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1、Early biomarkers for diagnosis of postoperative acute renal failure 早期生物標記診斷術後急性腎臟衰竭早期生物標記診斷術後急性腎臟衰竭楊楊 光光 華華Devarajan P (2019) Curr Opin Pediatr Metabolic consequences of acute IRI to kidney tubule cells SensitivitySpeedSimple workflowComprehensive profiles High multi-plexityThe characteristic of bi
2、omarkerGoal1.Develop suitable monitoring system via biomarkers from NTUH SICU ARF databank.2.Identify the role of AKI biomarkers among injury, protection or repair. The animal model of ischemia-reperfusion injury for AKI40 min36122448 (hr)0ShamThe serum creatinine from post-operative ratsSerum creat
3、inine measurements obtained at various time points post-cardiac surgery from NSARF databankUrine netrin-1 from 9 AKI patients in NSARF databank 1 2 3 4 5 6 7 8 9 10 11 12 13Netrin-1 in urine collected from 1-2: normal health volunteers, 3-10: postoperative patients without acute kidney injury (AKI),
4、 11-13: postoperative patients with AKI. 40 mg creatinine for each human sample was subjected to Western blot analysis of Anti-netrin-1 Ab.Neogenin: One receptor, many functionsNicole and Brian (2019) The international journal of biochemistry & cell biology RGMc = Hemojuvelin (HJV), Hemochromatosis
5、type 2 (HFE2)Ivana DD et al., (2019) JCITranscriptional regulation of hepcidin by the BMP/Smad pathway The up-regulation of hepcidin in these segments of the nephron after renal ischemia leads to a down-regulation of the ferroportin exporter, preventing the further release of free iron into tissues
6、and resulting perpetuation of tubular injury. Modified from Douglas BK(2021) BMC Medical GenomicsOverview of the roles of hepcidin and NGAL after IRI Time course of Netrin-1, HJV, co-receptor Neogenin and Pendrin protein expression in rat kidney after I/R injury 0 3 3 6 12 12 24 24 (hr) HemojevelinN
7、etrin-1NeogeninActinShamAfter I/R injuryPendrinMW: 85.73 kDaPendrin, is an ion exchanger found in the cortical collecting duct, thyroid gland and inner ear. An apical Cl-/HCO3- exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involv
8、ed in extracellular fluid volume regulation.Sham 3 6 12-112-2 24-124-2 48-1 48-2 (hr)WB: Urinary HJV15% SDS-PAGECBR stainingUrinary HJV from rat after IR-InjuryAfter IRIUrinary HJV after 24 hr post-operation from NSARF databank Urine ARF RIFLE ARF With dialysisRenal recovery轉出入deathNameAgeMale(M=1)手
9、術時間術式CAD=1Valve=2CABG+Valve=3Valve+Other=4Aorta diseasr=5OTHER=6Aortic Clamp time(min)Total bypass time(min)24hr total urineyes=1(7day) Cr.=1U=2 yes=1 yes=1 yes=1林X鐘 74y1235 O.P.C.A.B 1 79 113 2564楊X龍 59y1240 M.V.R. 2 135 165 1495 潘X鑾 72y2465 O.P.C.A.B 1 0 101 1470 1 20 1 0趙X福 57y1394 A.V.R. 2 99 177 1415 1 10 1 0劉XX霞 60y2320 M.V.R. 2 78 119 1930 林 楊 潘 趙 劉HJVWB: 1st Anti-HJV pAb15% SDS-PAGEConclusion1.Urinary netrin-1 is an early diagnostic biomarker of AKI in post-cardiac surgery patients.2.Hemojuvelin may be a potential biomarker involved in iron homeostasis after IRI.
