Deoxycholic Acid Thiab Risks Ntawm Cardiovascular Events, ESKD, Thiab Mortality hauv CKD: Txoj Kev Kawm CRIC
Nov 03, 2023
Lub ntsiab lus & Lub Hom Phiaj:Kev nce qib ntawm deoxycholic acid(DCA) cuam tshuam nrog cov txiaj ntsig tsis zoo thiab tuaj yeem ua rau vascular calcification hauv cov neeg mobmob raum mob(CKD). Peb tau soj ntsuam qhov kev xav tias kev nce qib ntawm DCA tau cuam tshuam nrog kev pheej hmoo ntxiv ntawmkab mob plawv, CKD kev nce qib, thiab kev tuag hauv cov neeg mob CKD.
Kawm Design: Prospectivekev soj ntsuam kev tshawb fawb.
Kev teeb tsa & Cov neeg koom nrog: Peb suav nrog 3,147 Tus Neeg Mob Lub Raum Tsis Txaus Siab Kev Tshawb Fawb Kev Kawm uas tau yoo mov qib DCA. Lub hnub nyoog nruab nrab yog 59 ± 11 xyoo, 45.3% yog poj niam, 40.6% yog neeg Asmeskas Asmeskas, thiab qhov kwv yees kwv yees glomerular pom tus nqi yog 42.5 ± 16.0 mL / min / 1.73 m2 .
Tus kwv yees: Kev yoo mov DCA qib hauvChronic Renal InsufficiencyCov neeg koom nrog kev tshawb fawb.
Cov txiaj ntsig: Kev pheej hmoo ntawm atherosclerotic thiab lub plawv tsis ua haujlwm,kab mob raum kawg(ESKD), thiabtag nrho-ua rau tuag.
Txoj Kev Tshawb Fawb: Peb siv Tobit regression los txheeb xyuas cov kev kwv yees ntawm qib DCA. Peb siv Cox regression los tshuaj xyuas qhov kev sib koom ua ke ntawm kev yoo mov DCA qib thiab cov txiaj ntsig kho mob.
Cov txiaj ntsig: Cov kev kwv yees muaj zog tshaj plaws ntawm qib siab DCA hauv cov qauv hloov kho tau nce hnub nyoog thiab tsis siv cov statins. Cov kev sib koom ua ke ntawm cov log-transformed DCA qib thiab cov txiaj ntsig kev kho mob tsis yog linear. Tom qab hloov kho, DCA qib siab tshaj qhov nruab nrab ntawm nws tus kheej cuam tshuam nrog kev pheej hmoo siab dua ntawm ESKD (HR, 2.67; 95% CI, 1.51-4.74) thiab tag nrho-ua rau kev tuag (HR, 2.13; 95% CI, 1 . 25-3.64). DCA qib siab tshaj qhov nruab nrab tsis cuam tshuam nrog cov xwm txheej atherosclerotic thiab lub plawv tsis ua haujlwm, thiab DCA qib qis dua qhov nruab nrab tsis cuam tshuam nrog cov txiaj ntsig kho mob.
Kev txwv: Peb tsis tuaj yeem ntsuas DCA longitudinally lossis hauv cov zis los yog quav, thiab peb tsis tuaj yeem ntsuas lwm cov kua tsib acids. Peb kuj tsis tuaj yeem ntsuas ntau yam uas cuam tshuam rau qib DCA.
Cov lus xaus: Hauv 3,147 tus neeg koom nrog CKD theem 2-4, DCA qib siab tshaj qhov nruab nrab yog ntawm nws tus kheej
NYEEM NTXIV RAU HAUV PAUS TSEEM CEEB NTAWM CISTANCHE FOR KIDNEY
Cov neeg nrogmob raum mob(CKD) muaj qhov nce ntxiv ntawm cov kab mob plawv (CVD) thiab muaj kev pheej hmoo tuag ntau dua piv nrog cov pej xeem.1,2 Nrog rau lub raum tsis ua haujlwm, kev hloov pauv hauv cov metabolism hauv kev loj hlob. Tib neeg kev tshawb fawb qhia tias nyob rau hauvCKD, theem ntawm tag nrho cov kua tsib acids nce, tejzaum nws yog vim li cas ntawm lub siab ntau lawm, nce efflux los ntawm hepatocytes, los yog txo lub raum excretion.3-5 Qhov feem ntawm cov kua tsib acids, uas yog tsim los ntawm plab hnyuv kab mob los ntawm cov thawj bile acids, kuj nce. , tej zaum yuav yog vim qhov hloov pauv plab microbiome hauv cov neeg mob CKD.6,7 Muab cov kua tsib acids muaj lub luag haujlwm tseem ceeb ntxiv rau kev pabcuam kev zom zaub mov, suav nrog kev hloov kho mob, kev tswj hwm kev siv hluav taws xob thiab cov metabolism, thiab cuam tshuam rau kev tiv thaiv kev ua haujlwm, kua tsib acid dysregulation hauv CKD. tej zaum yuav muaj cov teebmeem tsis zoo.
Deoxycholic acid (DCA) yog cov kua tsib thib ob muab tau los ntawm cholic acid, thawj cov kua tsib kua qaub, thiab cov kev tshawb fawb qhia tias DCA qib tau nce siab hauv CKD.3,8,9 DCA tau cuam tshuam nrog ntau cov teebmeem ntawm cov cellular, xws li Raws li kev mob thiab kev tiv thaiv kab mob tsis zoo, thiab muaj feem cuam tshuam rau cov kab mob, xws li dyslipidemia thiab txo qis insulin rhiab heev. nrog CKD tej zaum yuav muaj kev cuam tshuam tsis zoo rau lub plawv thiab lub raum kev noj qab haus huv. Txhawm rau tshuaj xyuas cov kev sib koom ua ke ntawm DCA qib thiab cov txiaj ntsig kev kho mob hauv cov neeg mob uas muaj CKD theem 2-4, peb tau ua qhov kev soj ntsuam yav tom ntej nyob rau hauv Chronic Renal Insufficiency Cohort (CRIC). Peb tau xav tias qhov siab DCA qib yuav cuam tshuam nrog kev pheej hmoo siab dua ntawm atherosclerotic CVD, lub plawv tsis ua haujlwm, kab mob raum kawg (ESKD), thiab tag nrho-ua rau kev tuag ntawm 3,147 CRIC cov neeg koom nrog.
Txoj Kev Kawm CRIC
Txoj kev tshawb fawb CRIC yog ib qho kev soj ntsuam ntau ntawm cov neeg mob nrogCKD theem 2-4.15,16 The main objective is to investigate risk factors for the development of CVD, progression to ESKD, and mortality in the CKD population. In phase 1 of the CRIC study, 3,939 patients were enrolled across 7 sites from 2003 to 2008. Exclusion criteria included the inability to consent, institutionalization, enrollment in other studies, pregnancy, New York Heart Association class 3-4 heart failure, human immunodeficiency virus infection, cirrhosis, myeloma, polycystic kidney disease, renal cancer, recent chemotherapy or immunosuppressive therapy, organ transplantation, or prior treatment with dialysis for >1 hli. Txhua tus neeg tuaj koom tau txais kev pom zoo, thiab cov txheej txheem tau txais kev pom zoo los ntawm txhua qhov chaw kawm lub koom haum saib xyuas lub koom haum (University of Pennsylvania IRB raws tu qauv 807882). Cov ntaub ntawv hauv qab no tsis tuaj yeem muab qhia tawm rau pej xeem los tiv thaiv kev ceev ntiag tug ntawm cov tib neeg uas koom nrog hauv txoj kev tshawb no
PLAIN-LANGUAGE SUMMARY
Ua kom cov ntshav qab zib ntau ntaudeoxycholic acid(DCA), cov kua tsib theem nrab, tau cuam tshuam nrog vascular calcification hauv cov neeg mob uas muaj kab mob raum ntev (CKD). Siv cov ntaub ntawv los ntawm Kev Tshawb Fawb Txog Lub Raum Tsis Txaus Siab, peb tau sim cov kev sib koom ua ke ntawm cov qib DCA siab thiab nce kev pheej hmoo ntawm cov kab mob plawv, CKD kev loj hlob, thiab kev tuag ntawm cov neeg mob CKD. DCA tau cuam tshuam nrog cov txiaj ntsig kev kho mob hauv qhov kev faib tawm uas tsis yog kab. Siv Cox regression, peb pom tias DCA qib siab tshaj qhov nruab nrab ntawm nws tus kheej cuam tshuam nrog kev pheej hmoo siab dua ntawm cov kab mob raum kawg thiab kev tuag tab sis tsis yog nrog cov xwm txheej atherosclerotic thiab lub plawv tsis ua haujlwm. DCA qib qis dua qhov nruab nrab tsis cuam tshuam nrog cov txiaj ntsig kho mob. Kev tshawb fawb ntxiv yog xav tau los tshawb xyuas DCA ntxiv hauv CKD.
Kawm Tsim
Peb tau ua txoj kev tshawb fawb txog kev soj ntsuam yav tom ntej ntawm 3,147 tus neeg koom nrog CRIC txoj kev tshawb fawb, uas peb ntsuas kev yoo mov DCA qib hauv cov khoom kuaj ntshav uas tau sau tseg ntawm 1- xyoo rov qab mus ntsib, uas yog lub hauv paus mus ntsib peb txoj kev kawm. Peb tsis suav nrog 419 tus neeg tuaj koom los ntawm lub hauv paus rau xyoo 1 mus ntsib leej twg tuag, tau ploj mus rau kev soj ntsuam, tshem tawm ntawm txoj kev kawm, lossis tsis tuaj kawm xyoo 1. Los ntawm 3,520 tus neeg koom nrog uas tuaj koom xyoo 1 mus ntsib, peb tsis suav nrog 373 tus neeg koom uas tsis muaj cov qauv khaws cia, uas tsis yoo mov thaum lub sijhawm ntshav, lossis cov uas tau nce mus rau ESKD (Fig S1). Vim tias peb tau soj ntsuam cov xwm txheej tom qab xyoo 1 atherosclerotic thiab lub plawv tsis ua haujlwm, cov neeg koom nrog cov xwm txheej no ua ntej 1- xyoo rov qab mus ntsib tau khaws cia hauv txoj kev tshawb no.
Nphav
Qhov tshwm sim thawj zaug yog ceev DCA qib ntawm CRIC txoj kev kawm 1- xyoo rov qab mus ntsib. Cov qauv yoo mov tau siv los tswj rau kev nce qib tom qab ntawm DCA theem.17 Cov qauv khaws cia khov khov tau raug xa mus rau cov dej khov qhuav los ntawm CRIC Study Central Laboratory ntawm University of Pennsylvania mus rau chav kuaj Dr Miyazaki ntawm University of Colorado. DCA qib tau ntsuas siv cov kua chromatography-tandem huab hwm coj spectrometry, raws li yav dhau los tau piav qhia.18,19 Luv luv, 100 μL ntawm tib neeg cov ntshav tau diluted nrog 300 μL ntawm acetonitrile txias uas muaj 30 ng ntawm D6-DCA (Cambridge Isotope Laboratory) raws li tus qauv sab hauv. Cov tshuaj tau dhau los ntawm Phree phospholipid tshem tawm phaj (Phenomenex), thiab cov kuab tshuaj tau evaporated nrog cov pa roj nitrogen. Tom qab ntawd cov kua dej tau rov ua dua tshiab hauv 100 μL ntawm 10-mM ammonium acetate tsis muaj. Cov qauv no tau txheeb xyuas nrog Applied Biosystems 3200 qTRAP kua chromatography-tandem mass spectrometry.14 Qhov sib txawv ntawm qhov sib txawv ntawm qhov kev ntsuas DCA yog 4.3%. Kaum tsib feem pua ntawm cov qauv (472 ntawm 3,147) tau qis dua qhov kev kuaj pom, txhais los ntawm lub chaw kuaj mob raws li<4 ng/mL. These undetectable results were replaced with the value of 2 ng/ mL, half of the lower limit of detection.20,21
Cov txiaj ntsig
Cov txiaj ntsig tau hloov pauv tau tshawb xyuas yog lub sijhawm los ntawm 1- xyoo rov qab mus saib xyuas cov xwm txheej atherosclerotic thiab lub plawv tsis ua haujlwm, ESKD, thiab tag nrho cov neeg tuag. Cov xwm txheej Atherosclerotic thiab lub plawv tsis ua haujlwm uas tshwm sim ua ntej 1- xyoo rov qab mus ntsib tsis tau suav tias yog cov xwm txheej, thiab cov neeg mob cuam tshuam tau khaws cia hauv txoj kev tshawb fawb los ntsuas cov txiaj ntsig tom qab xyoo 1. Cov xwm txheej Atherosclerotic thiab lub plawv tsis ua haujlwm tau txheeb xyuas txhua 6 lub hlis thiab txiav txim siab los ntawm kev tshuaj xyuas cov ntaub ntawv kho mob raws li qhov ua tau, qhov tshwm sim, lossis cov xwm txheej tseeb. Adju-dicated atherosclerotic cov xwm txheej tau txhais tau tias ua tau, qhov tshwm sim, lossis qhov tseeb myocardial infarction, qhov tshwm sim los yog qhov tseeb, lossis kab mob peripheral arterial. Kev txiav txim siab txog lub plawv tsis ua haujlwm tau txhais tias yog kev nkag mus rau hauv tsev kho mob rau cov tsos mob thiab cov tsos mob ntawm lub plawv tsis zoo, thiab peb qhov kev tshuaj xyuas suav nrog ob qho xwm txheej tshwm sim thiab qhov tseeb txiav txim siab lub plawv tsis ua haujlwm. Kev nce qib mus rau ESKD tau txheeb xyuas txhua 6 lub hlis, lees paub los ntawm kev tshuaj xyuas cov ntaub ntawv kho mob, thiab ntxiv nrog cov ntaub ntawv los ntawm Tebchaws Meskas Lub Raum Cov Ntaub Ntawv. Cov neeg tuag tau lees paub los ntawm daim ntawv pov thawj tuag.22 Cov neeg koom nrog tau ua raws li kev tuag, kev ploj mus tom qab, lossis kev tswj hwm qhov kawg ntawm kev rov qab los rau lub Cuaj Hlis 2015, nrog lub sijhawm ua raws siab tshaj 11.2 xyoo. Tag nrho cov xwm txheej kho mob uas txaus siab ua ntej qhov kawg ntawm kev soj ntsuam tau raug kaw.
Covariates
Covariates suav nrog cov pej xeem, cov xwm txheej ntawm cov hlab plawv, kev siv tshuaj, thiab cov nqi kuaj mob uas niaj hnub sau los ntawm CRIC txoj kev tshawb fawb. Cov ntaub ntawv hais txog pej xeem, keeb kwm kev kho mob, thiab tshuaj tau tshaj tawm tus kheej thiab tau txais ntawm 1- xyoo rov qab mus ntsib. Kev kuaj ntshav thiab tso zis tau ntsuas hauv nruab nrab ntawm cov qauv ntsuas.15,16 Cov ntaub ntawv ntxiv ntawm covariates tau nthuav tawm hauv Yam S1.
Kev txheeb cais
Lub hauv paus (xyoo 1) cov yam ntxwv ntawm CRIC cov neeg tuaj koom tau nthuav tawm raws li tag nrho cov pej xeem thiab los ntawm DCA quartiles (Table 1, Table S1). Nquag faib cov hloov pauv tsis tu ncua tau nthuav tawm raws li qhov nruab nrab ± tus qauv sib txawv (SD), qhov sib txawv tsis tu ncua tau nthuav tawm raws li qhov nruab nrab nrog qhov sib txawv. Cate gorical variables yog nthuav tawm raws li proportions. Kev ntsuas qhov sib txawv ntawm cov quartiles tau sim siv kev tshuaj xyuas qhov sib txawv rau qhov sib txawv tsis tu ncua nrog cov kev faib tawm ib txwm, Wilcoxon-Mann-Whitney kev ntsuam xyuas rau qhov sib txawv tsis tu ncua nrog skewed distributions, thiab χ2 kev ntsuam xyuas rau categorical variables. DCA tau hloov pauv hauv txhua qhov kev tshuaj ntsuam vim nws qhov kev faib tawm tsis zoo. Covariates ploj lawm<1.5%. If variables were missing at the year 1 visit, we used data from the initial study visit. We used Tobit regression, which is designed to handle left-censored data, to identify the independent predictors of DCA levels.23 We used Wald χ2 values and P values from the type III analysis of effects to determine the strength of association between log-DCA and the independent variables. In Table S2, we used Pearson correlations to determine the associations between dietary data and DCA.
Peb pom tias cov koom haum ntawm DCA nrog cov txiaj ntsig sib txawv yog qhov tsis sib xws. Txhawm rau ua kom yooj yim rau kev ua qauv ntawm kev sib koom ua ke ntawm DCA thiab cov txiaj ntsig, peb siv Cox proportional hazards model siv penalized cubic splines nrog 1 knot.24 Peb tau txiav txim siab qhov zoo tshaj plaws ntawm cov degrees ntawm kev ywj pheej thiab qhov chaw ntawm lub pob caus hauv cubic splines los ntawm kev sib piv cov qauv nrog sib txawv. qib kev ywj pheej thiab xaiv tus qauv nrog yam tsawg kawg nkaus Akaike's Information Criteria thiab Bayesian Information Criteria.25,26 Lub pob caus yog nyob ntawm qhov nruab nrab ntawm DCA tus nqi 68.45 ng / mL thiab tau txhais raws li tus nqi siv (kev phom sij piv [HR] {{6 }} 0).
Plaub tus qauv raug hloov kho raws li cov qauv hauv qab no. Qauv 1 tau hloov kho rau qhov chaw kawm, hnub nyoog, poj niam txiv neej, haiv neeg, thiab haiv neeg Hispanic. Qauv 2 tau hloov kho rau covariates hauv qauv 1, ntxiv rau lub raum thiab cov hlab plawv (kwv yees glomerular filtration rate, log-transformed urinary protein, diabetes, systolic blood pressure, tus naj npawb ntawm cov tshuaj antihypertensive, haus luam yeeb tam sim no, keeb kwm ntawm CVD, tag nrho cov roj cholesterol. , thiab siv statin). Qauv 3 tau hloov kho rau yam hauv qauv 2, ntxiv rau cov log-transformed interleukin-6 thiab log-transformed C-reactive protein. Qauv 4 tau hloov kho rau cov yam ntxwv hauv cov qauv 3, ntxiv rau cov log-transformed fibroblast kev loj hlob yam khoom - 23, log-transformed parathyroid hormone, phosphate, calcium, thiab albumin. Hauv Table S3, qauv 5 hloov kho rau yam hauv qauv 4, ntxiv rau hnub nyoog ntawm tus qauv DCA.
Hauv Table 2, peb tshaj tawm HRs thiab 95% kev ntseeg siab ncua sij hawm (CIs) ib 1 SD ntawm log-transformed DCA piv nrog HR ntawm qhov nruab nrab DCA tus nqi (68.45 ng / mL). Daim duab 1 nthuav qhia HRs nrog 95% CIs los ntawm tus qauv 4 rau txhua qhov tshwm sim. Ib feem ntawm qhov nkhaus saum toj ntawm y-scale siv kab ntawm 1.0 tau suav tias yog qhov tseem ceeb. Cov DCA qhov tseem ceeb ntawm x-axis tau rov qab hloov los ntawm SD ntawm log-transformed DCA qhov tseem ceeb rau lawv qhov ntsuas qub hauv chav tsev ntawm DCA (ng / mL). Cov ntaub pua plag hauv qab ntawm daim duab 1 qhia txog cov kev ntsuas.27
Peb suav Schoenfeld residuals hauv cov qauv hloov kho tag nrho ntawm cov neeg uas muaj DCA qhov tseem ceeb hauv qab qhov nruab nrab thiab siab dua qhov nruab nrab. Peb tau txheeb xyuas tias tsis muaj kev ua txhaum cai ntawm qhov kev xav ntawm kev phom sij rau DCA hauv tag nrho cov qauv kev tshwm sim. Txhua qhov kev txheeb xyuas tau ua tiav siv Survival, SmoothHR, thiab Splines pob hauv R, version 3.4.4, thiab SAS version 9.4. Ob sab P qhov tseem ceeb < 0.05 tau suav tias yog qhov tseem ceeb.
Supportive Service Ntawm Wecistanche-Qhov loj tshaj plaws cistanche exporter nyob rau hauv Tuam Tshoj:
Email: wallence.suen@wecistanche.com
Whatsapp / Tel: +86 15292862950
`https://www.xjcistanche.com/cistanche-shop
