Cellular pathophysiology of ischemic acute kidney injury

Journal of Clinical Investigation

Volumn 121, Issue 11, 2011, Pages 4210-4221

  Bonventre, Joseph V ^a,b   Yang, Li ^c  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c PEKING UNIVERSITY FIRST HOSPITAL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; ADENOSINE; ALPHA CHEMOKINE; ANGIOTENSIN II; BETA INTEGRIN; BRADYKININ; COMPLEMENT; COMPLEMENT RECEPTOR; ENDOTHELIN; ENDOTHELIN 1; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 32; INTERLEUKIN 6; KIDNEY INJURY MOLECULE 1; LEUKOTRIENE C4; LEUKOTRIENE D4; MANNOSE RECEPTOR; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; NITRIC OXIDE; PROSTAGLANDIN H2; RANTES; TAMM HORSFALL GLYCOPROTEIN; THROMBOXANE A2; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ACUTE KIDNEY FAILURE; ADAPTIVE IMMUNITY; APOPTOSIS; B LYMPHOCYTE; CELL ACTIVITY; CELL ADHESION; CELL COMMUNICATION; CELL CYCLE ARREST; CELL DAMAGE; CELL DEATH; CELL INTERACTION; CELL POLARITY; CELL PROLIFERATION; CHRONIC KIDNEY DISEASE; COMPLEMENT SYSTEM; CYTOKINE PRODUCTION; DENDRITIC CELL; DISEASE COURSE; DNA SYNTHESIS; DOWN REGULATION; ENDOTHELIUM CELL; GENE EXPRESSION; GLOMERULUS FILTRATION RATE; HEMATOPOIETIC STEM CELL; HUMAN; INNATE IMMUNITY; ISCHEMIC PRECONDITIONING; KIDNEY BLOOD FLOW; KIDNEY DISTAL TUBULE; KIDNEY ISCHEMIA; KIDNEY PERFUSION; KIDNEY PROXIMAL TUBULE; KIDNEY TUBULE CELL; KIDNEY TUBULE DAMAGE; LEUKOCYTE ACTIVATION; LEUKOCYTE FUNCTION; LEUKOCYTE MIGRATION; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MEMBRANE PERMEABILITY; MESENCHYMAL STEM CELL; MOLECULAR INTERACTION; MONOCYTE; NEPHRITIS; NEUTROPHIL; NONHUMAN; PATHOPHYSIOLOGY; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; RENAL PROTECTION; REVIEW; SYMPATHETIC NERVE; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TH2 CELL; TISSUE REPAIR; UPREGULATION; VASOCONSTRICTION; VASODILATATION;

ACUTE KIDNEY INJURY; ANIMALS; ENDOTHELIUM, VASCULAR; HUMANS; INFLAMMATION; ISCHEMIA; ISCHEMIC PRECONDITIONING; KIDNEY; MICE; MULTIPLE ORGAN FAILURE; MUSCLE, SMOOTH, VASCULAR; RENAL CIRCULATION; SEPSIS;

EID: 80555157523     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI45161     Document Type: Review

References (149)

1. Mehta RL, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.
2. Lameire N, Van Biesen W, Vanholder R. The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol. 2006;2(7):364-377. (Pubitemid 44034187)
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3(3):844-861.
4. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16(11):3365-3370. (Pubitemid 46179340)
5. Hsu CY, McCulloch CE, Fan D, Ordonez JD, Chertow GM, Go AS. Community-based incidence of acute renal failure. Kidney Int. 2007;72(2):208-212. (Pubitemid 47067390)
6. Goldstein LB, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(2):517-584.
7. Hsu CY, Chertow GM, McCulloch CE, Fan D, Ordonez JD, Go AS. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol. 2009;4(5):891-898.
8. Ishani A, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009;20(1):223-228.
9. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53(6):961-973.
10. Liano F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int. 1996;50(3):811-818. (Pubitemid 26302669)
11. Mehta RL, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66(4):1613-1621. (Pubitemid 39298397)
12. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. New Engl J Med. 1996;334(22):1448-1460. (Pubitemid 126590563)
13. Le Dorze M, Legrand M, Payen D, Ince C. The role of the microcirculation in acute kidney injury. Curr Opin Crit Care. 2009;15(6):503-508.
14. Alejandro V, et al. Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft. J Clin Invest. 1995;95(2):820-831.
15. Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol. 2003;14(8):2199-2210. (Pubitemid 36909930)
16. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351(2):159-169.
17. Karlberg L, Norlen BJ, Ojteg G, Wolgast M. Impaired medullary circulation in postischemic acute renal failure. Acta Physiol Scand. 1983;118(1):11-17. (Pubitemid 13098946)
18. Mason J, Torhorst J, Welsch J. Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure. Kidney Int. 1984;26(3):283-293. (Pubitemid 14021699)
19. Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009;78(6):539-552.
20. Conger J. Hemodynamic factors in acute renal failure. Adv Ren Replace Ther. 1997;4(2 suppl 1):25-37. (Pubitemid 27198003)
21. Brooks DP. Role of endothelin in renal function and dysfunction. Clin Exp Pharmacol Physiol. 1996;23(4):345-348. (Pubitemid 26171573)
22. Kurata H, et al. Protective effect of nitric oxide on ischemia/reperfusion-induced renal injury and endothelin-1 overproduction. Eur J Pharmacol. 2005;517(3):232-239. (Pubitemid 40977900)
23. da Silveira KD, et al. ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats. Clin Sci (Lond). 2010;119(9):385-394.
24. Conger JD. Vascular abnormalities in the maintenance of acute renal failure. Circ Shock. 1983;11(3):235-244. (Pubitemid 14211650)
25. Kwon O, Hong SM, Ramesh G. Diminished NO generation by injured endothelium and loss of macula densa nNOS may contribute to sustained acute kidney injury after ischemia-reperfusion. Am J Physiol Renal Physiol. 2009;296(1):F25-F33.
26. Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 2004;66(2):480-485. (Pubitemid 38981982)
27. Blantz RC, Deng A, Miracle CM, Thomson SC. Regulation of kidney function and metabolism: a question of supply and demand. Trans Am Clin Climatol Assoc. 2007;118:23-43.
28. Brezis M, Rosen S. Hypoxia of the renal medulla - its implications for disease. N Engl J Med. 1995; 332(10):647-655.
29. Beeuwkes R III, Bonventre JV. Tubular organization and vascular-tubular relations in the dog kidney. Am J Physiol. 1975;229(3):695-713.
30. Bagnasco S, Good D, Balaban R, Burg M. Lactate production in isolated segments of the rat nephron. Am J Physiol. 1985;248(4 pt 2):F522-F526. (Pubitemid 15056867)
31. Basile DP. The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int. 2007;72(2):151-156. (Pubitemid 47067393)
32. Rabelink TJ, de Boer HC, van Zonneveld AJ. Endothelial activation and circulating markers of endothelial activation in kidney disease. Nat Rev Nephrol. 2010;6(7):404-414.
33. Kelly KJ, et al. Intercellular adhesion molecule-1 deficient mice are protected against renal ischemia. J Clin Invest. 1996;97(4):1056-1063. (Pubitemid 26070586)
34. Sutton TA, Mang HE, Campos SB, Sandoval RM, Yoder MC, Molitoris BA. Injury of the renal microvascular endothelium alters barrier function after ischemia. Am J Physiol Renal Physiol. 2003;285(2):F191-F198. (Pubitemid 36871191)
35. Basile DP, Fredrich K, Chelladurai B, Leonard EC, Parrish AR. Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. Am J Physiol Renal Physiol. 2008;294(4):F928-F936.
36. Kwon O, Hong SM, Sutton TA, Temm CJ. Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic acute kidney injury. Am J Physiol Renal Physiol. 2008;295(2):F351-F359.
37. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782-787.
38. Johnson GB, Brunn GJ, Platt JL. Activation of mammalian Toll-like receptors by endogenous agonists. Crit Rev Immunol. 2003;23(1-2):15-44. (Pubitemid 36875472)
39. Jang HR, Ko GJ, Wasowska BA, Rabb H. The interaction between ischemia-reperfusion and immune responses in the kidney. J Mol Med. 2009;87(9):859-864.
40. Wahl P, et al. Renal tubular epithelial expression of the costimulatory molecule B7RP-1 (inducible costimulator ligand). J Am Soc Nephrol. 2002;13(6):1517-1526. (Pubitemid 34579241)
41. Li H, Nord EP. CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK activation in proximal tubule cells. Am J Physiol Renal Physiol. 2002;282(6):F1020-F1033. (Pubitemid 34654467)
42. Deckers JG, De Haij S, van der Woude FJ, van der Kooij SW, Daha MR, van Kooten C. IL-4 and IL-13 augment cytokine- and CD40-induced RANTES production by human renal tubular epithelial cells in vitro. J Am Soc Nephrol. 1998;9(7):1187-1193. (Pubitemid 28283881)
43. Niemann-Masanek U, Mueller A, Yard BA, Waldherr R, van der Woude FJ. B7-1 (CD80) and B7-2 (CD 86) expression in human tubular epithelial cells in vivo and in vitro. Nephron. 2002;92(3):542-556.
44. Solez K, Morel-Maroger L, Sraer JD. The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore). 1979;58(5):362-376. (Pubitemid 10234879)
45. Awad AS, et al. Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney. Am J Physiol Renal Physiol. 2006;290(6):F1516-F1524. (Pubitemid 43830779)
46. Awad AS, et al. Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury. Kidney Int. 2009;75(7):689-698.
47. Jang HR, Rabb H. The innate immune response in ischemic acute kidney injury. Clin Immunol. 2009;130(1):41-50.
48. Li L, et al. The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury. Kidney Int. 2008;74(12):1526-1537.
49. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19(1):71-82. (Pubitemid 36859902)
50. Oh DJ, et al. Fractalkine receptor (CX3CR1) inhibition is protective against ischemic acute renal failure in mice. Am J Physiol Renal Physiol. 2008;294(1):F264-F271.
51. Day YJ, Huang L, Ye H, Linden J, Okusa MD. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages. Am J Physiol Renal Physiol. 2005;288(4):F722-F731. (Pubitemid 40381739)
52. Lee S, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22(2):317-326.
53. John R, Nelson PJ. Dendritic cells in the kidney. J Am Soc Nephrol. 2007;18(10):2628-2635. (Pubitemid 47531188)
54. Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol. 2008;181(9):5829-5835.
55. Linfert D, Chowdhry T, Rabb H. Lymphocytes and ischemia-reperfusion injury. Transplant Rev (Orlando). 2009;23(1):1-10.
56. 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. (Pubitemid 33107755)
57. Gandolfo MT, et al. Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury. Kidney Int. 2009;76(7):717-729.
58. Park P, Haas M, Cunningham PN, Bao L, Alexander JJ, Quigg RJ. Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes. Am J Physiol Renal Physiol. 2002;282(2):F352-F357. (Pubitemid 34654567)
59. Faubel S, et al. Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure. Transplantation. 2005;80(5):643-649. (Pubitemid 41377752)
60. Hochegger K, et al. Role of alpha/beta and gamma/delta T cells in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2007;293(3):F741-F747. (Pubitemid 47403344)
61. Savransky V, Molls RR, Burne-Taney M, Chien CC, Racusen L, Rabb H. Role of the T-cell receptor in kidney ischemia-reperfusion injury. Kidney Int. 2006;69(2):233-238. (Pubitemid 43323072)
62. Thurman JM, Lucia MS, Ljubanovic D, Holers VM. Acute tubular necrosis is characterized by activation of the alternative pathway of complement. Kidney Int. 2005;67(2):524-530. (Pubitemid 40139844)
63. Homeister JW, Lucchesi BR. Complement activation and inhibition in myocardial ischemia and reperfusion injury. Annu Rev Pharmacol Toxicol. 1994;34:17-40. (Pubitemid 24134694)
64. Sandor N, Pap D, Prechl J, Erdei A, Bajtay Z. A novel, complement-mediated way to enhance the interplay between macrophages, dendritic cells and T lymphocytes. Mol Immunol. 2009;47(2-3):438-448.
65. Farrar CA, Zhou W, Lin T, Sacks SH. Local extravascular pool of C3 is a determinant of postischemic acute renal failure. Faseb J. 2006;20(2):217-226. (Pubitemid 44933168)
66. Thurman JM, et al. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. J Clin Invest. 2006;116(2):357-368. (Pubitemid 43228352)
67. Renner B, et al. The complement inhibitors Crry and factor H are critical for preventing autologous complement activation on renal tubular epithelial cells. J. Immunol. 2010;185(5):3086-3094.
68. Thurman JM, et al. Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury. J Am Soc Nephrol. 2006;17(3):707-715.
69. Zheng X, et al. Protection of renal ischemia injury using combination gene silencing of complement 3 and caspase 3 genes. Transplantation. 2006;82(12):1781-1786. (Pubitemid 46035667)
70. Thurman JM, et al. C3a is required for the production of CXC chemokines by tubular epithelial cells after renal ischemia/reperfusion. J Immunol. 2007;178(3):1819-1828. (Pubitemid 46154654)
71. Zhou W, et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest. 2000;105(10):1363-1371. (Pubitemid 30322402)
72. Nath KA. Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int. 2006;70(3):432-443. (Pubitemid 44141569)
73. El-Achkar TM, Wu XR, Rauchman M, McCracken R, Kiefer S, Dagher PC. Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol. 2008;295(2):F534-F544.
74. Duffield JS, et al. Resolvin d series and protectin d1 mitigate acute kidney injury. J Immunol. 2006;177(9):5902-5911. (Pubitemid 44628803)
75. Leonard MO, et al. 15-Epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester, a synthetic analogue of 15-epi-lipoxin A(4), is protective in experimental ischemic acute renal failure. J Am Soc Nephrol. 2002;13(6):1657-1662. (Pubitemid 34579255)
76. Franquesa M, et al. Tubular epithelial cells transfected with hHGF counteracts monocyte chemotactic protein-1 up-regulation after hypoxia/reoxygenation insult. Transplant Proc. 2009;41(6):2069-2072.
77. Lech M, et al. Resident dendritic cells prevent postischemic acute renal failure by help of single Ig IL-1 receptor-related protein. J Immunol. 2009;183(6):4109-4118.
78. Bonventre JV, Brezis M, Siegel N, Rosen S, Portilla D, Venkatachalam M. Acute renal failure. I. Relative importance of proximal vs. distal tubular injury. Am J Physiol. 1998;275(5 pt 2):F623-F631.
79. Heyman SN, Rosenberger C, Rosen S. Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal hypoxic tubular injury debate revisited. Kidney Int. 2010;77(1):9-16.
80. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62(1):237-244. (Pubitemid 34754067)
81. Vaidya VS, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1(3):200-208. (Pubitemid 352831522)
82. Sutton TA, Molitoris BA. Mechanisms of cellular injury in ischemic acute renal failure. Semin Nephrol. 1998;18(5):490-497. (Pubitemid 28430752)
83. Gailit J, Colflesh Rabiner I, Simone J, Goligorsky MS. Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. Am J Physiol. 1993;264(1 pt 2):F149-F157. (Pubitemid 23059101)
84. Zuk A, Bonventre JV, Brown D, Matlin KS. Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney. Am J Physiol. 1998;275(3 pt 1):C711-C731.
85. Bush KT, Keller SH, Nigam SK. Genesis and reversal of the ischemic phenotype in epithelial cells. J Clin Invest. 2000;106(5):621-626.
86. Molitoris BA, Dahl R, Geerdes A. Cytoskeleton disruption and apical redistribution of proximal tubule Na+-K+-ATPase during ischemia. Am J Physiol. 1992;263(3 pt 2):F488-F495.
87. Brown D, Lee R, Bonventre JV. Redistribution of villin to proximal tubule basolateral membranes after ischemia and reperfusion. Am J Physiol. 1997;273(6 pt 2):F1003-F1012.
88. Prakash J, et al. Inhibition of renal rho kinase attenuates ischemia/reperfusion-induced injury. J Am Soc Nephrol. 2008;19(11):2086-2097.
89. Zuk A, Bonventre JV, Matlin KS. Expression of fibronectin splice variants in the postischemic rat kidney. Am J Physiol Renal Physiol. 2001;280(6):F1037-F1053.
90. Amin RP, et al. Identification of putative gene based markers of renal toxicity. Environ Health Perspect. 2004;112(4):465-479. (Pubitemid 38404558)
91. Villanueva S, Cespedes C, Vio CP. Ischemic acute renal failure induces the expression of a wide range of nephrogenic proteins. Am J Physiol Regul Integr Comp Physiol. 2006;290(4):R861-R870.
92. 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. (Pubitemid 28103282)
93. 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. (Pubitemid 40469655)
94. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:463-493. (Pubitemid 351738161)
95. Vaidya VS, et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010;28(5):478-485.
96. Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest. 2008;118(5):1657-1668. (Pubitemid 351632370)
97. Yamanishi Y, et al. TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury. J Exp Med. 2010;207(7):1501-1511.
98. Bonventre JV, Yang L. Kidney injury molecule-1. Curr Opin Crit Care. 2010;16(6):556-561.
99. Bao G, et al. Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol. 2010;6(8):602-609.
100. Mishra J, et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 2004;15(12):3073-3082. (Pubitemid 39578839)
101. Mori K, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemiareperfusion injury. J Clin Invest. 2005;115(3):610-621. (Pubitemid 40322235)
102. Chien CT, Lee PH, Chen CF, Ma MC, Lai MK, Hsu SM. De novo demonstration and co-localization of free-radical production and apoptosis formation in rat kidney subjected to ischemia/reperfusion. J Am Soc Nephrol. 2001;12(5):973-982.
103. Wang Z, et al. Induction of heat shock protein 70 inhibits ischemic renal injury. Kidney Int. 2011;79(8):861-870.
104. Kimura T, et al. Autophagy Protects the Proximal Tubule from Degeneration and Acute Ischemic Injury. J Am Soc Nephrol. 2011;22(5):902-913.
105. di Mari JF, Davis R, Safirstein RL. MAPK activation determines renal epithelial cell survival during oxidative injury. Am J Physiol. 1999;277(2 pt 2):F195-F203. (Pubitemid 29415137)
106. Gobe G, Zhang XJ, Willgoss DA, Schoch E, Hogg NA, Endre ZH. 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. (Pubitemid 30115075)
107. 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. (Pubitemid 47088318)
108. Nadasdy T, Laszik Z, Blick KE, Johnson LD, Silva FG. Proliferative activity of intrinsic cell populations in the normal human kidney. J Am Soc Nephrol. 1994;4(12):2032-2039.
109. Prescott LF. The normal urinary excretion rates of renal tubular cells, leucocytes and red blood cells. Clin Sci. 1966;31(3):425-435.
110. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest. 1994;93(5):2175-2188.
111. Bonventre JV. Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J Am Soc Nephrol. 2003;14 suppl 1:S55-S61. (Pubitemid 36687041)
112. Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest. 2003;112(1):42-49. (Pubitemid 38056374)
113. 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. (Pubitemid 36514661)
114. 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. (Pubitemid 40979713)
115. Humphreys BD, Bonventre JV. Mesenchymal stem cells in acute kidney injury. Annu Rev Med. 2008;59:311-325. (Pubitemid 351287940)
116. Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005;289(1):F31-F42. (Pubitemid 40863570)
117. Duffield JS, Bonventre JV. Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int. 2005;68(5):1956-1961. (Pubitemid 43117771)
118. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 2010;78(9):838-848.
119. Humphreys BD, et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008;2(3):284-291. (Pubitemid 351298594)
120. Abbate M, Brown D, Bonventre JV. Expression of NCAM recapitulates tubulogenic development in kidneys recovering from acute ischemia. Am J Physiol. 1999;277(3 pt 2):F454-F463. (Pubitemid 29459658)
121. Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK. Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol. 2010;298(5):F1078-F1094.
122. Duffield JS. Macrophages and immunologic inflammation of the kidney. Semin Nephrol. 2010; 30(3):234-254.
123. Ko GJ, Boo CS, Jo SK, Cho WY, Kim HK. Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury. Nephrol Dial Transplant. 2008;23(3):842-852. (Pubitemid 351767562)
124. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest. 2002;110(3):341-350. (Pubitemid 34847966)
125. Humphreys BD, et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol. 2010;176(1):85-97.
126. Kriz W, Kaissling B, Le Hir M. Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy? J Clin Invest. 2011;121(2):468-474.
127. Zeisberg M, Duffield JS. Resolved: EMT produces fibroblasts in the kidney. J Am Soc Nephrol. 2010;21(8):1247-1253.
128. Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 2010;16(5):535-543.
129. Bechtel W, et al. Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med. 2010;16(5):544-550.
130. Bonventre JV. Kidney ischemic preconditioning. Curr Opin Nephrol Hypertens. 2002;11(1):43-48. (Pubitemid 34053337)
131. Park KM, Byun JY, Kramers C, Kim JI, Huang PL, Bonventre JV. Inducible nitric oxide synthase is an important contributor to prolonged protective effects of ischemic preconditioning in the mouse kidney. J Biol Chem. 2003;278(29):27256-27266. (Pubitemid 36876883)
132. Rosenberger C, et al. Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol. 2002;13(7):1721-1732. (Pubitemid 34700596)
133. Bernhardt WM, et al. Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol. 2006;17(7):1970-1978. (Pubitemid 44036181)
134. Weidemann A, et al. HIF activation protects from acute kidney injury. J Am Soc Nephrol. 2008;19(3):486-494. (Pubitemid 351355392)
135. Kojima I, et al. Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. J Am Soc Nephrol. 2007;18(4):1218-1226. (Pubitemid 46536908)
136. Hill P, et al. Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2008;19(1):39-46.
137. Cai Z, et al. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha. Cardiovasc Res. 2008;77(3):463-470. (Pubitemid 351197653)
138. 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.
139. Park KM, Kramers C, Vayssier-Taussat M, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. J Biol Chem. 2002;277(3):2040-2049. (Pubitemid 34968786)
140. Yeh CH, Hsu SP, Yang CC, Chien CT, Wang NP. Hypoxic preconditioning reinforces HIF-alpha-dependent HSP70 signaling to reduce ischemic renal failure-induced renal tubular apoptosis and autophagy. Life Sci. 2010;86(3-4):115-123.
141. Holzen JP, et al. Influence of heme oxygenase-1 on microcirculation after kidney transplantation. J Surg Res. 2008;148(2):126-135.
142. Chok MK, et al. Renoprotective potency of heme oxygenase-1 induction in rat renal ischemia-reperfusion. Inflamm Allergy Drug Targets. 2009;8(4):252-259.
143. Kim J, Jang HS, Park KM. Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice. Am J Physiol Renal Physiol. 2010;298(1):F158- F166.
144. Hung CC, Ichimura T, Stevens JL, Bonventre JV. Protection of renal Epithelial cells against oxidative injury by endoplasmic reticulum stress preconditioning is mediated by ERK1/2 activation. J Biol Chem. 2003;278(31):29317-29326. (Pubitemid 36935848)
145. Burne-Taney MJ, Liu M, Baldwin WM, Racusen L, Rabb H. Decreased capacity of immune cells to cause tissue injury mediates kidney ischemic preconditioning. J Immunol. 2006;176(11):7015-7020. (Pubitemid 43787882)
146. Kinsey GR, Huang L, Vergis AL, Li L, Okusa MD. Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney. Kidney Int. 2010;77(9):771-780.
147. Cho WY, Choi HM, Lee SY, Kim MG, Kim HK, Jo SK. The role of Tregs and CD11c(+) macrophages/dendritic cells in ischemic preconditioning of the kidney. Kidney Int. 2010;78(10):981-992.
148. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis. 2009;204(2):334-341.
149. Walsh SR, et al. Remote ischemic preconditioning for renal and cardiac protection during endovascular aneurysm repair: a randomized controlled trial. J Endovasc Ther. 2009;16(6):680-689.