem Cell Biol 2007;39(9):1551–1561.

    Article  PubMed  CAS  Google Scholar 

  190. Nover L. 1991, Heat Shock Response. CRC press, Boca Raton, FL, pp.573–577.

    Google Scholar 

  191. Emami A, Schwartz JH, Borkan SC. Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol 1991;260(4 Pt 2):F479–F485.

    PubMed  CAS  Google Scholar 

  192. VanWhy SK et al. Induction and intracellular localization of HSP-72 after renal ischemia. Am J Physiol 1992;263(5 Pt 2):F769–F75.

    CAS  Google Scholar 

  193. VanWhy SK et al. Expression and molecular regulation of Na+-K+-ATPase after renal ischemia. Am J Physiol 1994;267(1 Pt 2):F75–F85.

    CAS  Google Scholar 

  194. Aufricht C et al. ATP releases HSP-72 from protein aggregates after renal ischemia. Am J Physiol 1998;274(2 Pt 2):F268–F274.

    PubMed  CAS  Google Scholar 

  195. Riordan M et al. HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells. Am J Physiol Renal Physiol 2005;288(6):F1236–F1242.

    Article  PubMed  CAS  Google Scholar 

  196. Aufricht C et al. Heat-shock protein 25 induction and redistribution during actin reorganization after renal ischemia. Am J Physiol 1998;274(1 Pt 2):F215–F222.

    PubMed  CAS  Google Scholar 

  197. VanWhy SK et al. Hsp27 associates with actin and limits injury in energy depleted renal epithelia. J Am Soc Nephrol 2003;14(1):98–106.

    Article  Google Scholar 

  198. Aufricht C et al. Ischemic conditioning prevents Na,K-ATPase dissociation from the cytoskeletal cellular fraction after repeat renal ischemia in rats. Pediatr Res 2002;51(6):722–727.

    Article  PubMed  CAS  Google Scholar 

  199. Van Why, S.K.a.N.J.S., (ed.). Heat shock proteins: Role in prevention and recovery from acute renal failure. In Acute Renal Fauilre: A Companion To Brenner & Rector's The Kidney. Molitoris BA, Finn WF (eds.). Philadelphia, WB Saunders, 2001, pp. 143-156.

    Google Scholar 

  200. Mao H et al. Hsp72 inhibits focal adhesion kinase degradation in ATP-depleted renal epithelial cells. J Biol Chem 2003;278(20):18214–18220.

    Article  PubMed  CAS  Google Scholar 

  201. Turman MA, Rosenfeld SL. Heat shock protein 70 overexpression protects LLC-PK1 tubular cells from heat shock but not hypoxia. Kidney Int 1999;55(1):189–197.

    Article  PubMed  CAS  Google Scholar 

  202. Joannidis M et al. Induction of heat-shock proteins does not prevent renal tubular injury following ischemia. Kidney Int 1995;47(6):1752–1759.

    Article  PubMed  CAS  Google Scholar 

  203. Zager RA et al. Post-ischemic acute renal failure protects proximal tubules from O2 deprivation injury, possibly by inducing uremia. Kidney Int, 1994;5(6):1760–1708.

    Article  Google Scholar 

  204. Kelly KJ, Baird NR, Greene AL. Induction of stress response proteins and experimental renal ischemia/reperfusion. Kidney Int 2001;59(5):1798–1802.

    Article  PubMed  CAS  Google Scholar 

  205. Ling H et al. Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am J Physiol 1999;277(3 Pt 2):F383–F390.

    PubMed  CAS  Google Scholar 

  206. Park KM, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 2001;276(15):11870–11876.

    Article  PubMed  CAS  Google Scholar 

  207. Gaudio KM et al. Role of heat stress response in the tolerance of immature renal tubules to anoxia. Am J Physiol 1998;274(6 Pt 2):F1029–F1036.

    PubMed  CAS  Google Scholar 

  208. Vicencio A et al. Developmental expression of HSP-72 and ischemic tolerance of the immature kidney. Pediatr Nephrol 2003;18(2):85–91.

    PubMed  Google Scholar 

  209. Sreedharan R et al. Reduced tolerance of immature renal tubules to anoxia by HSF-1 decoy. Am J Physiol Renal Physiol 2005;288(2):F322–F326.

    Article  PubMed  CAS  Google Scholar 

  210. Soifer NE et al. Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia. J Clin Invest, 1993;92(6):2850–2857.

    Article  PubMed  CAS  Google Scholar 

  211. Ichimura T, Bonventre JV. 2001, Growth factors, signaling, and renal injury and repair, in acute renal failure: A companion to Brenner and Rector’s The Kidney, 6th edn. Bruce Molitoris WFF (ed.). Elsevier Health Sciences, Philadelphia, pp. 101–118.

    Google Scholar 

  212. Gobe G et al. Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat. J Am Soc Nephrol 2000;11(3):454–467.

    PubMed  CAS  Google Scholar 

  213. Tanaka H et al. Expression and function of Ets-1 during experimental acute renal failure in rats. J Am Soc Nephrol 2004;15(12):3083–3092.

    Article  PubMed  Google Scholar 

  214. Terada Y et al. Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats. J Am Soc Nephrol 2003.14(5):1223–1233.

    Article  PubMed  CAS  Google Scholar 

  215. Villanueva S et al. bFGF induces an earlier expression of nephrogenic proteins after ischemic acute renal failure. Am J Physiol Regul Integr Comp Physiol 2006;291(6):R1677–R1687.

    Article  PubMed  CAS  Google Scholar 

  216. Sharples EJ et al. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol 2004. 15(8):2115–2124.

    Article  PubMed  CAS  Google Scholar 

  217. Fiaschi-Taesch NM et al. Prevention of acute ischemic renal failure by targeted delivery of growth factors to the proximal tubule in transgenic mice: The efficacy of parathyroid hormone-related protein and hepatocyte growth factor. J Am Soc Nephrol 2004;15(1):112–125.

    Article  PubMed  CAS  Google Scholar 

  218. Cantley LG. Adult stem cells in the repair of the injured renal tubule. Nat Pract Nephrol Clin 2005;1(1):22–32.

    Article  CAS  Google Scholar 

  219. Krause DS et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 2001;105(3):369–377.

    Article  PubMed  CAS  Google Scholar 

  220. Lagasse E et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000. 6(11):1229–34.

    Article  PubMed  CAS  Google Scholar 

  221. Ianus A et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003;111(6):843–850.

    PubMed  CAS  Google Scholar 

  222. Reyes M et al. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 2002;109(3):337–346.

    PubMed  CAS  Google Scholar 

  223. Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood 2003;102(10):3483–3493.

    Article  PubMed  CAS  Google Scholar 

  224. Wagers AJ et al. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002;297(5590):2256–2259.

    Article  PubMed  CAS  Google Scholar 

  225. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004; 116(5):639–648.

    Article  PubMed  CAS  Google Scholar 

  226. Gupta S et al. A role for extrarenal cells in the regeneration following acute renal failure. Kidney Int 2002;62(4):1285–1290.

    Article  PubMed  Google Scholar 

  227. Poulsom R et al. Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 2001;195(2):229–235.

    Article  PubMed  CAS  Google Scholar 

  228. Fang TC. et al. Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury. J Am Soc Nephrol 2005;16(6):1723–1732.

    Article  PubMed  CAS  Google Scholar 

  229. Lin F, Moran A, Igarashi P. Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 2005;115(7):1756–1764.

    Article  PubMed  CAS  Google Scholar 

  230. Duffield JS et al. Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 2005;115(7):1743–1755.

    Article  PubMed  CAS  Google Scholar 

  231. Kale S et al. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 2003;112(1):42–49.

    PubMed  CAS  Google Scholar 

  232. Lin F et al. Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 2003;14(5):1188–1199.

    Article  PubMed  Google Scholar 

  233. Morigi M et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol 2004;15(7):1794–1804.

    Article  PubMed  Google Scholar 

  234. Herrera MB et al. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 2004;14(6):1035–1041.

    PubMed  Google Scholar 

  235. Togel F et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol 2005;289(1):F31–F42.

    Article  PubMed  CAS  Google Scholar 

  236. Togel F et al. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol 2007;292(5):F1626–F1635.

    Article  PubMed  CAS  Google Scholar 

  237. Stokman G et al. Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution. J Am Soc Nephrol, 2005;16(6):1684–1692.

    Article  PubMed  CAS  Google Scholar 

  238. Iwasaki M et al. Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF. J Am Soc Nephrol 2005;16(3):658–666.

    Article  PubMed  CAS  Google Scholar 

  239. Vainio S, Muller U. Inductive tissue interactions, cell signaling, and the control of kidney organogenesis. Cell 1997;90(6):975–978.

    Article  PubMed  CAS  Google Scholar 

  240. Oliver JA et al. The renal papilla is a niche for adult kidney stem cells. J Clin Invest 2004;114(6):795–804.

    PubMed  CAS  Google Scholar 

  241. Bussolati B et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol 2005;166(2):545–555.

    Article  PubMed  CAS  Google Scholar 

  242. Short B et al. Mesenchymal stem cells. Arch Med Res 2003;34(6):565–571.

    Article  PubMed  CAS  Google Scholar 

  243. Goodell MA et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996;183(4):1797–1806.

    Article  PubMed  CAS  Google Scholar 

  244. Hishikawa K et al. Musculin/MyoR is expressed in kidney side population cells and can regulate their function. J Cell Biol 2005;169(6):921–928.

    Article  PubMed  CAS  Google Scholar 

  245. Briggs JD et al. Renal function after acute tubular necrosis. Br Med J 1967;3(5564):513–516.

    Article  PubMed  CAS  Google Scholar 

  246. Lewers DT et al. Long-term follow-up of renal function and histology after acute tubular necrosis. Ann Intern Med 1970;73(4):523–529.

    PubMed  CAS  Google Scholar 

  247. Bonomini V, Stefoni S, Vangelista A. Long-term patient and renal prognosis in acute renal failure Nephron 1984;36(3):169–172.

    Article  PubMed  CAS  Google Scholar 

  248. Lowe KG. The late prognosis in acute tubular necrosis; an interim follow-up report on 14 patients. Lancet 1952;1(6718):1086–1088.

    Article  PubMed  CAS  Google Scholar 

  249. Finkenstaedt JT, Merrill JP. Renal function after recovery from acute renal failure. N Engl J Med 1956;254(22):1023–1026.

    Article  PubMed  CAS  Google Scholar 

  250. Alon US. Neonatal acute renal failure: the need for long-term follow-up . Clin Pediatr (Phila)1998;37(6):387–389.

    Article  CAS  Google Scholar 

  251. Polito C, Papale MR, La Manna A. Long-term prognosis of acute renal failure in the full-term neonate. Clin Pediatr (Phila) 1998;37(6):381–385.

    Article  CAS  Google Scholar 

  252. Shaw NJ et al. Long-term outcome for children with acute renal failure following cardiac surgery. Int J Cardiol 1991;31(2):161–165.

    Article  PubMed  CAS  Google Scholar 

  253. Askenazi DJ et al. 3–5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int 2006;69(1):184–189.

    Article  PubMed  CAS  Google Scholar 

  254. Pagtalunan ME et al. Late consequences of acute ischemic injury to a solitary kidney. J Am Soc Nephrol 1999;10(2):366–373.

    PubMed  CAS  Google Scholar 

  255. Pagtalunan ME, Olson JL, Meyer TW. Contribution of angiotensin II to late renal injury after acute ischemia. J Am Soc Nephrol 2000;11(7):1278–1286.

    PubMed  CAS  Google Scholar 

  256. Chandraker A et al. CD28-b7 blockade in organ dysfunction secondary to cold ischemia/reperfusion injury. Kidney Int 1997; 52(6):1678–1684.

    Article  PubMed  CAS  Google Scholar 

  257. Basile DP. The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int 2007;72(2):151–156.

    Article  PubMed  CAS  Google Scholar 

  258. Basile DP et al. Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol 2001;281(5):F887–F899.

    PubMed  CAS  Google Scholar 

  259. Basile DP et al. Chronic renal hypoxia after acute ischemic injury: Effects of L-arginine on hypoxia and secondary damage. Am J Physiol Renal Physio, 2003;284(2):F338–F348.

    CAS  Google Scholar 

  260. Djamali A et al. BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction. Am J Physiol Renal Physiol 2007;292(2):F513–F522.

    Article  PubMed  CAS  Google Scholar 

  261. Spurgeon KR, Donohoe DL, Basile DP. Transforming growth factor-beta in acute renal failure: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury. Am J Physiol Renal Physiol 2005;288(3):F568–F577.

    Article  PubMed  CAS  Google Scholar 

  262. Choi ME, Ballermann BJ. Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. J Biol Chem 1995;270(36):21144–21150.

    Article  PubMed  CAS  Google Scholar 

  263. O’Riordan E et al. Chronic NOS inhibition actuates endothelial-mesenchymal transformation. Am J Physiol Heart Circ Physiol 2007;292(1):H285–H294.

    Article  PubMed  CAS  Google Scholar 

  264. Norman JT, Fine LG. Intrarenal oxygenation in chronic renal failure. Clin Exp Pharmacol Physiol 2006;33(10):989–996.

    Article  PubMed  CAS  Google Scholar 

  265. Lieberthal W, Levine JS. Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury. Am J Physiol 1996;271(3 Pt 2):F477–F488.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors, separately and together, are profoundly indebted to Norman Siegel (1943–2006), a good friend who formed our careers, understanding of medicine and nephrology, and thoughts on this particular topic.

Authors
  1. Rajasree Sreedharan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prasad Devarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott K. Van Why
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Wisconsin, Wisconsin, USA

    Ellis Avner (Director, Children's Research Institute, CHHS, Associate Dean for Research, Professor of Pediatrics and Physiology) (Director, Children's Research Institute, CHHS, Associate Dean for Research, Professor of Pediatrics and Physiology)

  2. Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    William Harmon (Professor of Pediatrics, Director, Pediatric Nephrology) (Professor of Pediatrics, Director, Pediatric Nephrology)

  3. Service de Néphrologie Pédiatrique Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Hôpital Necker‐Enfants Malades, 149, rue de Sèvres, 75743, Paris Cedex 15, France

    Patrick Niaudet

  4. Department of Pediatrics Wakayama Medical University, Wakayama Medical University Hospital, 641–8510811–1, Kimiidera, Wakayama City, Japan

    Norishige Yoshikawa (Professor and Chair Pediatrician‐in‐Chief) (Professor and Chair Pediatrician‐in‐Chief)

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Sreedharan, R., Devarajan, P., Van Why, S.K. (2009). Pathogenesis of Acute Renal Failure. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76341-3_64

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-76341-3_64

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-76327-7

  • Online ISBN: 978-3-540-76341-3

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation