title: Renalase protects against ischemic AKI.
abstract: Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.
authors: Department of Anesthesiology, Anesthesiology Research Laboratories, College of Physicians and Surgeons, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032-3784, USA. tl128@columbia.edu
authors: H Thomas
authors: HT
authors: Lee
authors: Joo Yun
authors: JY
authors: Kim
authors: Mihwa
authors: M
authors: Kim
authors: Peili
authors: P
authors: Wang
authors: Lieqi
authors: L
authors: Tang
authors: Sara
authors: S
authors: Baroni
authors: Vivette D
authors: VD
authors: D'Agati
authors: Gary V
authors: GV
authors: Desir
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D000317:Adrenergic alpha-Antagonists; D018836:Inflammation Mediators; D012333:RNA, Messenger; D011994:Recombinant Proteins; D008995:Monoamine Oxidase; C521557:renalase; D009638:Norepinephrine; D010646:Phentolamine
references: J Clin Invest. 2005 May;115(5):1275-80
references: 15841207
references: Acta Clin Belg. 2007;62 Suppl 2:326-31
references: 18283993
references: Curr Opin Nephrol Hypertens. 2007 Jul;16(4):373-8
references: 17565281
references: PLoS One. 2011 Jan 31;6(1):e14633
references: 21297953
references: Biochim Biophys Acta. 2004 Aug 4;1689(3):212-8
references: 15276647
references: Kidney Int. 2011 Apr;79(8):853-60
references: 21178975
references: Kidney Int. 2009 Aug;76(4):366-70
references: 19471322
references: J Am Heart Assoc. 2012 Aug;1(4):e002634
references: 23130169
references: Microvasc Res. 2009 Jan;77(1):8-12
references: 18929580
references: Biochim Biophys Acta. 2000 Dec 15;1535(1):36-44
references: 11113629
references: Pediatr Nephrol. 2012 May;27(5):719-25
references: 21424526
references: Eur J Pharmacol. 2003 Nov 28;481(2-3):241-8
references: 14642792
references: Transplantation. 1983 Mar;35(3):198-204
references: 6340272
references: Curr Opin Nephrol Hypertens. 2008 Mar;17(2):181-5
references: 18277152
references: J Pharmacol Exp Ther. 2011 Aug;338(2):648-57
references: 21571945
references: Biochim Biophys Acta. 2001 Jul 27;1537(1):49-57
references: 11476962
references: Am J Physiol Gastrointest Liver Physiol. 2000 Dec;279(6):G1274-81
references: 11093951
references: Circulation. 2008 Mar 11;117(10):1277-82
references: 18299506
references: Contrib Nephrol. 2010;165:153-158
references: 20427965
references: Semin Dial. 2003 Nov-Dec;16(6):438-46
references: 14629602
references: J Am Soc Nephrol. 2004 Jan;15(1):102-11
references: 14694162
references: Clin J Am Soc Nephrol. 2007 Mar;2(2):356-65
references: 17699435
references: J Am Soc Hypertens. 2007 Mar-Apr;1(2):99-103
references: 20409839
references: Am J Nephrol. 2010;31(4):353-62
references: 20234131
references: J Am Soc Nephrol. 2009 May;20(5):933-9
references: 18799718
references: J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):412-6
references: 22626958
references: PLoS One. 2009;4(5):e5504
references: 19430535
references: Transplantation. 2000 Mar 15;69(5):959-63
references: 10755557
references: Best Pract Res Clin Anaesthesiol. 2008 Mar;22(1):193-208
references: 18494397
references: Exp Ther Med. 2012 Sep;4(3):493-496
references: 23181124
references: J Neural Transm (Vienna). 2007;114(6):775-6
references: 17385068
references: Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G1014-21
references: 11557522
references: J Cardiothorac Vasc Anesth. 2004 Aug;18(4):442-5
references: 15365924
references: Int J Mol Med. 2000 May;5(5):457-65
references: 10762647
references: Scand J Clin Lab Invest. 1965;17(4):381-7
references: 5838275
references: J Am Soc Nephrol. 2005 Nov;16(11):3365-70
references: 16177006
references: Am J Physiol Renal Physiol. 2004 Feb;286(2):F298-306
references: 14600029
references: Kidney Int. 2009 Apr;75(8):809-23
references: 19190680
references: Lab Invest. 2011 Jan;91(1):63-84
references: 20697374
references: Am J Physiol Renal Physiol. 2010 Aug;299(2):F347-58
references: 20484296
references: Curr Opin Nephrol Hypertens. 2011 Jan;20(1):31-6
references: 21099685