Predictive Value Of Urinary Aquaporin 2 Rau Mob Raum Mob Raum Hauv Cov Neeg Mob Nrog Mob Decompensated Heart Failure Ⅱ
May 08, 2024
3. Cov txiaj ntsig
3.1. Cov yam ntxwv ntawm tus neeg mob
Zuag qhia tag nrho, 189 tus neeg mob laus (129 txiv neej thiab 60 poj niam) tau tshawb xyuas.AKItau kuaj pom hauv 69 (36.5%) cov neeg mob. Piv nrog rau cov neeg mob hauv pab pawg tsis-AKI, cov neeg hauv pawg AKI muaj cov yam ntxwv hauv qab no: lawv laus dua, tsis tshua muaj LVEF thiab yuav muaj ntau dua.mob raum mob(CKD) los yog kub siab, thiab muaj cov ntsiab lus siab duantshav creatinine, qishemoglobin, thiabntau dua cov poov tshuaj(p < 0.05). Hais txog biomarkers ntawm kev txaus siab, qhov nruab nrabntshav BNP qib1210 pg / mL thiab 479 pg / mL, thiab qhov nruab nrab UAQP2 qib yog 61.5 ng / mL thiab 30.9 ng / mL, feem,AKI thiab tsis-AKIpab pawg (p < {{0}} 001). Txhawm rau them nyiaj rau qhov sib txawv ntawm cov zis dilution, cov zis UAQP2 qhov tseem ceeb tau hloov kho raws li UCr. Qhov nruab nrab UAQP2 / Cr qib hauv AKI thiab cov tsis-AKI pawg yog 1.09 fmol / mg thiab 0.35 fmol / mg, raws li (p <0.001; Table 1). Tsis tas li ntawd, theem ntawm cov ntshav BNP thiab UAQP2 nce nrog AKI qhov hnyav (Daim duab 1).
YUAV UA LI CAS RAU CISTANCHE ua haujlwm rau cov neeg mob rau lub raum?
Table 1. Cov yam ntxwv tseem ceeb ntawm cov neeg mob tau txais los ntawm lub plawv tsis ua haujlwm nrog lossis tsis muaj AKI.
AKI,mob raum mob; BNP,paj hlwb natriuretic peptide; Hb,hemoglobin; LVEF, sab laug ventricular ejection feem; MAP, txhais tau tias arterial siab; UAQP2, tso zis tawm ntawm aquaporin 2; UCr,tso zis creatinine; WBC, suav cov qe ntshav dawb. Cov ntaub ntawv txuas ntxiv tau nthuav tawm raws li qhov txhais tau tias ± tus qauv sib txawv lossis nruab nrab (25th, 75th feem pua).
Daim duab 1. Qib ntshav BNP (a) thiab zis AQP2 (b) hla KDIGO theem. Cov ntawv luv: AQP2, aquaporin 2; BNP, paj hlwb natriuretic peptide; KDIGO, Kab mob raum: Txhim kho cov txiaj ntsig thoob ntiaj teb. Cov ntawv luv: BNP, hlwb natriuretic peptide; UAQP2, tso zis tawm ntawm aquaporin 2; UCr, tso zis creatinine. Daim duab 1. Qib ntshav BNP (a) thiab zis AQP2 (b) hla KDIGO theem. Cov ntawv luv: AQP2, aquaporin 2; BNP, paj hlwb natriuretic peptide; KDIGO, Kab mob raum: Txhim kho cov txiaj ntsig thoob ntiaj teb. Cov ntawv luv: BNP, hlwb natriuretic peptide; UAQP2, tso zis tawm ntawm aquaporin 2; UCr, tso zis creatinine.
Kwv yees li ib nrab ntawm cov neeg mob AKI muaj theem 2 lossis 3 AKI (Table 2). Thaum kawg, xya (11.1%) ntawm AKI cov neeg mob tau txais hemodialysis. Tag nrho ntawm 24 tus neeg mob tau txais txiaj ntsig ntawm AKI thiab kev tuag hauv tsev kho mob. Cov neeg mob hauv pawg AKI tau nyob hauv tsev kho mob ntev dua. Cov neeg mob kuj nyiam muaj kev tuag hauv tsev kho mob ntau dua, kev nyeem ntawv siab dua hauv 180 hnub, thiab kev nyeem ntawv siab dua hauv 365 hnub dua li lawv cov neeg tsis yog AKI, txawm hais tias qhov sib txawv tsis tseem ceeb (Table 2).
Table 2. Cov txiaj ntsig hauv tsev kho mob thiab tus nqi nkag ntawm cov neeg mob tau txais vim yog lub plawv tsis ua haujlwm nrog lossis tsis muaj AKI.
3.2. Association of Serum BNP, UAQP2, and the Risk of AKI
Thaum paub tias muaj kev pheej hmoo ntawm AKI tsis raug kho rau, cov ntshav siab dua BNP, UAQP2, thiab ua haujlwm zoo UAQP2 tau cuam tshuam nrog kev pheej hmoo ntawm AKI (Model 1 ntawm Table 3). Cov biomarkers no tseem muaj feem cuam tshuam nrog kev pheej hmoo ntawm AKI txawm tias muaj kev hloov kho ntxiv rau tag nrho covariates (Model 5 ntawm Table 3). Los ntawm qhov sib txawv, kev koom tes ntawm peb lub biomarkers thiab qhov kev pheej hmoo ntawm cov txiaj ntsig sib xyaw (AKI theem 3 thiab kev tuag hauv tsev kho mob) tsis tseem ceeb nrog kev hloov kho rau covariates.
Table 3. Association of BNP, UAQP2, thiab UAQP2/Cr nrog rau kev pheej hmoo ntawm AKI thiab kev sib xyaw ntawm AKI theem 3 thiab kev tuag hauv tsev kho mob
Table 4. Kev ntxub ntxaug ntawm AKI thiab qhov sib xyaw ntawm AKI theem 3 thiab kev tuag hauv tsev kho mob: tus neeg txais kev khiav hauj lwm tus yam ntxwv nkhaus tsom xam ntawm biomarkers ntawm lub plawv tsis ua hauj lwm thiab lub raum tsis ua hauj lwm.
3.4. 180-Hnub Ciaj sia nyob tus nqi siab- thiab qis-Biomarker Subgroups
The optimal cutoffs of UAQP2 and normalized UAQP2 were >35.3 ng/mL and >0.83 fmol/mg, raws li (Table 4). Txawm li cas los xij, txawm tias UAQP2 tau zoo li qub lossis tsis yog, tsis muaj qhov sib txawv tseem ceeb hauv 180-hnub ciaj sia taus tus nqi ntawm qhov siab piv rau cov pab pawg qis tau pom (Daim duab 3).
Daim duab 3. Cov neeg tuag coob coob thaum lub sij hawm 180-ib hnub tom qab cov neeg mob, nrog rau stratification ntawm qhov pom kev txiav tawm ntawm UAQP2 (a) thiab UAQP2/UCr (b). Cov ntawv luv: UAQP2, tso zis ntawm aquaporin 2; UCr, tso zis creatinine.
4. Kev sib tham
Rau peb txoj kev paub, qhov no yog thawj txoj kev tshawb fawb los ntsuas UAQP2 qib hauv AKI ntawm CCU cov neeg mob nrog ADHF. Txawm hais tias lawv tau normalized los ntawm UCr, UAQP2 qib tau nce siab dua hauv cov neeg uas muaj AKI dua li cov tsis muaj. Tsis tas li ntawd, UAQP2 qib nce nrog AKI theem. Txawm tias tom qab hnub nyoog, poj niam txiv neej, ntshav qab zib mellitus, kub siab, txhais tau tias arterial siab, LVEF, thiab lub hauv paus creatinine raug kho, qib UAQP2 yog txuam nrog kev pheej hmoo ntawm AKI. UAQP2 kuj tau ua kom pom kev ncaj ncees kev ntxub ntxaug AKI thiab cov txiaj ntsig sib xyaw ntawm theem 3 AKI thiab kev tuag hauv tsev kho mob. Peb qhov kev tshawb pom txhawb nqa qhov kev kuaj mob ntawm UAQP2 hauv AKI rau cov tib neeg uas muaj ADHF.
Neurohormonal activation plays lub luag haujlwm tseem ceeb hauv cardiorenal syndrome. Raws li lub plawv tsis ua hauj lwm hnyav dua, ntshav siab txo qis thiab lub raum perfusion zuj zus, ua rau baroreceptor thiab renin-angiotensin-aldosterone system ua kom ua haujlwm, raws li [34]. Neuhormonal activation ntxiv zuj zus ntxiv lawm ua rau lub plawv tsis ua haujlwm, uas ua rau muaj kev cuam tshuam ntxiv ntawm lub hom phiaj ntawm lub cev, ua rau lub voj voog tsis zoo [35]. Ntawm txoj kev ua haujlwm neurohormonal nyuaj, AVP ua lub luag haujlwm tseem ceeb hauv plawv tsis ua haujlwm [36]. Hauv cov neeg mob uas muaj lub plawv tsis ua haujlwm, qhov txo qis hauv cov ntshav ntws zoo ua rau muaj qhov ua rau muaj kev nce ntxiv [37,38]. Nyob rau hauv lub raum, AVP khi rau V2 receptor, ua rau muaj zog ntau lawm ntawm cyclic adenosine monophosphate, ntxiv ua rau AQP2 phosphorylation ntawm protein kinase A thiab thauj AQP2 mus rau apical membrane ntawm lub hauv paus hlwb [39,40]. AVP-mediated water retention thiab dilutional hyponatremia yog muaj nyob rau hauv cov neeg mob plawv tsis ua hauj lwm thiab tom qab phais plawv [41,42]. Qhov tseem ceeb, qib UAQP2 zoo sib xws nrog AQP2 hauv lub raum [23,24]. Peb qhov kev tshawb pom tau ua raws li cov kev xav tam sim no hais txog lub luag haujlwm pathophysiological ntawm AVP hauv cardiorenal syndrome thiab txhawb nqa tus nqi kuaj mob ntawm UAQP2 rau kev kuaj AKI hauv cov neeg mob ADHF.
AKI feem ntau tshwm sim hauv cov tib neeg uas muaj ADHF, thiab ib txwm kuaj mob ntawm AKI los ntawm txoj kev creatinine raug txwv los ntawm nws qhov ncua sij hawm 24-72 teev txij thaum pib mus txog qhov siab [13]. Cov kev tshawb fawb yav dhau los kuj tau txhawb nqa kev siv biomarkers los txhim kho kev kuaj mob thiab kev kwv yees ntawm AKI hauv cov neeg mob hnyav [43,44]. Cov kws kho mob tuaj yeem siv cov kev ntsuas nephroprotective los txhim kho cov txiaj ntsig ntawm tus neeg mob yog tias AKI tau lees paub ntxov [6]. Txawm hais tias qee tus kws tshaj lij tau qhia tsis ntseeg txog kev siv biomarkers txhawm rau kuaj AKI hauv ADHF cov neeg mob vim lawv qhov tsis sib xws, qhov kev tshawb pom tam sim no ntawm UAQP2 nce hauv AKI ntawm cov neeg mob plawv tsis ua haujlwm tau cog lus vim tias nws lub luag haujlwm kho tau zoo. Tam sim no, V2 receptor antagonists xws li tolvaptan yog muag thiab siv rau cov neeg mob uas muaj mob xws li lub plawv tsis ua hauj lwm refractory mus rau cov pa diuretics [45]. Kev tshawb fawb tsis ntev los no los ntawm Imamura et al. thov siv UAQP2 rau kev kwv yees ntawm kev teb rau tolvaptan hauv cov neeg mob uas muaj lub plawv tsis ua hauj lwm decompensated [46]. Nyob rau hauv ib qho kev khaws cia khaws cia, cov ntshav AVP txhawb nqa AQP2 phosphorylation thiab thauj mus rau apical membrane ntawm lub hauv paus tseem ceeb, thiab UAQP2 tuaj yeem siv los ua cov khoom siv biomarker rau cov kav dej sib sau [46]. Los ntawm qhov sib txawv, UAQP2 yuav luag tsis pom nyob rau hauv cov neeg mob tsis teb rau kev kho mob tolvaptan, xws li cov neeg mob uas muaj CKD siab lossis mob ntshav qab zib nephropathy, tejzaum nws yog vim kev khaws cov duct ua haujlwm tsis zoo [46–49]. Ntxiv mus, txoj kev tshawb fawb tsis ntev los no kuj tau hais txog kev hloov pauv hauv UAQP2 uas tuaj yeem siv los kwv yees cov lus teb tolvaptan hauv cov neeg mob uas muaj tus kab mob autosomal dominant polycystic raum [50]. Peb qhov kev tshawb pom ntawm qib UAQP2 nce ntxiv hauv AKI cov neeg mob nrog ADHF tuaj yeem pab txheeb xyuas tus neeg sib tw ua tau rau cov neeg mob teb rau kev kho tolvaptan. Tsis tas li ntawd, qhov kev nyab xeeb ntawm tolvaptan tau txais txiaj ntsig zoo, thiab cov neeg mob tsuas muaj kev phiv me me, xws li nqhis dej thiab lub qhov ncauj qhuav [51]. Kev tshawb nrhiav ntxiv yog xav tau los ntsuas kev siv UAQP2-kev qhia tolvaptan kho hauv ADHF cov neeg mob nrog AKI.
Kev nce qib UAQP2 hauv ADHF-induced AKI tej zaum yuav tsis yog thoob plaws hauv txhua qhov xwm txheej AKI. Kev txo qis hauv exosomal UAQP2 qib tau ntsuas hauv ntau tus tsiaj qauv ntawm AKI, suav nrog I / R, lipopolysaccharide (LPS)-induced, cisplatin-induced, thiab gentamicin-induced raum raug mob [30–32,39,52]. Asvapromtada et al. tau tshaj tawm qhov txo qis ntawm exosome UAQP2 thaum lub sij hawm hnyav AKI induced los ntawm I/R. Kev lag luam apical ntawm AQP2 hauv lub hauv paus tseem ceeb ntawm tes kuj tseem txo qis hauv I / R-vim raum raug mob. Tsis tas li ntawd, nyob rau hauv unilateral I / R AKI nas, txo cov zis osmolality thiab nce zis ntim tau raug tshaj tawm, qhia tias muaj qhov tsis zoo ntawm cov zis hnyav [30]. Tsis tas li ntawd, hauv LPS-induced AKI, kev qhia ntawm AQP2 kuj tseem txo qis txawm tias muaj kev nce qib hauv cov ntshav AVP [53]. Ib qho kev piav qhia txog qhov sib txawv ntawm UAQP2 qib yuav yog qhov sib txawv ntawm pathophysiology ntawm AKI; AKI yog ib qho mob uas muaj ntau yam sib txawv, thiab cov qauv AKI sib txawv muaj cov txheej txheem sib txawv ntawm lub raum raug mob. Piv txwv li, AVP ua lub luag haujlwm tseem ceeb hauv pathophysiology ntawm ADHF-txog AKI tab sis tsawg dua li lwm hom AKI. Hauv unilateral I/R AKI, ib qho endothelin{19}} nce tuaj yeem cuam tshuam AVP-vim dej permeability ntawm endothelin hom B receptors [30,54]. Kev nrawm nrawm ntawm AQP2 protein tau npaj rau LPS-induced AKI [53]. Lwm qhov kev piav qhia yuav yog lub sijhawm sib txawv ntawm qhov ntsuas ntawm UAQP2 txheeb ze rau qhov pib tshwm sim. Peb ntsuas UAQP2 thaum cov neeg mob tau mus rau CCU, qhov txo qis UAQP2 qib yuav raug pom nyob rau hnub 7 hauv tus qauv I / R rat ob sab. Kev ntsuas ntsuas ntawm UAQP2 hauv cov neeg mob nrog ADHF tuaj yeem muab kev pom ntau dua. Tsis zoo li cov kev tshawb fawb yav dhau los, uas ntsuas exosomal UAQP2, peb tau txheeb xyuas tag nrho UAQP2 hauv txoj kev tshawb no. AQP2 muaj nyob rau hauv ob qho tib si ib daim ntawv soluble thiab daim nyias nyias nyob rau hauv cov zis, thiab UAQP2 feem ntau nyob rau hauv lub low-density exosome [55]. UAQP2 hauv exosome yog li proportional rau UAQP2 qib tag nrho [20,55]. Zoo ib yam li UAQP2 soluble, qib exosomal UAQP2 muaj feem cuam tshuam nrog rau lub raum AQP2 qib [56]. ELISA tau siv hauv peb txoj kev tshawb fawb los ntsuas UAQP2, uas ntsuas ob qho tib si exosomal thiab soluble cov ntaub ntawv ntawm UAQP2 nrog kev ua tau zoo [57]. Txawm hais tias kev ntsuas exosomal UAQP2 tuaj yeem yog tus neeg sib tw zoo, txoj kev zoo tshaj plaws rau kev cais exosomes tseem sib cav [58]. Yuav tsum tau kawm ntxiv.
Peb txoj kev tshawb fawb muaj ntau yam kev txwv. Ua ntej, peb ntsuas UAQP2 tsuas yog ib zaug los kwv yees AKI hauv cov neeg mob ADHF. Kev ntsuas kev ntsuas ntawm biomarkers tuaj yeem cuam tshuam zoo rau lub raum raug mob thiab txhim kho lub zog kwv yees. Tsis tas li ntawd, plasma AVP qib tsis muaj nyob hauv peb txoj kev tshawb fawb. Qhov thib ob, ob qho tib si lub luag haujlwm thiab kev qhia ntawm UAQP2 hauv AKI nrog ADHF xav tau kev tshawb nrhiav ntxiv. Lub tshuab tso zis tso zis ntawm AQP2 tseem tsis to taub. Kev ua qauv tsiaj ntxiv tuaj yeem pab txhawm rau txheeb xyuas qhov tseeb thiab kev siv ntawm UAQP2 hauv ADHF nrog AKI. Thib peb, urinary exosomes tsis raug soj ntsuam hauv peb txoj kev tshawb fawb vim muaj kev txwv tsis pub siv. Thaum kawg, cov kev sim yav tom ntej ntxiv tau lees paub los tshawb txog kev siv UAQP2 rau AKI, muab cov qauv me me thiab kev soj ntsuam ntawm peb txoj kev tshawb fawb.
5. Cov lus xaus
Hauv cov ntsiab lus, UAQP2 qhia tau tias muaj kev ntxub ntxaug rau kev tshawb pom ntxov ntawm AKI hauv cov neeg mob ADHF, nrog rau cov ntshav BNP. Tsis tas li ntawd, kev sib xyaw ua ke ntawm ob lub cim tuaj yeem ua ib qho tshiab, tsis muaj kab mob biomarker kom sib txawv AKI. Kev sib xyaw ua ke muaj qhov siab tshaj AUROC; Yog li, nws muaj peev xwm ua kom paub qhov tseeb ntawm AKI. Kev tshawb fawb ntxiv yog xav tau los ntsuas qhov kev sib raug zoo ntawm qib UAQP2 thiab tolvaptan teb hauv AKI rau cov neeg mob ADHF.
Sau Kev Koom Tes: Kev Tsim Nyog, C.-HC thiab Y.-CC; methodology, C.-HC thiab Y.-CC; software, M.-JC; validation, GK thiab C.-CL; kev soj ntsuam, M.-JC, GK thiab C.-CL; kev tshawb nrhiav, P.-CF thiab C.-HC; cov peev txheej, M.-JC, C.-HC thiab Y.-CC; cov ntaub ntawv curation, M.-JC; kev sau ntawv-kev npaj ua ntej, M.-JC; sau-saib thiab kho, M.-JC thiab C.-HC; kev pom, C.-HC; kev saib xyuas, C.-HC; kev tswj xyuas qhov project, C.-HC; Kev nrhiav nyiaj txiag, C.-HC thiab M.-JC Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Cov Nyiaj Txiag: Txoj kev kawm no tau txais kev txhawb nqa los ntawm Ministry of Science thiab Technology thiab Chang Gung Memorial Hospital Research Program (NSC 103-2314-B-182A-040, 103-2314-B{ {4}}A-018- MY3, CORPG3J0591 thiab CORPG5H0081).
Institutional Review Board Statement: Txoj kev tshawb no tau ua raws li cov lus qhia ntawm Kev Tshaj Tawm ntawm Helsinki thiab pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm Chang Gung Memorial Tsev Kho Mob. (no. 201401993B0, pom zoo rau 6 Lub Ob Hlis 2017).
Cov Lus Qhia Txog Kev Pom Zoo: Cov ntaub ntawv pom zoo tau txais los ntawm txhua tus neeg koom nrog hauv txoj kev kawm.
Cov Lus Qhia Txog Cov Ntaub Ntawv: Cov ntaub ntawv qhia hauv qhov kev tshawb fawb no muaj nyob rau ntawm kev thov los ntawm tus kws sau ntawv. Cov ntaub ntawv tsis muaj nyob rau pej xeem vim muaj kev txwv tsis pub lwm tus paub / kev coj ncaj ncees.
Kev lees paub: Cov kws sau ntawv ua tsaug rau Alfred Hsing-Fen Lin thiab Ben Yu-Lin Chou rau lawv qhov kev pab cuam hauv kev txheeb cais.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
Cov ntaub ntawv
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