Advertisement

Tubular Physiology in Acute Kidney Injury: Cell Signalling, Injury and Inflammation

  • David A. Ferenbach
  • Eoin D. O’Sullivan
  • Joseph V. Bonventre
Chapter

Abstract

Acute kidney injury in man results from a diverse range of initiating insults including sepsis, drug nephrotoxicity and hypoperfusion, which generate cellular injury, inflammation and organ dysfunction. This chapter examines components of the tubular physiology of relevance to the initiation, propagation and eventual adaptive or maladaptive recovery of acute kidney injury. The effects of changes in cell polarity and cell-to-cell signalling in acute kidney injury will both be summarised, along with a discussion of the roles played by the anti-inflammatory enzyme heme oxygenase-1 and cytokine release from growth-arrested, injured or necrotic cells. The roles of leukocyte subsets, activation of toll-like receptors and complement activation in mediating inflammatory activation, tissue damage and eventual repair in the injured kidney will also be explored.

Keywords

Acute kidney injury Inflammation Heme oxygenase Leukocyte Cell signalling Cell polarity Cytokines 

Notes

Acknowledgements

DAF is funded by Intermediate Clinical Fellowship 100171MA from the Wellcome Trust. JVB is funded by grants DK039773 and DK072381 from the NIH.

References

  1. 1.
    Epstein FH, Fish EM, Molitoris BA. Alterations in epithelial polarity and the pathogenesis of disease states. N Engl J Med. 1994;330:1580–8.CrossRefGoogle Scholar
  2. 2.
    Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. 1996;334:1448–60.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Alejandro VSJ, Nelson WJ, Huie P, Sibley RK, Dafoe D, Kuo P, et al. Postischemic injury, delayed function and Na+/K+-ATPase distribution in the transplanted kidney. Kidney Int. 1995;48:1308–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Bonventre JV. Mechanisms of ischemic acute renal failure. Kidney Int. 1993;43:1160–78.CrossRefPubMedGoogle Scholar
  5. 5.
    Lieberthal W. Biology of acute renal failure: therapeutic implications. Kidney Int. 1997;52:1102–15.CrossRefGoogle Scholar
  6. 6.
    Sheridan AM, Bonventre JV. Cell biology and molecular mechanisms of injury in ischemic acute renal failure. Curr Opin Nephrol Hypertens. 2000;9:427–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Bush KT, Keller SH, Nigam SK. Genesis and reversal of the ischemic phenotype in epithelial cells. J Clin Invest. 2000;106:621–6. PubMed PMID: 10974012.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lieberthal W, Nigam SK, Huie P, Sibley RK, Dafoe D, Kuo P, et al. Acute renal failure. II. Experimental models of acute renal failure: imperfect but indispensable. Am J Physiol Renal Physiol. 2000;278:F1–F12. PubMed PMID: 10644651.CrossRefPubMedGoogle Scholar
  9. 9.
    Brown D, Lee R, Bonventre JV. Redistribution of villin to proximal tubule basolateral membranes after ischemia and reperfusion. Am J Physiol. 1997;273:F1003–12. PubMed PMID: 9435690.PubMedGoogle Scholar
  10. 10.
    Kellerman PS, Bogusky RT. Microfilament disruption occurs very early in ischemic proximal tubule cell injury. Kidney Int. 1992;42:896–902.CrossRefPubMedGoogle Scholar
  11. 11.
    Molitoris BA, Falk SA, Dahl RH. Ischemia-induced loss of epithelial polarity. Role of the tight junction. J Clin Invest. 1989;84:1334–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Shelden EA, Weinberg JM, Sorenson DR, Edwards CA, Pollock FM. Site-specific alteration of actin assembly visualized in living renal epithelial cells during ATP depletion. J Am Soc Nephrol. 2002;13:2667–80.CrossRefPubMedGoogle Scholar
  13. 13.
    Abbate M, Bonventre JV, Brown D. The microtubule network of renal epithelial cells is disrupted by ischemia and reperfusion. Am J Physiol. 1994;267:F971–8. PubMed PMID: 7810705.PubMedGoogle Scholar
  14. 14.
    Kwon O, Nelson WJ, Sibley R, Huie P, Scandling JD, Dafoe D, et al. Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the renal allograft. J Clin Invest. 1998;101:2054–64.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bush KT, Tsukamoto T, Nigam SK. Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial ischemia. Am J Physiol Renal Physiol. 2000;278:F847–52. PubMed PMID: 10807598.CrossRefPubMedGoogle Scholar
  16. 16.
    Fish EM, Molitoris BA. Alterations in epithelial polarity and the pathogenesis of disease states. N Engl J Med. 1994;330:1580–8. PubMed PMID: 8177249.CrossRefPubMedGoogle Scholar
  17. 17.
    Duan Y, Gotoh N, Yan Q, Du Z, Weinstein AM, Wang T, et al. Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes. Proc Natl Acad Sci U S A. 2008;105:11418–23. PubMed PMID: 18685100.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tsukamoto T, Nigam SK. Tight junction proteins form large complexes and associate with the cytoskeleton in an ATP depletion model for reversible junction assembly. J Biol Chem. 1997;272:16133–9. PubMed PMID: 9195909.CrossRefPubMedGoogle Scholar
  19. 19.
    Zuk A, Bonventre JV, Brown D, Matlin KS. Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney. Am J Physiol. 1998;275:C711–31. PubMed PMID: 9730955.CrossRefPubMedGoogle Scholar
  20. 20.
    Lieberthal W, McKenney JB, Kiefer CR, Snyder LM, Kroshian VM, Sjaastad MD. Beta1 integrin-mediated adhesion between renal tubular cells after anoxic injury. J Am Soc Nephrol. 1997;8(2):175–83. PubMed PMID: 9048335.PubMedGoogle Scholar
  21. 21.
    Molitoris BA. Actin cytoskeleton in ischemic acute renal failure. Kidney Int. 2004;66(2):871–83. PubMed PMID: 15253754.CrossRefPubMedGoogle Scholar
  22. 22.
    Donohoe JF, Venkatachalam MA, Bernard DB, Levinsky NG. Tubular leakage and obstruction after renal ischemia: structural-functional correlations. Kidney Int. 1978;13:208–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Bonventre JV, Colvin RB. Adhesion molecules in renal disease. Curr Opin Nephrol Hypertens. 1996;5(3):254–61. PubMed PMID: 8737861. Epub 1996/05/01. eng.CrossRefPubMedGoogle Scholar
  24. 24.
    Noiri E, Romanov V, Forest T, Gailit J, DiBona GF, Miller F, et al. Pathophysiology of renal tubular obstruction: therapeutic role of synthetic RGD peptides in acute renal failure. Kidney Int. 1995;48:1375–85.CrossRefPubMedGoogle Scholar
  25. 25.
    Tanner GA, Sophasan S. Kidney pressures after temporary renal artery occlusion in the rat. Am J Physiol. 1976;230(4):1173–81. PubMed PMID: 1267015.PubMedGoogle Scholar
  26. 26.
    Kwon O, Corrigan G, Myers BD, Sibley R, Scandling JD, Dafoe D, et al. Sodium reabsorption and distribution of Na+/K+-ATPase during postischemic injury to the renal allograft. Kidney Int. 1999;55:963–75.CrossRefPubMedGoogle Scholar
  27. 27.
    Molitoris BA, Dahl R, Geerdes A. Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)-K(+)-ATPase during ischemia. Am J Physiol. 1992;263:F488–95. PubMed PMID: 1329535.PubMedGoogle Scholar
  28. 28.
    Wald FA, Figueroa Y, Oriolo AS, Salas PJI. Membrane repolarization is delayed in proximal tubules after ischemia-reperfusion: possible role of microtubule-organizing centers. Am J Physiol Renal Physiol. 2003;285:F230–40. PubMed PMID: 12709392.CrossRefPubMedGoogle Scholar
  29. 29.
    Rajasekaran AK, Rajasekaran SA. Role of Na-K-ATPase in the assembly of tight junctions. Am J Physiol Renal Physiol. 2003;285:F388–96. PubMed PMID: 12890662.CrossRefPubMedGoogle Scholar
  30. 30.
    Moran SM, Myers BD. Pathophysiology of protracted acute renal failure in man. J Clin Invest. 1985;76:1440–8.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Myers BD, Chui F, Hilberman M, Michaels AS. Transtubular leakage of glomerular filtrate in human acute renal failure. Am J Physiol. 1979;237:F319–25. PubMed PMID: 495725.PubMedGoogle Scholar
  32. 32.
    Arendshorst WJ, Bello-Reuss E. The kidney. In: Bradshaw RA, Dennis EA, editors. Handbook of cell signaling. Oxford: Elsevier; 2010. p. 2707–31.CrossRefGoogle Scholar
  33. 33.
    Imig JD. Epoxyeicosatrienoic acids, hypertension, and kidney injury. Hypertension. 2015;65(3):476–82. PubMed PMID: 25583156. Pubmed Central PMCID: 4326585.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Schnermann J. Concurrent activation of multiple vasoactive signaling pathways in vasoconstriction caused by tubuloglomerular feedback: a quantitative assessment. Annu Rev Physiol. 2015;77:301–22. PubMed PMID: 25668021.CrossRefPubMedGoogle Scholar
  35. 35.
    McCullough PA, Tumlin JA. Prostaglandin-based renal protection against contrast-induced acute kidney injury. Circulation. 2009;120(18):1749–51. PubMed PMID: 19841295.CrossRefPubMedGoogle Scholar
  36. 36.
    Jia Z, Sun Y, Liu S, Liu Y, Yang T. COX-2 but not mPGES-1 contributes to renal PGE2 induction and diabetic proteinuria in mice with type-1 diabetes. PLoS One. 2014;9(7):e93182. PubMed PMID: 24984018. Pubmed Central PMCID: 4077725.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Rubattu S, Mennuni S, Testa M, Mennuni M, Pierelli G, Pagliaro B, et al. Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress? Int J Mol Sci. 2013;14(11):23011–32. PubMed PMID: 24264044. Pubmed Central PMCID: 3856103.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Rao R, Zhang MZ, Zhao M, Cai H, Harris RC, Breyer MD, et al. Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria. Am J Physiol Renal Physiol. 2005;288(4):F642–9. PubMed PMID: 15585669.CrossRefPubMedGoogle Scholar
  39. 39.
    Jia Z, Zhang Y, Ding G, Heiney KM, Huang S, Zhang A. Role of COX-2/mPGES-1/prostaglandin E2 cascade in kidney injury. Mediat Inflamm. 2015;2015:147894. PubMed PMID: 25729216. Pubmed Central PMCID: 4333324.CrossRefGoogle Scholar
  40. 40.
    Harris RC, Zhang MZ. Cyclooxygenase metabolites in the kidney. Compr Physiol. 2011;1(4):1729–58. PubMed PMID: 23733687.PubMedGoogle Scholar
  41. 41.
    Vukicevic S, Simic P, Borovecki F, Grgurevic L, Rogic D, Orlic I, et al. Role of EP2 and EP4 receptor-selective agonists of prostaglandin E(2) in acute and chronic kidney failure. Kidney Int. 2006;70(6):1099–106. PubMed PMID: 16871242.CrossRefPubMedGoogle Scholar
  42. 42.
    Spargias K, Adreanides E, Demerouti E, Gkouziouta A, Manginas A, Pavlides G, et al. Iloprost prevents contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation. 2009;120(18):1793–9. PubMed PMID: 19841299.CrossRefPubMedGoogle Scholar
  43. 43.
    Eskildsen MP, Hansen PB, Stubbe J, Toft A, Walter S, Marcussen N, et al. Prostaglandin I2 and prostaglandin E2 modulate human intrarenal artery contractility through prostaglandin E2-EP4, prostacyclin-IP, and thromboxane A2-TP receptors. Hypertension. 2014;64(3):551–6. PubMed PMID: 24914192.CrossRefPubMedGoogle Scholar
  44. 44.
    Curiel RV, Katz JD. Mitigating the cardiovascular and renal effects of NSAIDs. Pain Med. 2013;14(Suppl 1):S23–8. PubMed PMID: 24255997.CrossRefPubMedGoogle Scholar
  45. 45.
    Roman RJ, Akbulut T, Park F, Regner KR. 20-HETE in acute kidney injury. Kidney Int. 2011;79(1):10–3. PubMed PMID: 21157458. Pubmed Central PMCID: PMC3146060.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Hoff U, Lukitsch I, Chaykovska L, Ladwig M, Arnold C, Manthati VL, et al. Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury. Kidney Int. 2011;79(1):57–65. PubMed PMID: 20962739. Pubmed Central PMCID: PMC3813968.CrossRefPubMedGoogle Scholar
  47. 47.
    Park F, Sweeney WE Jr, Jia G, Akbulut T, Mueller B, Falck JR, et al. Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD. Am J Physiol Renal Physiol. 2009;296(3):F575–82. PubMed PMID: 19129252. Pubmed Central PMCID: PMC2660198.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Hong S, Lu Y. Omega-3 fatty acid-derived resolvins and protectins in inflammation resolution and leukocyte functions: targeting novel lipid mediator pathways in mitigation of acute kidney injury. Front Immunol. 2013;4:13. PubMed PMID: 23386851. Pubmed Central PMCID: 3558681.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, et al. Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol. 2006;177(9):5902–11. PubMed PMID: 17056514.CrossRefGoogle Scholar
  50. 50.
    Schwiebert EM, Zsembery A. Extracellular ATP as a signaling molecule for epithelial cells. Biochim Biophys Acta. 2003;1615(1–2):7–32. PubMed PMID: 12948585.CrossRefPubMedGoogle Scholar
  51. 51.
    Solini A, Usuelli V, Fiorina P. The dark side of extracellular ATP in kidney diseases. J Am Soc Nephrol. 2015;26(5):1007–16. PubMed PMID: 25452669. Pubmed Central PMCID: 4413770.CrossRefGoogle Scholar
  52. 52.
    Howarth AR, Conway BR, Bailey MA. Vascular and inflammatory actions of P2X receptors in renal injury. Auton Neurosci. 2015;191:135–40. PubMed PMID: 25998687.CrossRefGoogle Scholar
  53. 53.
    Rosin DL, Okusa MD. Dangers within: DAMP responses to damage and cell death in kidney disease. J Am Soc Nephrol. 2011;22(3):416–25. PubMed PMID: 21335516. Pubmed Central PMCID: PMC4493973.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Menzies RI, Howarth AR, Unwin RJ, Tam FW, Mullins JJ, Bailey MA. Inhibition of the purinergic P2X7 receptor improves renal perfusion in angiotensin-II-infused rats. Kidney Int. 2015;88(5):1079–87. PubMed PMID: 26108066.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Yan Y, Bai J, Zhou X, Tang J, Jiang C, Tolbert E, et al. P2X7 receptor inhibition protects against ischemic acute kidney injury in mice. Am J Physiol Cell Physiol. 2015;308(6):C463–72. PubMed PMID: 25588875. Pubmed Central PMCID: 4360025.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Baylis C. Nitric oxide synthase derangements and hypertension in kidney disease. Curr Opin Nephrol Hypertens. 2012;21(1):1–6. PubMed PMID: 22048724. Pubmed Central PMCID: 3277934.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Horita S, Nakamura M, Shirai A, Yamazaki O, Satoh N, Suzuki M, et al. Regulatory roles of nitric oxide and angiotensin II on renal tubular transport. World J Nephrol. 2014;3(4):295–301. PubMed PMID: 25374825. Pubmed Central PMCID: 4220364.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Baylis C. Nitric oxide deficiency in chronic kidney disease. Am J Physiol Renal Physiol. 2008;294(1):F1–9. PubMed PMID: 17928410.CrossRefPubMedGoogle Scholar
  59. 59.
    Koul V, Kaur A, Singh AP. Investigation of the role of nitric oxide/soluble guanylyl cyclase pathway in ascorbic acid-mediated protection against acute kidney injury in rats. Mol Cell Biochem. 2015;406(1–2):1–7. PubMed PMID: 26142728.CrossRefPubMedGoogle Scholar
  60. 60.
    Amaral JH, Ferreira GC, Pinheiro LC, Montenegro MF, Tanus-Santos JE. Consistent antioxidant and antihypertensive effects of oral sodium nitrite in DOCA-salt hypertension. Redox Biol. 2015;5:340–6. PubMed PMID: 26119848. Pubmed Central PMCID: 4491646.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Choi MR, Kouyoumdzian NM, Rukavina Mikusic NL, Kravetz MC, Roson MI, Rodriguez Fermepin M, et al. Renal dopaminergic system: pathophysiological implications and clinical perspectives. World J Nephrol. 2015;4(2):196–212. PubMed PMID: 25949933. Pubmed Central PMCID: 4419129.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Carey RM. The intrarenal renin-angiotensin and dopaminergic systems: control of renal sodium excretion and blood pressure. Hypertension. 2013;61(3):673–80. PubMed PMID: 23407646. Pubmed Central PMCID: 3577093.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Patel NN, Rogers CA, Angelini GD, Murphy GJ. Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review. Heart Fail Rev. 2011;16(6):553–67. PubMed PMID: 21400231.CrossRefPubMedGoogle Scholar
  64. 64.
    Carey RM. The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 2015;22(3):204–10. PubMed PMID: 25908469.CrossRefPubMedGoogle Scholar
  65. 65.
    Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006;103(47):17985–90. PubMed PMID: 17090678. Pubmed Central PMCID: 1693859.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Macconi D, Remuzzi G, Benigni A. Key fibrogenic mediators: old players. Renin-angiotensin system. Kidney Int Suppl. 2014;4(1):58–64. PubMed PMID: 26312151. Pubmed Central PMCID: 4536968.CrossRefGoogle Scholar
  67. 67.
    Schrimpf C, Teebken OE, Wilhelmi M, Duffield JS. The role of pericyte detachment in vascular rarefaction. J Vasc Res. 2014;51(4):247–58. PubMed PMID: 25195856. Pubmed Central PMCID: 4476411.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Huang Q, Wang Q, Zhang S, Jiang S, Zhao L, Yu L, et al. Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischemia-reperfusion injury. Acta Physiol. 2016;218(2):136–45. PubMed PMID: 27362287.CrossRefGoogle Scholar
  69. 69.
    Campbell DJ, Kladis A, Duncan AM. Bradykinin peptides in kidney, blood, and other tissues of the rat. Hypertension. 1993;21(2):155–65. PubMed PMID: 8428778.CrossRefPubMedGoogle Scholar
  70. 70.
    Mamenko M, Zaika O, Pochynyuk O. Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling. Curr Opin Nephrol Hypertens. 2014;23(2):122–9. PubMed PMID: 24378775. Pubmed Central PMCID: 4114036.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Bulut OP, Dipp S, El-Dahr S. Ontogeny of bradykinin B1 receptors in the mouse kidney. Pediatr Res. 2009;66(5):519–23. PubMed PMID: 19581823. Pubmed Central PMCID: 2783398.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Kayashima Y, Smithies O, Kakoki M. The kallikrein-kinin system and oxidative stress. Curr Opin Nephrol Hypertens. 2012;21(1):92–6. PubMed PMID: 22048723. Pubmed Central PMCID: 3657726.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Estrela GR, Wasinski F, Almeida DC, Amano MT, Castoldi A, Dias CC, et al. Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration. J Mol Med. 2014;92(4):399–409. PubMed PMID: 24357263.CrossRefPubMedGoogle Scholar
  74. 74.
    Estrela GR, Wasinski F, Bacurau RF, Malheiros DM, Camara NO, Araujo RC. Kinin B2 receptor deletion and blockage ameliorates cisplatin-induced acute renal injury. Int Immunopharmacol. 2014;22(1):115–9. PubMed PMID: 24975837.CrossRefPubMedGoogle Scholar
  75. 75.
    Huart A, Klein J, Gonzalez J, Buffin-Meyer B, Neau E, Delage C, et al. Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. Front Pharmacol. 2015;6:8. PubMed PMID: 25698969. Pubmed Central PMCID: 4313587.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ, et al. Different faces of the heme-heme oxygenase system in inflammation. Pharmacol Rev. 2003;55(3):551–71. PubMed PMID: 12869663.CrossRefPubMedGoogle Scholar
  77. 77.
    Akagi R, Takahashi T, Sassa S. Cytoprotective effects of heme oxygenase in acute renal failure. Contrib Nephrol. 2005;148:70–85. PubMed PMID: 15912028.CrossRefPubMedGoogle Scholar
  78. 78.
    Lai IR, Ma MC, Chen CF, Chang KJ. The protective role of heme oxygenase-1 on the liver after hypoxic preconditioning in rats. Transplantation. 2004;77(7):1004–8. PubMed PMID: 15087761.CrossRefPubMedGoogle Scholar
  79. 79.
    Vera T, Henegar JR, Drummond HA, Rimoldi JM, Stec DE. Protective effect of carbon monoxide-releasing compounds in ischemia-induced acute renal failure. J Am Soc Nephrol. 2005;16(4):950–8. PubMed PMID: 15728782.CrossRefPubMedGoogle Scholar
  80. 80.
    Morimoto K, Ohta K, Yachie A, Yang Y, Shimizu M, Goto C, et al. Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases. Kidney Int. 2001;60(5):1858–66. PubMed PMID: 11703604.CrossRefPubMedGoogle Scholar
  81. 81.
    Koizumi S. Human heme oxygenase-1 deficiency: a lesson on serendipity in the discovery of the novel disease. Pediatr Int. 2007;49(2):125–32. PubMed PMID: 17445026.CrossRefPubMedGoogle Scholar
  82. 82.
    Pittock ST, Norby SM, Grande JP, Croatt AJ, Bren GD, Badley AD, et al. MCP-1 is up-regulated in unstressed and stressed HO-1 knockout mice: pathophysiologic correlates. Kidney Int. 2005;68(2):611–22. PubMed PMID: 16014038.CrossRefPubMedGoogle Scholar
  83. 83.
    Shiraishi F, Curtis LM, Truong L, Poss K, Visner GA, Madsen K, et al. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am J Physiol Renal Physiol. 2000;278(5):F726–36. PubMed PMID: 10807584. Epub 2000/05/12. eng.CrossRefPubMedGoogle Scholar
  84. 84.
    Nath KA, Haggard JJ, Croatt AJ, Grande JP, Poss KD, Alam J. The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. Am J Pathol. 2000;156(5):1527–35. PubMed PMID: 10793064.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Maines MD, Mayer RD, Ewing JF, McCoubrey WK Jr. Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. J Pharmacol Exp Ther. 1993;264(1):457–62. PubMed PMID: 8423544.PubMedGoogle Scholar
  86. 86.
    Ollinger R, Kogler P, Biebl M, Sieb M, Sucher R, Bosmuller C, et al. Protein levels of heme oxygenase-1 during reperfusion in human kidney transplants with delayed graft function. Clin Transpl. 2008;22(4):418–23. PubMed PMID: 18261117.CrossRefGoogle Scholar
  87. 87.
    Billings FT 4th, Yu C, Byrne JG, Petracek MR, Pretorius M. Heme oxygenase-1 and acute kidney injury following cardiac surgery. Cardiorenal Med. 2014;4(1):12–21. PubMed PMID: 24847330. Pubmed Central PMCID: PMC4024967.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Nath KA. Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int. 2006;70(3):432–43. PubMed PMID: 16775600.CrossRefPubMedGoogle Scholar
  89. 89.
    Appleton SD, Chretien ML, McLaughlin BE, Vreman HJ, Stevenson DK, Brien JF, et al. Selective inhibition of heme oxygenase, without inhibition of nitric oxide synthase or soluble guanylyl cyclase, by metalloporphyrins at low concentrations. Drug Metab Dispos. 1999;27(10):1214–9. PubMed PMID: 10497150.PubMedGoogle Scholar
  90. 90.
    Zou AP, Billington H, Su N, Cowley AW Jr. Expression and actions of heme oxygenase in the renal medulla of rats. Hypertension. 2000;35(1 Pt 2):342–7. PubMed PMID: 10642322.CrossRefPubMedGoogle Scholar
  91. 91.
    Holzen JP, August C, Bahde R, Minin E, Lang D, Heidenreich S, et al. Influence of heme oxygenase-1 on microcirculation after kidney transplantation. J Surg Res. 2008;148(2):126–35. PubMed PMID: 18456280.CrossRefPubMedGoogle Scholar
  92. 92.
    Chlopicki S, Olszanecki R, Marcinkiewicz E, Lomnicka M, Motterlini R. Carbon monoxide released by CORM-3 inhibits human platelets by a mechanism independent of soluble guanylate cyclase. Cardiovasc Res. 2006;71(2):393–401. PubMed PMID: 16713591.CrossRefPubMedGoogle Scholar
  93. 93.
    Ren Y, D’Ambrosio MA, Wang H, Liu R, Garvin JL, Carretero OA. Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF). Am J Physiol Renal Physiol. 2008;295(4):F1207–12. PubMed PMID: 18715939. Pubmed Central PMCID: 2576153. Epub 2008/08/22. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Nakao A, Neto JS, Kanno S, Stolz DB, Kimizuka K, Liu F, et al. Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both. Am J Transplant. 2005;5(2):282–91. PubMed PMID: 15643987.CrossRefPubMedGoogle Scholar
  95. 95.
    Bolisetty S, Traylor AM, Kim J, Joseph R, Ricart K, Landar A, et al. Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury. J Am Soc Nephrol. 2010;21(10):1702–12. PubMed PMID: 20705711. Pubmed Central PMCID: PMC3013546.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Bolisetty S, Traylor A, Zarjou A, Johnson MS, Benavides GA, Ricart K, et al. Mitochondria-targeted heme oxygenase-1 decreases oxidative stress in renal epithelial cells. Am J Physiol Renal Physiol. 2013;305(3):F255–64. PubMed PMID: 23720344. Pubmed Central PMCID: PMC3742869.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Inguaggiato P, Gonzalez-Michaca L, Croatt AJ, Haggard JJ, Alam J, Nath KA. Cellular overexpression of heme oxygenase-1 up-regulates p21 and confers resistance to apoptosis. Kidney Int. 2001;60(6):2181–91. PubMed PMID: 11737592. Epub 2001/12/12. eng.CrossRefPubMedGoogle Scholar
  98. 98.
    Andersen MH. Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients. J Clin Invest. 2009;119(8):2245–56.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Ferenbach DA, Nkejabega NC, McKay J, Choudhary AK, Vernon MA, Beesley MF, et al. The induction of macrophage hemeoxygenase-1 is protective during acute kidney injury in aging mice. Kidney Int. 2011;79(9):966–76. PubMed PMID: 21248714. Epub 2011/01/21. Eng.CrossRefPubMedGoogle Scholar
  100. 100.
    Hull TD, Kamal AI, Boddu R, Bolisetty S, Guo L, Tisher CC, et al. Heme oxygenase-1 regulates myeloid cell trafficking in AKI. J Am Soc Nephrol. 2015;26(9):2139–51. PubMed PMID: 25677389. Pubmed Central PMCID: PMC4552119.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Kim J, Zarjou A, Traylor AM, Bolisetty S, Jaimes EA, Hull TD, et al. In vivo regulation of the heme oxygenase-1 gene in humanized transgenic mice. Kidney Int. 2012;82(3):278–91. PubMed PMID: 22495295. Pubmed Central PMCID: PMC3396739.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Ali F, Zakkar M, Karu K, Lidington EA, Hamdulay SS, Boyle JJ, et al. Induction of the cytoprotective enzyme heme oxygenase-1 by statins is enhanced in vascular endothelium exposed to laminar shear stress and impaired by disturbed flow. J Biol Chem. 2009;284(28):18882–92. PubMed PMID: 19457866. Pubmed Central PMCID: PMC2707208.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Billings FT 4th, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, et al. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA. 2016;315(9):877–88. PubMed PMID: 26906014. Pubmed Central PMCID: PMC4843765.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Wu BJ, Kathir K, Witting PK, Beck K, Choy K, Li C, et al. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging. J Exp Med. 2006;203(4):1117–27. PubMed PMID: 16606673.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Kubulus D, Rensing H, Paxian M, Thierbach JT, Meisel T, Redl H, et al. Influence of heme-based solutions on stress protein expression and organ failure after hemorrhagic shock. Crit Care Med. 2005;33(3):629–37. PubMed PMID: 15753757.CrossRefPubMedGoogle Scholar
  106. 106.
    Tenhunen R, Tokola O, Linden IB. Haem arginate: a new stable haem compound. J Pharm Pharmacol. 1987;39(10):780–6. PubMed PMID: 2891815.CrossRefPubMedGoogle Scholar
  107. 107.
    Ventura P, Cappellini MD, Rocchi E. The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine. Intern Emerg Med. 2009;4(4):297–308. PubMed PMID: 19479318.CrossRefPubMedGoogle Scholar
  108. 108.
    Thomas RA, Czopek A, Bellamy CO, McNally SJ, Kluth DC, Marson LP. Hemin preconditioning upregulates heme oxygenase-1 in deceased donor renal transplant recipients: a randomized, controlled, phase IIB trial. Transplantation. 2016;100(1):176–83. PubMed PMID: 26680374.CrossRefPubMedGoogle Scholar
  109. 109.
    Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121(11):4210–21. PubMed PMID: 22045571. Pubmed Central PMCID: 3204829.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Mulay SR, Holderied A, Kumar SV, Anders HJ. Targeting inflammation in so-called acute kidney injury. Semin Nephrol. 2016;36(1):17–30. PubMed PMID: 27085732.CrossRefPubMedGoogle Scholar
  111. 111.
    He Z, Lu L, Altmann C, Hoke TS, Ljubanovic D, Jani A, et al. Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury. Am J Physiol Renal Physiol. 2008;295(5):F1414–21. PubMed PMID: 18753296. Pubmed Central PMCID: 2584896. Epub 2008/08/30. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, et al. Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther. 2007;322(1):8–15. PubMed PMID: 17400889.CrossRefPubMedGoogle Scholar
  113. 113.
    Wang W, Faubel S, Ljubanovic D, Mitra A, Falk SA, Kim J, et al. Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice. Am J Physiol Renal Physiol. 2005;288(5):F997–1004. PubMed PMID: 15644489.CrossRefPubMedGoogle Scholar
  114. 114.
    Linkermann A, Brasen JH, Darding M, Jin MK, Sanz AB, Heller JO, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2013;110(29):12024–9. PubMed PMID: 23818611. Pubmed Central PMCID: PMC3718149.CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Linkermann A, Green DR. Necroptosis. N Engl J Med. 2014;370(5):455–65. PubMed PMID: 24476434. Pubmed Central PMCID: PMC4035222.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Linkermann A, Hackl MJ, Kunzendorf U, Walczak H, Krautwald S, Jevnikar AM. Necroptosis in immunity and ischemia-reperfusion injury. Am J Transplant. 2013;13(11):2797–804. PubMed PMID: 24103029.CrossRefPubMedGoogle Scholar
  117. 117.
    Ferenbach DA, Kluth DC, Hughes J. Hemeoxygenase-1 and renal ischaemia-reperfusion injury. Nephron Exp Nephrol. 2010;115(3):e33–7. PubMed PMID: 20424481. Epub 2010/04/29. eng.CrossRefPubMedGoogle Scholar
  118. 118.
    Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;16(12):1180–91. PubMed PMID: 25402683. Pubmed Central PMCID: PMC4894846.CrossRefPubMedGoogle Scholar
  119. 119.
    Kumar SV, Kulkarni OP, Mulay SR, Darisipudi MN, Romoli S, Thomasova D, et al. Neutrophil extracellular trap-related extracellular histones cause vascular necrosis in severe GN. J Am Soc Nephrol. 2015;26(10):2399–413. PubMed PMID: 25644111. Pubmed Central PMCID: PMC4587690.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Yang H, Fogo AB. Cell senescence in the aging kidney. J Am Soc Nephrol. 2010;21(9):1436–9. PubMed PMID: 20705707. Epub 2010/08/14. eng.CrossRefPubMedGoogle Scholar
  121. 121.
    Baker DJ, Wijshake T, Tchkonia T, Lebrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16(Ink4a)-positive senescent cells delays ageing-associated disorders. Nature. 2011;479(7372):232–6. PubMed PMID: 22048312. Epub 2011/11/04. Eng.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016;530(7589):184–9. PubMed PMID: 26840489. Pubmed Central PMCID: 4845101.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Grgic I, Campanholle G, Bijol V, Wang C, Sabbisetti VS, Ichimura T, et al. Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis. Kidney Int. 2012;82(2):172–83. PubMed PMID: 22437410. Epub 2012/03/23. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Venkatachalam MA, Weinberg JM, Kriz W, Bidani AK. Failed tubule recovery, AKI-CKD transition, and kidney disease progression. J Am Soc Nephrol. 2015;26(8):1765–76. PubMed PMID: 25810494. Pubmed Central PMCID: 4520181.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Lan R, Geng H, Polichnowski AJ, Singha PK, Saikumar P, McEwen DG, et al. PTEN loss defines a TGF-beta-induced tubule phenotype of failed differentiation and JNK signaling during renal fibrosis. Am J Physiol Renal Physiol. 2012;302(9):F1210–23. PubMed PMID: 22301622. Pubmed Central PMCID: 3362177. Epub 2012/02/04. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    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):535–43, 1p following 143. PubMed PMID: 20436483. Epub 2010/05/04. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Tang J, Liu N, Tolbert E, Ponnusamy M, Ma L, Gong R, et al. Sustained activation of EGFR triggers renal fibrogenesis after acute kidney injury. Am J Pathol. 2013;183(1):160–72. PubMed PMID: 23684791. Pubmed Central PMCID: 3702747.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Cianciolo Cosentino C, Skrypnyk NI, Brilli LL, Chiba T, Novitskaya T, Woods C, et al. Histone deacetylase inhibitor enhances recovery after AKI. J Am Soc Nephrol. 2013;24(6):943–53. PubMed PMID: 23620402. Pubmed Central PMCID: 3665399. Epub 2013/04/27. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Wu CF, Chiang WC, Lai CF, Chang FC, Chen YT, Chou YH, et al. Transforming growth factor beta-1 stimulates profibrotic epithelial signaling to activate pericyte-myofibroblast transition in obstructive kidney fibrosis. Am J Pathol. 2013;182(1):118–31. PubMed PMID: 23142380. Pubmed Central PMCID: 3538028.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 2004;66(2):480–5. PubMed PMID: 15253693.CrossRefPubMedGoogle Scholar
  131. 131.
    Furuichi K, Gao JL, Horuk R, Wada T, Kaneko S, Murphy PM. Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury. J Immunol. 2008;181(12):8670–6. PubMed PMID: 19050287. Pubmed Central PMCID: PMC2633769.CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Furuichi K, Gao JL, Murphy PM. Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury. Am J Pathol. 2006;169(2):372–87. PubMed PMID: 16877340.CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Furuichi K, Wada T, Iwata Y, Kitagawa K, Kobayashi K, Hashimoto H, et al. CCR2 signaling contributes to ischemia-reperfusion injury in kidney. J Am Soc Nephrol. 2003;14(10):2503–15. PubMed PMID: 14514728.CrossRefPubMedGoogle Scholar
  134. 134.
    Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD. Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. Kidney Int. 2007;71(7):619–28. PubMed PMID: 17311071. Epub 2007/02/22. eng.CrossRefPubMedGoogle Scholar
  135. 135.
    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):859–64. PubMed PMID: 19562316.CrossRefPubMedGoogle Scholar
  136. 136.
    Daemen MA, de Vries B, van’t Veer C, Wolfs TG, Buurman WA. Apoptosis and chemokine induction after renal ischemia-reperfusion. Transplantation. 2001;71(7):1007–11. PubMed PMID: 11349710.CrossRefPubMedGoogle Scholar
  137. 137.
    Ysebaert DK, De Greef KE, Vercauteren SR, Ghielli M, Verpooten GA, Eyskens EJ, et al. Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant. 2000;15(10):1562–74. PubMed PMID: 11007823.CrossRefPubMedGoogle Scholar
  138. 138.
    Miura M, Fu X, Zhang QW, Remick DG, Fairchild RL. Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury. Am J Pathol. 2001;159(6):2137–45. PubMed PMID: 11733364. Pubmed Central PMCID: PMC1850606.CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Kelly KJ, Williams WW Jr, Colvin RB, Bonventre JV. Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury. Proc Natl Acad Sci U S A. 1994;91(2):812–6. PubMed PMID: 7904759.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Paller MS. Effect of neutrophil depletion on ischemic renal injury in the rat. J Lab Clin Med. 1989;113(3):379–86. PubMed PMID: 2926243.PubMedGoogle Scholar
  141. 141.
    Thornton MA, Winn R, Alpers CE, Zager RA. An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury. Am J Pathol. 1989;135(3):509–15. PubMed PMID: 2782382. Pubmed Central PMCID: 1879883.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Tadagavadi RK, Gao G, Wang WW, Gonzalez MR, Reeves WB. Dendritic cell protection from cisplatin nephrotoxicity is independent of neutrophils. Toxins. 2015;7(8):3245–56. PubMed PMID: 26295408. Pubmed Central PMCID: PMC4549748.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Jang HR, Park JH, Kwon GY, Park JB, Lee JE, Kim DJ, et al. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice. Am J Physiol Renal Physiol. 2016;310(4):F272–83. PubMed PMID: 26661651.CrossRefPubMedGoogle Scholar
  144. 144.
    Salmela K, Wramner L, Ekberg H, Hauser I, Bentdal O, Lins LE, et al. A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group. Transplantation. 1999;67(5):729–36. PubMed PMID: 10096530.CrossRefPubMedGoogle Scholar
  145. 145.
    Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int. 2004;66(2):486–91. PubMed PMID: 15253694.CrossRefPubMedGoogle Scholar
  146. 146.
    Burne MJ, Daniels F, El Ghandour A, Mauiyyedi S, Colvin RB, O’Donnell MP, et al. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure. J Clin Invest. 2001;108(9):1283–90. PubMed PMID: 11696572.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Burne-Taney MJ, Yokota-Ikeda N, Rabb H. Effects of combined T- and B-cell deficiency on murine ischemia reperfusion injury. Am J Transplant. 2005;5(6):1186–93. PubMed PMID: 15888022.CrossRefPubMedGoogle Scholar
  148. 148.
    Yokota N, Daniels F, Crosson J, Rabb H. Protective effect of T cell depletion in murine renal ischemia-reperfusion injury. Transplantation. 2002;74(6):759–63. PubMed PMID: 12364852.CrossRefPubMedGoogle Scholar
  149. 149.
    Rabb H, Daniels F, O’Donnell M, Haq M, Saba SR, Keane W, et al. Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice. Am J Physiol Renal Physiol. 2000;279(3):F525–31. PubMed PMID: 10966932.CrossRefPubMedGoogle Scholar
  150. 150.
    Rabb H. The T cell as a bridge between innate and adaptive immune systems: implications for the kidney. Kidney Int. 2002;61(6):1935–46. PubMed PMID: 12028434.CrossRefPubMedGoogle Scholar
  151. 151.
    Burne-Taney MJ, Ascon DB, Daniels F, Racusen L, Baldwin W, Rabb H. B cell deficiency confers protection from renal ischemia reperfusion injury. J Immunol. 2003;171(6):3210–5. PubMed PMID: 12960350.CrossRefPubMedGoogle Scholar
  152. 152.
    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):F352–7. PubMed PMID: 11788450.CrossRefPubMedGoogle Scholar
  153. 153.
    Gandolfo MT, Jang HR, Bagnasco SM, Ko GJ, Agreda P, Satpute SR, et al. Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury. Kidney Int. 2009;76(7):717–29. PubMed PMID: 19625990.CrossRefPubMedGoogle Scholar
  154. 154.
    Erwig LP, Kluth DC, Rees AJ. Macrophages in renal inflammation. Curr Opin Nephrol Hypertens. 2001;10(3):341–7. PubMed PMID: 11342795.CrossRefPubMedGoogle Scholar
  155. 155.
    Jose MD, Ikezumi Y, van Rooijen N, Atkins RC, Chadban SJ. Macrophages act as effectors of tissue damage in acute renal allograft rejection. Transplantation. 2003;76(7):1015–22. PubMed PMID: 14557746.CrossRefPubMedGoogle Scholar
  156. 156.
    Kluth DC, Erwig LP, Rees AJ. Multiple facets of macrophages in renal injury. Kidney Int. 2004;66(2):542–57. PubMed PMID: 15253705.CrossRefPubMedGoogle Scholar
  157. 157.
    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):F722–31. PubMed PMID: 15561971.CrossRefPubMedGoogle Scholar
  158. 158.
    Jo SK, Sung SA, Cho WY, Go KJ, Kim HK. Macrophages contribute to the initiation of ischaemic acute renal failure in rats. Nephrol Dial Transplant. 2006;21(5):1231–9. PubMed PMID: 16410269. Epub 2006/01/18. eng.CrossRefPubMedGoogle Scholar
  159. 159.
    Duffield JS, Tipping PG, Kipari T, Cailhier JF, Clay S, Lang R, et al. Conditional ablation of macrophages halts progression of crescentic glomerulonephritis. Am J Pathol. 2005;167(5):1207–19. PubMed PMID: 16251406.CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, et al. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol. 2008;172(2):288–98. PubMed PMID: 18202187.CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    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):842–52. PubMed PMID: 17984109. Epub 2007/11/07. eng.CrossRefPubMedGoogle Scholar
  162. 162.
    Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22(2):317–26. PubMed PMID: 21289217. Epub 2011/02/04. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Ricardo SD, van Goor H, Eddy AA. Macrophage diversity in renal injury and repair. J Clin Invest. 2008;118(11):3522–30. PubMed PMID: 18982158.CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Rogers NM, Ferenbach DA, Isenberg JS, Thomson AW, Hughes J. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat Rev Nephrol. 2014;10(11):625–43. PubMed PMID: 25266210.CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Duffield JS, Erwig LP, Wei X, Liew FY, Rees AJ, Savill JS. Activated macrophages direct apoptosis and suppress mitosis of mesangial cells. J Immunol. 2000;164(4):2110–9. PubMed PMID: 10657665.CrossRefPubMedGoogle Scholar
  166. 166.
    Ikezumi Y, Atkins RC, Nikolic-Paterson DJ. Interferon-gamma augments acute macrophage-mediated renal injury via a glucocorticoid-sensitive mechanism. J Am Soc Nephrol. 2003;14(4):888–98. PubMed PMID: 12660323.CrossRefPubMedGoogle Scholar
  167. 167.
    Kipari T, Cailhier JF, Ferenbach D, Watson S, Houlberg K, Walbaum D, et al. Nitric oxide is an important mediator of renal tubular epithelial cell death in vitro and in murine experimental hydronephrosis. Am J Pathol. 2006;169(2):388–99. PubMed PMID: 16877341.CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    Qi F, Adair A, Ferenbach D, Vass DG, Mylonas KJ, Kipari T, et al. Depletion of cells of monocyte lineage prevents loss of renal microvasculature in murine kidney transplantation. Transplantation. 2008;86(9):1267–74. PubMed PMID: 19005409. Epub 2008/11/14. eng.CrossRefPubMedGoogle Scholar
  169. 169.
    Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schroeder A, Neuhofer W, et al. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. J Clin Invest. 2015;125(11):4223–38. PubMed PMID: 26485286. Pubmed Central PMCID: 4639967.CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Kim MG, Kim SC, Ko YS, Lee HY, Jo SK, Cho W. The role of M2 macrophages in the progression of chronic kidney disease following acute kidney injury. PLoS One. 2015;10(12):e0143961. PubMed PMID: 26630505. Pubmed Central PMCID: 4667939.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958–69. PubMed PMID: 19029990. Pubmed Central PMCID: 2724991. Epub 2008/11/26. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Lewis C, Murdoch C. Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies. Am J Pathol. 2005;167(3):627–35. PubMed PMID: 16127144.CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Murdoch C, Muthana M, Lewis CE. Hypoxia regulates macrophage functions in inflammation. J Immunol. 2005;175(10):6257–63. PubMed PMID: 16272275.CrossRefPubMedGoogle Scholar
  174. 174.
    Anders HJ, Frink M, Linde Y, Banas B, Wornle M, Cohen CD, et al. CC chemokine ligand 5/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration. J Immunol. 2003;170(11):5658–66. PubMed PMID: 12759447.CrossRefPubMedGoogle Scholar
  175. 175.
    Ling H, Edelstein C, Gengaro P, Meng X, Lucia S, Knotek M, et al. Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am J Physiol. 1999;277(3 Pt 2):F383–90. PubMed PMID: 10484522.PubMedGoogle Scholar
  176. 176.
    Noiri E, Peresleni T, Miller F, Goligorsky MS. In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest. 1996;97(10):2377–83. PubMed PMID: 8636419.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Walker LM, Walker PD, Imam SZ, Ali SF, Mayeux PR. Evidence for peroxynitrite formation in renal ischemia-reperfusion injury: studies with the inducible nitric oxide synthase inhibitor L-N(6)-(1-Iminoethyl)lysine. J Pharmacol Exp Ther. 2000;295(1):417–22. PubMed PMID: 10992009.PubMedGoogle Scholar
  178. 178.
    Tarzi RM, Davies KA, Claassens JW, Verbeek JS, Walport MJ, Cook HT. Both Fcgamma receptor I and Fcgamma receptor III mediate disease in accelerated nephrotoxic nephritis. Am J Pathol. 2003;162(5):1677–83. PubMed PMID: 12707052.CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Tarzi RM, Davies KA, Robson MG, Fossati-Jimack L, Saito T, Walport MJ, et al. Nephrotoxic nephritis is mediated by Fcgamma receptors on circulating leukocytes and not intrinsic renal cells. Kidney Int. 2002;62(6):2087–96. PubMed PMID: 12427132.CrossRefPubMedGoogle Scholar
  180. 180.
    Komine-Kobayashi M, Chou N, Mochizuki H, Nakao A, Mizuno Y, Urabe T. Dual role of Fcgamma receptor in transient focal cerebral ischemia in mice. Stroke. 2004;35(4):958–63. PubMed PMID: 14988576.CrossRefPubMedGoogle Scholar
  181. 181.
    Ferenbach D, Hughes J. Macrophages and dendritic cells: what is the difference? Kidney Int. 2008;74(1):5–7. PubMed PMID: 18560360.CrossRefPubMedGoogle Scholar
  182. 182.
    Martinez-Pomares L, Gordon S. Antigen presentation the macrophage way. Cell. 2007;131(4):641–3. PubMed PMID: 18022354.CrossRefPubMedGoogle Scholar
  183. 183.
    Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity. 2003;19(1):59–70. PubMed PMID: 12871639.CrossRefGoogle Scholar
  184. 184.
    Stary G, Bangert C, Tauber M, Strohal R, Kopp T, Stingl G. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med. 2007;204(6):1441–51. PubMed PMID: 17535975.CrossRefPubMedPubMedCentralGoogle Scholar
  185. 185.
    Auffray C, Fogg DK, Narni-Mancinelli E, Senechal B, Trouillet C, Saederup N, et al. CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation. J Exp Med. 2009;206(3):595–606. PubMed PMID: 19273628. Pubmed Central PMCID: 2699130. Epub 2009/03/11. eng.CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol. 2008;181(9):5829–35. PubMed PMID: 18941170. Epub 2008/10/23. eng.CrossRefGoogle Scholar
  187. 187.
    Anderson KV, Jurgens G, Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell. 1985;42(3):779–89. PubMed PMID: 3931918.CrossRefPubMedGoogle Scholar
  188. 188.
    Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7. PubMed PMID: 9237759.CrossRefPubMedGoogle Scholar
  189. 189.
    Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998;282(5396):2085–8. PubMed PMID: 9851930.CrossRefGoogle Scholar
  190. 190.
    Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K, Nagai Y, et al. Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol. 2002;169(4):2026–33. PubMed PMID: 12165529.CrossRefPubMedGoogle Scholar
  191. 191.
    Kim BS, Lim SW, Li C, Kim JS, Sun BK, Ahn KO, et al. Ischemia-reperfusion injury activates innate immunity in rat kidneys. Transplantation. 2005;79(10):1370–7. PubMed PMID: 15912106.CrossRefPubMedGoogle Scholar
  192. 192.
    Wolfs TG, Buurman WA, van Schadewijk A, de Vries B, Daemen MA, Hiemstra PS, et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol. 2002;168(3):1286–93. PubMed PMID: 11801667.CrossRefPubMedGoogle Scholar
  193. 193.
    Leemans JC, Stokman G, Claessen N, Rouschop KM, Teske GJ, Kirschning CJ, et al. Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J Clin Invest. 2005;115(10):2894–903. PubMed PMID: 16167081. Pubmed Central PMCID: PMC1201659.CrossRefPubMedPubMedCentralGoogle Scholar
  194. 194.
    Pulskens WP, Teske GJ, Butter LM, Roelofs JJ, van der Poll T, Florquin S, et al. Toll-like receptor-4 coordinates the innate immune response of the kidney to renal ischemia/reperfusion injury. PLoS One. 2008;3(10):e3596. PubMed PMID: 18974879. Pubmed Central PMCID: PMC2570789.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Palermo M, Alves-Rosa F, Rubel C, Fernandez GC, Fernandez-Alonso G, Alberto F, et al. Pretreatment of mice with lipopolysaccharide (LPS) or IL-1beta exerts dose-dependent opposite effects on Shiga toxin-2 lethality. Clin Exp Immunol. 2000;119(1):77–83. PubMed PMID: 10606967. Pubmed Central PMCID: PMC1905548.CrossRefPubMedPubMedCentralGoogle Scholar
  196. 196.
    Valles PG, Melechuck S, Gonzalez A, Manucha W, Bocanegra V, Valles R. Toll-like receptor 4 expression on circulating leucocytes in hemolytic uremic syndrome. Pediatr Nephrol. 2012;27(3):407–15. PubMed PMID: 21969092.CrossRefPubMedGoogle Scholar
  197. 197.
    Goligorsky MS. TLR4 and HMGB1: partners in crime? Kidney Int. 2011;80(5):450–2. PubMed PMID: 21841835.CrossRefPubMedGoogle Scholar
  198. 198.
    Chen J, Hartono JR, John R, Bennett M, Zhou XJ, Wang Y, et al. Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4. Kidney Int. 2011;80(5):504–15. PubMed PMID: 21633411. Pubmed Central PMCID: PMC3394593.CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    Li J, Gong Q, Zhong S, Wang L, Guo H, Xiang Y, et al. Neutralization of the extracellular HMGB1 released by ischaemic damaged renal cells protects against renal ischaemia-reperfusion injury. Nephrol Dial Transplant. 2011;26(2):469–78. PubMed PMID: 20679140.CrossRefPubMedGoogle Scholar
  200. 200.
    Kulkarni OP, Hartter I, Mulay SR, Hagemann J, Darisipudi MN, Kumar Vr S, et al. Toll-like receptor 4-induced IL-22 accelerates kidney regeneration. J Am Soc Nephrol. 2014;25(5):978–89. PubMed PMID: 24459235. Pubmed Central PMCID: PMC4005301.CrossRefPubMedPubMedCentralGoogle Scholar
  201. 201.
    Anders HJ. Four danger response programs determine glomerular and tubulointerstitial kidney pathology: clotting, inflammation, epithelial and mesenchymal healing. Organogenesis. 2012;8(2):29–40. PubMed PMID: 22692229. Pubmed Central PMCID: PMC3429510.CrossRefPubMedPubMedCentralGoogle Scholar
  202. 202.
    Strainic MG, Shevach EM, An F, Lin F, Medof ME. Absence of signaling into CD4+ cells via C3aR and C5aR enables autoinductive TGF-β[beta]1 signaling and induction of Foxp3+ regulatory T cells. Nat Immunol. 2012;14:162–71.CrossRefPubMedPubMedCentralGoogle Scholar
  203. 203.
    Thurman JM, Lenderink AM, Royer PA, Coleman KE, Zhou J, Lambris JD, et al. C3a is required for the production of CXC chemokines by tubular epithelial cells after renal ishemia/reperfusion. J Immunol. 2007;178:1819–28. PubMed PMID: 17237432.CrossRefPubMedGoogle Scholar
  204. 204.
    Morgan BP. Regulation of the complement membrane attack pathway. Crit Rev Immunol. 1999;19:173–98. PubMed PMID: 10422598.CrossRefPubMedGoogle Scholar
  205. 205.
    Thurman JM, Scott Lucia M, Ljubanovic D, Michael Holers V. Acute tubular necrosis is characterized by activation of the alternative pathway of complement. Kidney Int. 2005;67:524–30.CrossRefPubMedGoogle Scholar
  206. 206.
    Brar JE, et al. Complement activation in the tubulointerstitium: Aki, ckd, and in between. Kidney International. 2014;86:663–6.CrossRefPubMedGoogle Scholar
  207. 207.
    McCullough JW, Renner B, Thurman JM. The role of the complement system in acute kidney injury. Semin Nephrol. 2013;33:543–56. PubMed PMID: 24161039.CrossRefPubMedGoogle Scholar
  208. 208.
    Pratt JR, Basheer SA, Sacks SH. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med. 2002;8:582–7. PubMed PMID: 12042808.CrossRefPubMedGoogle Scholar
  209. 209.
    Takada M, Nadeau KC, Shaw GD, Marquette KA, Tilney NL. The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand. J Clin Invest. 1997;99:2682–90. PubMed PMID: 9169498.CrossRefPubMedPubMedCentralGoogle Scholar
  210. 210.
    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):217–26. PubMed PMID: 16449793.CrossRefPubMedGoogle Scholar
  211. 211.
    Renner B, Coleman K, Goldberg R, Amura C, Holland-Neidermyer A, Pierce K, et al. The complement inhibitors Crry and factor H are critical for preventing autologous complement activation on renal tubular epithelial cells. J Immunol (Baltimore, Md: 1950). 2010;185:3086–94. PubMed PMID: 20675597.CrossRefGoogle Scholar
  212. 212.
    Thurman JM, Ljubanović D, Royer PA, Kraus DM, Molina H, Barry NP, et al. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. J Clin Invest. 2006;116:357–68. PubMed PMID: 16444293.CrossRefPubMedPubMedCentralGoogle Scholar
  213. 213.
    Bonventre JV. Complement and renal ischemia-reperfusion injury. Am J Kidney Dis. 2001;38:430–3.CrossRefPubMedGoogle Scholar
  214. 214.
    Elward K, Griffiths M, Mizuno M, Harris CL, Neal JW, Morgan BP, et al. CD46 plays a key role in tailoring innate immune recognition of apoptotic and necrotic cells. J Biol Chem. 2005;280:36342–54. PubMed PMID: 16087667.CrossRefPubMedGoogle Scholar
  215. 215.
    Isenman DE, Kells DI, Cooper NR, Müller-Eberhard HJ, Pangburn MK. Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties. Biochemistry. 1981;20:4458–67. PubMed PMID: 7284336.CrossRefPubMedGoogle Scholar
  216. 216.
    Mason J, Torhorst J, Welsch J. Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure. Kidney Int. 1984;26:283–93.CrossRefPubMedGoogle Scholar
  217. 217.
    Thurman JM, Ljubanovic D, Edelstein CL, Gilkeson GS, Holers VM. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol. 2003;170(3):1517–23. PubMed PMID: 12538716.CrossRefPubMedGoogle Scholar
  218. 218.
    Thurman JM, Holers VM. The central role of the alternative complement pathway in human disease. J Immunol. 2006;176(3):1305–10. ubMed PMID: 16424154.CrossRefPubMedGoogle Scholar
  219. 219.
    Zhou W, Farrar CA, Abe K, Pratt JR, Marsh JE, Wang Y, et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest. 2000;105:1363–71. PubMed PMID: 10811844.CrossRefPubMedPubMedCentralGoogle Scholar
  220. 220.
    De Vries B, Matthijsen RA, Wolfs TGAM, Van Bijnen AAJHM, Heeringa P, Buurman WA. Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and inflammation. Transplantation. 2003;75:375–82. PubMed PMID: 12589162.CrossRefPubMedGoogle Scholar
  221. 221.
    Faubel S, Ljubanovic D, Reznikov L, Somerset H, Dinarello CA, Edelstein CL. Caspase-1-deficient mice are protected against cisplatin-induced apoptosis and acute tubular necrosis. Kidney Int. 2004;66(6):2202–13. PubMed PMID: 15569309.CrossRefPubMedGoogle Scholar
  222. 222.
    Akcay A, Nguyen Q, Edelstein CL. Mediators of inflammation in acute kidney injury. Mediat Inflamm. 2009;2009:137072. PubMed PMID: 20182538. Pubmed Central PMCID: PMC2825552.CrossRefGoogle Scholar
  223. 223.
    Nechemia-Arbely Y, Barkan D, Pizov G, Shriki A, Rose-John S, Galun E, et al. IL-6/IL-6R axis plays a critical role in acute kidney injury. J Am Soc Nephrol. 2008;19(6):1106–15. PubMed PMID: 18337485. Pubmed Central PMCID: PMC2396933.CrossRefPubMedPubMedCentralGoogle Scholar
  224. 224.
    Melnikov VY, Ecder T, Fantuzzi G, Siegmund B, Lucia MS, Dinarello CA, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest. 2001;107(9):1145–52. PubMed PMID: 11342578. Pubmed Central PMCID: PMC209282.CrossRefPubMedPubMedCentralGoogle Scholar
  225. 225.
    Ramesh G, Reeves WB. TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest. 2002;110(6):835–42. PubMed PMID: 12235115. Pubmed Central PMCID: PMC151130.CrossRefPubMedPubMedCentralGoogle Scholar
  226. 226.
    Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, et al. Endotoxemic renal failure in mice: role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int. 2001;59(6):2243–9. PubMed PMID: 11380827.CrossRefPubMedGoogle Scholar
  227. 227.
    Adachi T, Sugiyama N, Yagita H, Yokoyama T. Renal atrophy after ischemia-reperfusion injury depends on massive tubular apoptosis induced by TNFalpha in the later phase. Med Mol Morphol. 2014;47(4):213–23. PubMed PMID: 24407718.CrossRefPubMedGoogle Scholar
  228. 228.
    Poon M, Megyesi J, Green RS, Zhang H, Rollins BJ, Safirstein R, et al. In vivo and in vitro inhibition of JE gene expression by glucocorticoids. J Biol Chem. 1991;266(33):22375–9. PubMed PMID: 1939262.PubMedGoogle Scholar
  229. 229.
    Oh DJ, Dursun B, He Z, Lu L, Hoke TS, Ljubanovic D, et al. Fractalkine receptor (CX3CR1) inhibition is protective against ischemic acute renal failure in mice. Am J Physiol Renal Physiol. 2008;294(1):F264–71. PubMed PMID: 18003857.CrossRefPubMedGoogle Scholar
  230. 230.
    Lu LH, Oh DJ, Dursun B, He Z, Hoke TS, Faubel S, et al. Increased macrophage infiltration and fractalkine expression in cisplatin-induced acute renal failure in mice. J Pharmacol Exp Ther. 2008;324(1):111–7. PubMed PMID: 17932247.CrossRefPubMedGoogle Scholar
  231. 231.
    Cugini D, Azzollini N, Gagliardini E, Cassis P, Bertini R, Colotta F, et al. Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion. Kidney Int. 2005;67(5):1753–61. PubMed PMID: 15840022.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • David A. Ferenbach
    • 1
    • 2
  • Eoin D. O’Sullivan
    • 1
    • 2
  • Joseph V. Bonventre
    • 3
    • 4
    • 5
  1. 1.MRC Centre of Inflammation ResearchUniversity of EdinburghEdinburghUK
  2. 2.Department of Renal MedicineRoyal Infirmary of EdinburghEdinburghUK
  3. 3.Renal Division and Engineering in Medicine Division, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Division of Health Sciences and TechnologyHarvard-Massachusetts Institute of TechnologyCambridgeUSA
  5. 5.Harvard Stem Cell InstituteCambridgeUSA

Personalised recommendations