Ntu Ⅰ Kev Koom Tes Ntawm Indoxyl Sulfate Thiab Dialysis Initiation Thiab Cardiac Outcomes in Chronic Kidney Disease Patients
May 16, 2023
Abstract
Indoxyl sulfate, protein-bound uremic toxin, tau tshaj tawm tias yog atherosclerosis thiab fibrosis accelerator. Txoj kev tshawb no tsom los txiav txim siab seb cov ntshav qab zib indoxyl sulfate puas cuam tshuam nrog kev mob plawv, kab mob plawv, thiab lub raum mus rau kev lim ntshav hauv cov neeg mob uas muaj kab mob raum (CKD).
Txoj kev tshawb fawb yav tom ntej tau tso npe rau 89 tus neeg mob nrog CKD theem 3 txog 5 tus neeg mob. Cov ntaub ntawv tshawb fawb biochemistry thiab indoxyl sulfate tau ntsuas. Txhua tus neeg mob tau kuaj echocardiographic. Ntiaj teb longitudinal strain (GLS) tau suav nrog siv ob-dimensional speckle nrhiav. Cov txiaj ntsig kev kho mob suav nrog cov xwm txheej hauv plawv thiab kev pib lim ntshav tau sau tseg thaum lub sijhawm 2- xyoo rov qab.
Patients were divided into 2 groups based on the median value of serum indoxyl sulfate (low and high indoxyl sulfate groups). Kaplan–Meier analysis revealed that patients with higher indoxyl sulfate (≥6.124 mg/L) were significantly associated with renal progression to dialysis (p < 0.001). There was no significant difference in cardiovascular events between the 2 groups (p = 0.082). In addition, serum indoxyl sulfate level was independently associated with GLS (r = 0.62; p = 0.01). The risk of cardiovascular events was significantly higher in patients with impaired GLS (>−16 feem pua ) (p=0.015).
Ntshav qab zib indoxyl sulfate qib yog ib qho kev kwv yees tseem ceeb rau CKD kev nce mus rau kev lim ntshav thiab tau cuam tshuam nrog GLS, ib qho speckle-tracking echocardiography parameter uas sawv cev rau thaum ntxov LV systolic dysfunction. Tsis tas li ntawd, GLS tau cuam tshuam nrog cov kab mob plawv hauv cov neeg mob CKD. Kev ntsuas ntshav hauv indoxyl sulfate tuaj yeem pab txheeb xyuas qhov kev lim ntshav siab thiab mob plawv CKD cov neeg mob tshaj li cov xwm txheej pheej hmoo.
Ntsiab lus
indoxyl sulfate, mob raum kab mob, echocardiographic tsis, lub raum tshwm sim, kab mob plawv.
Nyem qhov no kom tau txaisCov txiaj ntsig Cistanche
Taw qhia
Mob raum mob (CKD) yog ib qho tseem ceeb tshaj plaws hauv ntiaj teb cov teeb meem kev noj qab haus huv thiab ua rau muaj kab mob plawv (CVD). Hauv cov neeg mob CKD, qhov feem ntau ntawm lub plawv tsis ua haujlwm thiab mob myocardial infarction yog kwv yees li plaub npaug ntau dua li cov neeg ib txwm muaj. Tsis tas li ntawd, cov xwm txheej ntawm cov hlab plawv thiab cov kev pheej hmoo ntawm kev tuag tau nce ntxiv nrog rau cov qib ntawm lub raum tsis ua haujlwm. Kev loj hlob ntawm cardiomyopathy thiab vasculopathy hauv cov neeg mob CKD tsis tuaj yeem piav qhia tsuas yog los ntawm cov xwm txheej pheej hmoo, xws li kub siab, dyslipidemia, ntshav qab zib, thiab haus luam yeeb. Lwm qhov kev pheej hmoo ntxiv nrog rau kev ntxhov siab oxidative, o, endothelial dysfunction, thiab uremic-specific kev pheej hmoo yam xws li uremic toxin tsub zuj zuj, anemia, thiab pob txha pob txha (CKD-MBD), kuj tau npaj.
Indoxyl sulfate yog ib qho tseem ceeb protein-bound uremic toxin muab los ntawm indole, ib tug by-product ntawm tryptophan metabolism hauv plab microbiome. Indoxyl sulfate tsis tuaj yeem tshem tawm tau zoo hauv cov neeg mob lub raum tsis txaus, ua rau muaj kev cuam tshuam hauv lub cev thiab ua rau muaj kev puas tsuaj rau ntau lub cev. Hauv vitro thiab tsiaj kev tshawb fawb yav dhau los tau qhia txog kev koom tes ntawm indoxyl sulfate thiab lub raum tubular cell puas, tubulointerstitial fibrosis, plawv fibrosis, vascular calcification, thiab atherosclerosis. Cov kev tshawb fawb soj ntsuam tau nce ntxiv qhia tias indoxyl sulfate kuj tseem tuaj yeem ua rau CVD thiab kev tuag hauv cov neeg mob CKD. Txawm li cas los xij, kev sib koom ua ke ntawm cov ntshav qab zib indoxyl sulfate thiab lub raum kev loj hlob tshwj xeeb tshaj yog kev pib lim ntshav nrog rau cov qauv ntawm lub plawv txawv txav hauv cov neeg mob CKD tseem xav tau cov pov thawj ntxiv.
Hauv qhov kev cia siab no 2- xyoo tom qab kev tshawb fawb pawg, peb tsom los txiav txim siab seb qib indoxyl sulfate puas cuam tshuam nrog rau lub raum kev loj hlob thiab kev mob plawv tsis zoo uas sawv cev los ntawm echocardiographic tsis. Tsis tas li ntawd, txoj kev tshawb no kuj tau tshawb xyuas seb indoxyl sulfate thiab echocardiography-txog kev mob plawv tsis zoo yog qhov muaj peev xwm kwv yees ntawm cov hlab plawv (CV) cov xwm txheej hauv pre-dialysis CKD theem 3-5 cov neeg mob.
Qhuav CistanchethiabCistanche ntsiav tshuaj
Cov txheej txheem
1. Kawm cov pej xeem
Peb tau tso npe ua ntej kev lim ntshav CKD theem 3-5 cov neeg mob uas tau mus rau qhov chaw kho mob sab nraud hauv Lub Tsev Kho Mob Nephrology ntawm King Chulalongkorn Memorial Tsev Kho Mob, Bangkok, Thaib teb, txij lub Ib Hlis 2017 txog Lub Kaum Ob Hlis 2020. Cov txheej txheem suav nrog yog cov neeg mob hnub nyoog> 18 xyoo nrog kwv yees. glomerular pom tus nqi (eGFR) < 60 mL / min / 1.73m2txhais los ntawm Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation rau tsawg kawg 3 lub hlis. Cov txheej txheem cais tawm yog cov neeg mob CVD (mob mob hlab ntsha tawg, mob plawv tsis ua haujlwm, kab mob cerebrovascular) hauv 3 lub hlis dhau los.
2. Cov ntaub ntawv khaws cia
Cov ntaub ntawv pej xeem, suav nrog hnub nyoog, poj niam txiv neej, ua rau CKD, thiab keeb kwm kho mob tau txais. Txhua tus neeg mob tau txais kev ntsuas lub hauv paus hauv kev ntsuas, echocardiography, pob taws-brachial index (ABI), thiab kev ntsuas cardio-ankle vascular index (CAVI). Serum indoxyl sulfate yog ntsuas los ntawm high-performance kua chromatography (HPLC) ntawm Pharmacology Department, Kws qhia ntawv ntawm tshuaj, Chulalongkorn University.
Tag nrho cov echocardiographic tsis tau ua thiab ntsuas los ntawm ib tus kws kho plawv uas paub txog qhov muag tsis pom cov ntaub ntawv tus neeg mob. Ob-Dimensional (2D) thiab 2D coj M-hom dluab raug kaw los ntawm cov qauv kev pom (4-chamber, 2-chamber, thiab apical long-axis) siv grey-scale harmonic imaging thiab khaws cia rau hauv raw cov ntaub ntawv hom ntawv (Epiq CVx, Philips Medical System, Bothell, Washington). Cov duab tau txais ntawm tus ncej tus nqi ntawm 50 txog 70 ib ob thiab cov voj voog digital tau txais kev cawmdim rau hauv qhov chaw kho qhov muag rau kev tshuaj xyuas offline (Qlab version 10.2, Philips Healthcare). Kev ntsuas echocardiographic suav nrog sab laug atrial (LA) txoj kab uas hla, LA ntim ntsuas (LAVI), kev xa tawm thaum ntxov sau nthwv dej tshaj tawm (E), lig transmitral filling yoj tshaj tawm (A), thaum ntxov diastolic mitral annular tshaj tawm (e'), E / A thiab E / e' ratios, sab laug ventricular end-diastolic txoj kab uas hla (LVDd), thiab sab laug ventricular end-systolic txoj kab uas hla (LVDs). Sab laug atrial enlargement tau txhais tias LAVI > 34 m2. Sab laug ventricular (LV) huab hwm coj tau suav nrog cov qauv: LV huab hwm coj=0.8 × {1.04[([LV sab hauv qhov ntev ntxiv rau septal phab ntsa thickness ntxiv rau phab ntsa thickness] 3 - LV sab hauv qhov ntev3)] ntxiv rau 0.6 g. Sab laug ventricular mass index (LVMI) yog xam los ntawm kev faib sab laug ventricular mass los ntawm lub cev nto. Left ventricular hypertrophy (LVH) tau txhais tias LVMI> 95 g / m2Hauv cov poj niam thiab> 115 g / m2hauv cov txiv neej. Qhov kawg-diastolic thiab qhov kawg-systolic ntim tau siv los suav cov ventricular ejection feem (LVEF) siv Simpson biplane txoj kev los ntawm apical 4- thiab 2-chamber views. Preserved LVEF tau txhais tias Loj dua lossis sib npaug li 50 feem pua.
LV systolic dysfunction was diagnosed by using global longitudinal strain (GLS) which is a parameter that expresses LV longitudinal shortening as a percentage (change in length as a proportion to baseline length). GLS measurements were performed offline utilizing commercially available dedicated automated software. The endocardial borders were traced in the end-systolic frame of the 2D images from the 3 apical views, assessed tracking quality and integration. Frame-by-frame tissue speckle tracking of the LV endocardium was performed and endocardial borders were readjusted manually until satisfactory tracking was achieved. GLS was calculated as the mean strain of segments which the American Heart Association recommended. GLS varies typically with age, sex, and LV loading condition. Therefore, defining abnormal GLS is not straightforward. Previous studies have demonstrated that healthy individuals have GLS ranging from −16 to −20%. In our study, impaired GLS was defined as >-16 feem pua (tus nqi qis dua qhia txog GLS qhov tsis zoo).
ABI and CAVI were used to determine vascular stiffness at baseline by using a portable ultrasonography-based machine (VaSera VS-200; Fukuda-Denshi Company, Tokyo, Japan). ABI is determined by the highest systolic pressure on the foot of that side/ average of the highest pressure from both arms, while the CAVI score was calculated by the machine. The ABI scores < 0.9 and 0.91–0.99 are peripheral arterial disease and borderline, respectively, while ABI at 1–1.4 and >1.4 yog ib txwm thiab tsis-compressible hlab ntsha, feem. Qhov qhab nia CAVI < 8 thiab 8–9 yog qhov qub thiab muaj kev pheej hmoo rau atherosclerosis, feem, thaum CAVI> 9 tuaj yeem ua rau atherosclerosis.
Cistanche ntxiv
3. Kev Tshawb Fawb Kev Tshawb Fawb
Cov neeg koom nrog tau ua raws li txhua 3 lub hlis rau 24 lub hlis. Ua tiav kev soj ntsuam kuaj mob thiab ntsuas lub raum ua haujlwm tau raug kaw. Cov neeg mob tau txais kev saib xyuas CKD los ntawm ib pab neeg ua haujlwm ntau yam xws li nephrologists, nephrology kws tu neeg mob, thiab cov kws kho mob raum. Concomitant pharmacological thiab non-pharmacological kev kho mob xws li renin-angiotensin-aldosterone system (RAAS) inhibitors, anemia thiab CKD-MBD tswj, thiab ntshav siab tswj tau raug sau tseg raws li kev kho mob lub hom phiaj ntawm cov txheej txheem txheem. Cov lus qhia noj zaub mov tau tsim los ntawm cov kws noj zaub mov thiab nephrologists thoob plaws lub sijhawm kawm.
4. Kev txhais cov txiaj ntsig
Thawj qhov tshwm sim yog CKD kev loj hlob, txhais tau tias yog qhov pib ntawm kev kho lub raum hloov (pib ntawm kev saib xyuas kev lim ntshav lossis hloov lub raum). Qhov pib ntawm kev lim ntshav tau ua raws li cov ntaub ntawv kuaj mob, kev noj zaub mov zoo, thiab cov tsos mob ntawm uremic los ntawm tus kws kho mob nephrologist hauv kev sab laj lossis tus neeg mob sab nraud. Cov txiaj ntsig thib ob yog cov xwm txheej ntawm cov hlab plawv (CV) txhais tau tias ua rau tuag taus lossis tsis tuag myocardial infarction (MI), angina pectoris, congestive plawv tsis ua haujlwm, tuag sai sai, cerebrovascular tsis meej, lossis kab mob peripheral arterial.
5. Kev txheeb xyuas qhov tseeb
Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias ± (tus qauv sib txawv; SD) rau ib txwm faib lossis nruab nrab (interquartile ntau yam; IQR) rau cov khoom sib txawv tsis tu ncua. Categorical cov ntaub ntawv tau piav raws li tus lej thiab feem pua. Kev txheeb xyuas qhov tseem ceeb ntawm cov pab pawg ntawm cov hauv paus ntsiab lus tau soj ntsuam los ntawm One-way ANOVA lossis Kruskal-Wallis test. Rau kev tsom xam, cov neeg mob tau muab faib raws li qhov nruab nrab cov ntshav qab zib indoxyl sulfate rau hauv 2 pawg (tsawg thiab siab indoxyl sulfate pawg). Kev sib piv ntawm cov pab pawg qis thiab siab indoxyl sulfate tau soj ntsuam los ntawm chi-square, unpaired t-tests, thiab Mann-Whitney U-test raws li qhov tsim nyog.
Kev sib raug zoo ntawm cov qib indoxyl sulfate thiab qhov sib txawv ntawm kev txaus siab thiab echocardiographic tsis tau raug soj ntsuam siv univariate thiab multivariate linear regression tsom xam rau qhov sib txawv tsis tu ncua. Cov qauv multivariate suav nrog tag nrho cov khoom muaj nqis uas muaj kev sib raug zoo nrog indoxyl sulfate hauv kev tshuaj ntsuam univariate.
Kev kwv yees ntawm cov kab mob plawv tsis muaj sia nyob tau suav los ntawm kev siv Kaplan-Meier txoj kev. Qhov kev xeem Log-rank tau siv los sib piv cov ciaj sia taus nkhaus. Cox proportional hazards regression analysis tau ua los xam qhov phom sij piv (HR) thiab 95 feem pua ntawm kev ntseeg siab (95 feem pua CI) rau cov xwm txheej hauv plawv. Multivariate Cox proportional hazard regression analyzes tau ua los kho ntau yam. Ib tug ob-tailed p-tus nqi < 0.05 tau suav hais tias tseem ceeb. Cov neeg koom nrog cov ntaub ntawv ploj lawm raug cais tawm ntawm kev tshuaj ntsuam. Cov ntaub ntawv tau txheeb xyuas siv Stata Statistical Software version 15.0 (StataCorp LLC, College Station, TX).
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Kullaya Takkavatakarn 1, Jeerath Phannajit 1, Suwasin Udomkarnjananun 1, Suri Tangchitthavorngul 1, Pajaree Chariyavilaskul 2,3, Patita Sitticharoenchai 4, Kearkiat Praditpornsilpa 1, Somchai Eiam-Ong 15, Pawegena
1 Division of Nephrology, Department of Medicine, Kws Qhia Ntawv ntawm Tshuaj, King Chulalongkorn Memorial Tsev Kho Mob, Chulalongkorn University, Bangkok, Thaib teb;
2 Clinical Pharmacokinetics thiab Pharmacogenomics Research Unit, Kws Qhia Ntawv ntawm Tshuaj, Chulalongkorn University, Bangkok, Thaib teb;
3 Department of Pharmacology, Kws Qhia Ntawv ntawm Tshuaj, Chulalongkorn University, Bangkok, Thaib teb;
4 Division of Cardiology, Department of Medicine, Kws Qhia Ntawv ntawm Tshuaj, King Chulalongkorn Memorial Tsev Kho Mob, Chulalongkorn University, Bangkok, Thaib teb;
5 Lub Chaw Tshawb Fawb Txog Kab Mob Metabolic hauv Cov Neeg Mob CKD, Kws Qhia Tshuaj, Chulalongkorn University, Bangkok, Thaib