Predictive Value Of Urinary Aquaporin 2 Rau Mob Raum Mob Raum Hauv Cov Neeg Mob Nrog Mob Decompensated Heart Failure

Abstract: Mob raum raug mob(AKI) feem ntau ntsib hauv cov neeg nrogmob plawv tsis ua hauj lwm decompensated(ADHF) thiab yog txuam nrognce morbiditythiabkev tuag.Kev tshawb pom ntxov ntawm cov zis biomarkerntawmmob raumtuaj yeem tso cai kuaj mob sai thiabtxhim kho cov txiaj ntsig. Qib ntawmurinary aquaporin 2 (UAQP2), uas tseem cuam tshuam nrog ntau yam kab mob raum, tau nce nrog ADHF. Peb tsom los txiav tximua UAQP2kwv yeesAKIhauv cov neeg mob nrog ADHF. Peb tau ua qhov kev soj ntsuam yav tom ntej hauv chav kho mob coronary (CCU) hauv tsev kho mob tertiary tsev kho mob hauv Taiwan. Cov tib neeg uas muaj ADHF tau txais mus rau CCU thaum lub Kaum Ib Hlis 2009 thiab Kaum Ib Hlis 2014 tau cuv npe, thiab tau sau cov ntshav thiab zis. AKI tau kuaj pom hauv 69 (36.5%) ntawm 189 tus neeg mob laus (lub hnub nyoog nruab nrab: 68 xyoo). Lub cheeb tsam nyob rau hauv lub receiver kev khiav hauj lwm yam ntxwv nkhaus (AUROC) ntawm biomarkers raug soj ntsuam los ntsuam xyuas qhov kev kuaj mob.zog rau AKI. Ob lub paj hlwb natriuretic peptide thiab UAQP2 tau pom tias tau txais AUROCs (0.759 thiab 0.795, feem). Kev sib xyaw ntawm cov cim muaj AUROC ntawm 0.802. UAQP2 is amuaj peev xwm biomarker ntawm AKIhauv CCU cov neeg mob nrog ADHF. Kev tshawb fawb ntxiv ntawm qhov tshiab biomarker yog xav tau.

YUAV UA LI CAS RAU CISTANCHE ua haujlwm rau cov neeg mob rau lub raum?

Ntsiab lus:mob raum mob; mob plawv tsis ua hauj lwm decompensated; chav kho mob coronary; tso zis aquaporin 2

1. Taw qhia

Mob raum mob (AKI)yog ib txwm muaj rau cov tib neeg uas muaj mob plawv tsis ua hauj lwm (ADHF), thiab ntau hom kab mob cardiorenal tau npaj rau xyoo 2008 [1]. Ntau tshaj 20% ntawm cov neeg mob ADHF tsim AKI thaum mus pw hauv tsev kho mob, thiab AKI hauv cov neeg mob no cuam tshuam nrog kev pheej hmoo ntawm kev tuag [2–4]. Qhov hnyav ntawm AKI kuj tseem cuam tshuam nrog qib ntawm ADHF. Txawm li cas los xij, kev kuaj mob ntawm AKI los ntawm kev siv cov txheej txheem creatinine yog qhov tsis zoo vim nws qhov ncua sij hawm 24-72 teev hauv qhov siab txij thaum pib [5]. Cov kws kho mob tuaj yeem siv cov kev ntsuas nephroprotective los txhim kho cov txiaj ntsig ntawm cov neeg mob nrog ADHF yog tias AKI tau lees paub ntxov. [6] Ntau lub biomarkers tau thov kom kuaj xyuas AKI hauv qhov xwm txheej no, xws li lub hlwb natriuretic peptide (BNP), cystatin C, neutrophil gelatinase-sociated lipocalin,lub raum raug mob molecule-1, proenkephalin, thiab tso zis TIMP-2 × IGFBP7 [7–13]. Txawm hais tias qee qhov biomarkers tau txais txiaj ntsig zoo thiab tau raug lees paub hauv ntau qhov kev sim tshuaj, kev sim ua haujlwm qeeb qeeb, tej zaum vim yog cov txiaj ntsig ntawm cov kev tshawb fawb biomarkers [14-16]. CovKab mob raum: Kev Txhim Kho Ntiaj Teb Cov Txheej Txheem Kev Sib Tham tau hais kom cov kev tshawb fawb tshiab ntsuas qhov kev kuaj mob, kev kho-qhia, lossis lub luag haujlwm prognostic ntawm biomarkers [16].

Aquaporin 2 (AQP2)yog ib tug dej channel tam sim no mas nyob rau hauv lub hauv paus ntsiab lus ntawm kev sau ducts. Nws yog tswj los ntawm arginine vasopressin (AVP) thiab yog lub luag haujlwm rau kev tswj cov zis concentration [17-19]. AVP khi rau AVP hom 2 (V2) receptor, ua rau apical trafficking ntawm intracellular AQP2 los ntawm cyclic-adenosine-monophosphate-dependent phosphorylation [20,21]. Hloov pauv, V2 receptor antagonist tolvaptan tiv thaiv AQP2 kev lag luam thiab txo cov zis osmolality [22]. Kwv yees li 3% ntawm AQP2 hauv lub raum yog tawm hauv cov zis; AQP2 hauv cov zis tuaj yeem suav tau tias yog qhov tsis muaj kev cuam tshuam ntawm kev sau cov kab ua haujlwm rau AVP [23,24]. Cov zis AQP2 tau nce ntau hauv ntau qhov kev kho mob, xws li lub plawv tsis ua haujlwm, qhov mob ntawm qhov tsis tsim nyog tso tawm ntawm cov tshuaj antidiuretic hormone, cirrhosis, thiab cev xeeb tub [25-28]. Tsis tas li ntawd, UAQP2 qib tau nce hauv ntshav qab zib nephropathy thiab yog qhov muaj peev xwm tsis muaj peev xwm biomarker hauv kev kwv yees theem kho mob [29]. Tsis tas li ntawd, kev hloov pauv hauv cov zis AQP2 tau pom nyob rau hauv ntau hom tsiaj, suav nrog ischemia-reperfusion (I/R), cisplatin-induced, thiab gentamicin-induced AKI tsiaj qauv [30–32]. Muab lub luag haujlwm kuaj pom muaj peev xwm ntawm AKI, qhov kev tshawb fawb no yog tsom rau kev txiav txim siab seb cov zis AQP2 tuaj yeem kwv yees AKI hauv cov neeg mob ADHF.

2. Cov ntaub ntawv thiab cov txheej txheem

Peb tau ua txoj kev tshawb fawb yav tom ntej, kev soj ntsuam hauv lub tsev kho mob coronary (CCU) ntawm 3700-txoj kev saib xyuas menyuam txaj txaj hauv Taiwan thaum lub Kaum Ib Hlis 2009 thiab Kaum Ib Hlis 2014. Cov neeg mob tau kuaj pom tias muaj ADHF tau cuv npe. Peb suav tag nrho ntawm 189 tus neeg mob thiab faib cov neeg sau npe rau hauv AKI thiab tsis yog AKI pawg. Peb tsis suav cov neeg mob uas muaj qhov ntsuas qhov ntsuas glomerular filtration rate (eGFR) ntawm<30 mL/min/1.73 m2, were receiving raum hloov kho, muaj hnub nyoog<18 years, or had reported any prior organ transplantation. No enrolled patients had been exposed to vasopressin V2 receptor antagonists such as tolvaptan during admission. The study protocol was approved by the local institutional review board (no. 201401993B0). We prospectively collected the following data: demographic characteristics, routine hemogram and biochemistry test results, and hospital outcomes. Biochemistry and hemogram values were measured by the central laboratory of Chang Gung Memorial Hospital. 

Kev kuaj mob ntawm ADHF yog raws li European Society of Cardiology cov qauv [33]. Txhua tus neeg mob tau txais kev kho mob tus qauv rau ADHF. Ob tus neeg mob AKI thiab cov neeg tsis yog AKI tau txais cov qauv kho mob rau ADHF raws li tus kws kho mob CCU qhov kev txiav txim siab. Peb tsom los txiav txim qhov kwv yees tus nqi ntawm UAQP2 rau AKI. Qhov txiaj ntsig tseem ceeb yog ib theem ntawm AKI hauv 7 hnub tom qab nkag mus rau CCU. AKI tau txhais tias yog qhov nce hauv SCr los ntawm Ntau dua lossis sib npaug rau 0.3 mg / dL hauv 48 h lossis nce hauv SCr rau ntau dua lossis sib npaug li 1.5 npaug ntawm qhov pib hauv 7 hnub, raws li Cov lus txhais hauv Kab Mob Raum: Txhim Kho Ntiaj Teb Kev Ua Tau Zoo (KDIGO)Clinical Practice Guidelines for Acute Kidney Injury. Qhov hnyav ntawm AKI kuj raug txiav txim raws li KDIGO cov lus qhia. Cov txiaj ntsig thib ob yog 180-hnub thiab 365- hnub tuag. Peb kuj tau soj ntsuam cov neeg koom nrog rau 12 lub hlis los ntawm kev tshuaj xyuas cov ntaub ntawv kho mob hauv hluav taws xob lossis kev sib tham hauv xov tooj.

Cov zis kuaj tau muab tso rau hauv cov hlab ntsha uas tsis muaj heparinized tam sim ntawd tom qab nkag mus rau hauv CCU. Cov qauv sau tau centrifuged ntawm 5000 × g rau 30 min ntawm 4 ◦C kom tshem tawm cov hlwb thiab cov khib nyiab. Cov supernatants paub meej tau muab rho tawm thiab muab khaws cia ntawm −80 ◦C kom txog rau thaum kev tshuaj xyuas ntxiv. UAQP2 tau ntsuas siv ELISA Cov Khoom Siv rau Aquaporin 2 (Cloud-clone Corp cov khoom naj npawb SEA580Hu, Katy, TX, USA). Cov txheej txheem xeem tau ua raws li cov chaw tsim khoom tshwj xeeb.

Kev hloov pauv tsis tu ncua (piv txwv li, hnub nyoog thiab cov ntaub ntawv kuaj) ntawm pawg AKI thiab tsis yog-AKI tau muab piv nrog cov qauv ywj pheej t-test. Cov biomarkers ntawm kev txaus siab (serum BNP, UAQP2, thiab UAQP2 / zis creatinine (UCr) tau muab piv nrog kev xeem Mann– Whitney U vim qhov tsis muaj qhov qub. UAQP2 thiab ntshav BNP thoob plaws AKI theem tau soj ntsuam siv Jonckheere-Terpstra kev sim Lub koom haum yog tween lub biomarkers ntawm kev txaus siab thiab kev pheej hmoo ntawm AKI tau tshawb xyuas los ntawm kev soj ntsuam kev rov qab los ntawm ntau qhov kev pheej hmoo ntawm AKI thiab HF tau kho Cov qauv sib txawv logistic regression, suav nrog hnub nyoog, poj niam txiv neej, ntshav qab zib, kub siab, txhais tau tias atrial siab, sab laug ventricular ejection feem (LVEF), hemoglobin, thiab lub hauv paus ntshav creatinine.

Lub cheeb tsam nyob rau hauv lub receiver operating yam ntxwv nkhaus (AUROC) yog siv los tshuaj xyuas lub peev xwm ntawm kev ntxub ntxaug ntawm biomarkers hauv kev kuaj mob AKI. Peb txuas ntxiv piv rau AUROC ntawm BNP ib leeg rau ntawm BNP ntxiv rau UAQP2 thiab ntawm BNP ntxiv rau UAQP2 / UCr. Tus qauv yuam kev ntawm AUROC tau suav nrog DeLong's nonparametric txoj kev. Cov txiaj ntsig sib xyaw ntawm AKI theem 3 thiab kev tuag hauv tsev kho mob kuj tau txheeb xyuas, ntxiv rau AKI theem 1-3. Thaum kawg, raws li kev pom zoo txiav tawm ntawm UAQP2 thiab UAQP2 / UCr txiav txim siab los ntawm Youden index, peb muab piv rau 180-hnub ciaj sia taus ntawm cov pab pawg siab dua thiab qis dua los ntawm kev siv cov ntawv teev npe. Qhov ob-tailed p-tus nqi tsawg dua 0.05 tau suav tias yog qhov tseem ceeb hauv peb txoj kev tshawb fawb. Peb siv SPSS 25 (IBM SPSS Inc, Chicago, IL, USA) rau kev txheeb xyuas cov ntaub ntawv.