Cov ntaub ntawv pov thawj ntawm mob raum mob rau cov neeg mob uas tsis tau raws li KDIGO Cov Cai Rau Cov Kab Mob Raum Ntev

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Cov ntsiab lus tsis ua raws li KDIGO cov txheej txheem raumob raumkab mob (CKD), ienormoalbuminuric (urinary albumin: creatinine ratio, UACR<30 mg/g）="" individuals="" with="" an="" estimated="" glomerular="" filtration="" rate="">60 mL / min / 1.73 m², raug suav hais tias tsis muaj kev pheej hmoo siab plawv lossis lub raum cuam tshuam nrog cov kab mob raum, tab sis qhov tshwm sim ntawmsubclinical atherosclerosis, kab mob plawv, thiabCKD kev nce qibtwb tau nce nyob rau hauv qhov siab-ib txwm UACR ntau (10-30 mg/g). Kev cuam tshuam ua ntej hauv qhov subclinical pre-CKD theem yuav txo qis kev pheej hmoo ntawm cardiorenal. Txawm li cas los xij, cov cuab yeej los kwv yees kev txhim kho albuminuria thiab txheeb xyuas cov ncauj lus uas yuav tau txais txiaj ntsig zoo tshaj plaws los ntawm kev cuam tshuam yog txwv. Cov ntaub ntawv tsis ntev los no tau txheeb xyuas cov kev hloov pauv ntawm cov zis molecular nyob rau hauv normoalbuminuria mob, muaj xws li hloov pauv urinary peptidome, proteome, thiab metabolome, uas sawv cev rau subclinical organ puas thiab cov txheej txheem xws li o, thiab oxidative kev nyuaj siab, tricarboxylic acids voj voog deregulation, impaired fatty acids - oxidation. tubular reabsorption puas lawm.

Keywords: albuminuria, cardiorenal risk, kab mob plawv, mob raum,oxidation ntawm fatty acids, metabolomics, proteomics, tubular reabsorption

Cov kab mob raum mob ntev (CKD) tau npaj los ua lub ntiaj teb thib tsib ua rau tuag los ntawm 2040 vim tsis muaj kev xav tau hauv kev kuaj mob ntxov thiab kho tus mob [1]. Uri-nary albumin: creatinine ratio (UACR) nyob rau hauv qhov nruab nrab nce ntau (piv txwv li 30-300 mg/g) yog ib qho qhia txog kev puas tsuaj rau hauv nruab nrog cev thiab ib qho kev pheej hmoo ntawm kev mob plawv thiab mob raum mus rau txhua theem. ntawm lub raum ua haujlwm raws li kev ntsuas los ntawm qhov kwv yees glomerular filtration rate (eGFR).UACR 30 mg / g yog qhov txiav tawm tam sim no rau kev kuaj mob ntawm CKD. CKD kuj tuaj yeem kuaj tau raws li eGFR<60 ml/min/1.73="" m².="" equations="" for="" renal="" risk="" prediction="" have="" been="" developed="" recently,="" aiming="" for="" the="" earlier="" identification="" of="" patients="" at="" increased="" risk="" of="" ckd="" progression.="" in="" this="" line,="" high="" albuminuria="" was="" associated="" with="" the="" predicted="" 5-year="" absolute="" risk="" of="" ckd="" defined="" by=""><60 ml/min/1.73="" m²,="" regardless="" of="" the="" presence="" of="" diabetes="" [2].="" subjects="" not="" meeting="" kdigo="" criteria="" for="" ckd="" (normoalbuminuric="" subjects="" with="" egfr="">60 mL / min / 1.73 m²) feem ntau suav hais tias tsis muaj kev pheej hmoo siab plawv lossis lub raum muaj feem cuam tshuam rau cov kab mob raum, tab sis cov ntaub ntawv pov thawj pom tseeb txhawb kev sib koom ua ke ntawm albuminuria thiab cardiorenal pheej hmoo pib nrog UACR qib qis dua 30 mg / g. Qhov tshwm sim ntawm subclinical atherosclerosis [3,4], cov xwm txheej ntawm cov hlab plawv [5], thiab lub plawv tsis ua haujlwm [6] tau nce ntxiv hauv cov kab mob siab li qub.normoalbuminuria (UACR =10-30 mg/g).

Nyem qhov no kom paub ntau ntxiv txog Cistanche

Daim duab 1: Txoj hauv kev tseem ceeb ntawm cov kab mob lom neeg thiab cov kev hloov pauv molecular tau pom nyob rau hauv normoalbuminuric hypertensive kev kawm nrog UACR nyob rau hauv qhov siab-ib txwm ({2}} mg / g) txawm tias RAS thaiv, piv nrog UACR<10 mg/g="" [8,="" 11,="">

Hauv qhov xwm txheej no, kev cuam tshuam ua ntej kom qeeb qeeb ntawm albuminuria kev loj hlob thiab txo qis kev pheej hmoo ntawm cov hlab plawv yuav xav tau nyob rau theem subclinical ntawm normoalbuminuria nrog rau lub raum ua haujlwm. Txawm li cas los xij, biomarkers yuav tsum tau txheeb xyuas cov neeg mob uas muaj kev pheej hmoo siab dua nyob rau hauv cov pej xeem no rau kev xa mus los ntawm kev saib xyuas thawj zaug rau kev pheej hmoo plawv lossis cov chaw kho mob nephrology. Hauv qhov kev nkag siab no, muaj qhov sib txawv loj ntawm cov pov thawj thiab tsim kev cuam tshuam kev kho mob, uas tuaj yeem txhim kho cov txiaj ntsig hauv cov pej xeem dav. Yog li, cov kev kawm tsis tau raws li KDIGO cov qauv rau CKD feem ntau yog sab nraud ntawm qhov kev cuam tshuam rau kev kho mob yog tias tsis muaj lwm yam kev pheej hmoo tshwm sim, tab sis tseem tuaj yeem tsim cov kab mob plawv thiab lub raum tsis ua haujlwm hauv lub sijhawm nruab nrab. Qhov no yog ib feem ntawm qhov tshwm sim ntawm cov cuab yeej txwv muaj uas yuav cia siab (xav tau) kev nce qib albuminuria.

Kev cuam tshuam cov tshuaj pharmacological yav dhau los nrog raum thiab cov tshuaj cardioprotective yuav ua rau muaj kev ncaj ncees nyob rau hauv cov ntsiab lus nyob rau theem pib ntawm kev pheej hmoo cardiorenal yog tias cov kev sim tshuaj ntsuam pom tau zoo dua. Txawm li cas los xij, kev ua tiav ntawm cov kev sim tshuaj no yuav nyob ntawm qhov kev txhawb nqa ntawm cov neeg koom nrog kev pheej hmoo siab dua thiab kev nkag siab zoo dua ntawm cov xwm txheej molecular uas piav qhia vim li cas albuminuria kev nce qib sib txawv ntawm cov kev kawm categorized hauv tib pab pawg kho mob raws li hauv paus hauv UACR, ntshav qab zib, ntshav siab lossis eGFR.

Qhov muaj nyob ntawm cov lus nug uas tsis tau daws teeb meem no tuaj yeem ua rau muaj kev nkag siab tsis txaus ntawm cov xwm txheej molecular

cuam ​​tshuam nrog kev txhim kho albuminuria. Nyob rau hauv cov xwm txheej nyuaj no, tus cwj pwm ntawm cov xwm txheej molecular tuaj yeem pab ua kom muaj kev pheej hmoo ntawm kev mob plawv thaum ntxov thiab hauv kev txiav txim siab cov txheej txheem molecular uas ua rau kev nce qib albuminuria. Thaum cov kev tshawb fawb molecular hauv cov ntsiab lus normoalbuminuric nrog rau lub raum kev ua haujlwm tsis txaus, cov txheej txheem biology tsis ntev los no tau tso qee lub teeb hauv thaj chaw no.

In hypertensive subjects with normoalbuminuria under chronic renin-angiotensin system (RAS)blockade,>2500 urinary proteins tau txheeb xyuas los ntawm qhov tsis pom kev loj spectrometry. Cov qauv ntawm cov zis sib txawv hauv cov neeg mob uas muaj normoalbuminuria nyob rau hauv qhov siab-ib txwm (UACR 10-30} mg / g) los ntawm cov neeg uas muaj UACR<10 mg/g="" [7].="" alpha-1="" antitrypsin(a1at),="" kininogen-1="" (kng1),="" and="" vitamin="" d-binding="" protein="" (vtdb)="" were="" differentially="" present="" in="" urine="" and="" also="" differentially="" expressed="" in="" human="" kidneys="" and="" aorta="" samples,="" suggesting="" that="" early="" renal="" and="" vascular="" damage="" may="" be="" molecularly="" reflected="" in="" the="" urine="" of="" patients="" with="" normoalbuminuria.="" the="" unparalleled="" value="" of="" proteomics="" was="" also="" evidenced="" by="" the="" characterization="" and="" clinical="" development="" of="" ckd273,="" a="" ckd="" risk="" score="" based="" on="" the="" measurement="" of="" 273="" urinary="" peptides="" that="" independently="" predicted="" future="" development="" of="" microalbuminuria="" in="" type="" 2="" diabetic="" patients="" with="" normoalbuminuria="" as="" well="" as="" loss="" of="" gfr="" in="" patients="" with="" normoalbuminuria="" and="" egfr="" above="" 60="" ml/min/1.73="" m²,i.e.="" in="" patients="" not="" fulfilling="" current="" criteria="" to="" diagnose="" ckd="">

Cov zis concentration ntawm metabolites 3-ureidopropionate, oxaloacetate, thiab guanidinoacetate poob qis, thaum malate nce hauv cov neeg mob nrog microalbuminuria: thiab hauv cov neeg mob uas muaj normoalbuminuria nyob rau hauv qhov siab-ib txwm albuminuria ntau piv nrog cov neeg uas muaj qis albuminuria (UACR).<10 mg/g)[10].="" nine="" metabolites="" previously="" associated="" with="" cardiorenal="" risk="" were="" also="" altered="" in="" the="" high-normal="" albuminuria="" range:="" 2-hydroxyphenyl="" acetic="" acid,="" glutamic="" acid,="" n-acetylneuraminic="" acid,="" pipecolic="" acid,="" pyruvic="" acid,="" and="" scylloinositol="" increased,="" and="" α-ketoglutaric="" acid,="" y-aminobutyric="" acid,="" and="" n-phenylalanine="" decreased="" [11].="" the="" presence="" of="" these="" metabolites="" in="" the="" urine="" together="" with="" increased="" levels="" of="" fatty="" acids="" and="" fatty="" acid-binding="" protein-1="" (fabp1),="" and="" alterations="" in="" clathrin-mediated="" endocytosis="" signaling,="" is="" consistent="" with="" defective="" tubular="" reabsorption="" and="" tubular="" damage="" caused="" by="" fatty="" acid="" overload,="" impaired="" mitochondrial="" β-oxidation,="" peroxisome="" proliferator-activated="" receptor="" (ppar)activation="" or="" tricarboxylic="" acid="" cycle="" dysregulation="" (figure="" 1).="" these="" findings="" fit="" well="" with="" evidence="" that="" proximal="" tubular="" injury="" induced="" by="" glucose="" overload,="" albumin,="" and="" its="" ligands,="" or="" other="" stressors,="" leads="" to="" ckd="" progression[12,13].="" in="" proteinuric="" conditions,="" albumin-bound="" fatty="" acids="" may="" contribute="" to="" proximal="" tubule="" fatty="" acid="" overload,="" favoring="" lipotoxicity,="" oxidative="" stress,="" and="" impaired="" proximal="" tubule="" function="" [14].="" in="" this="" line,="" increased="" urinary="" fatty="" acids="" were="" strongly="" correlated="" with="" tubulointerstitial="" injury="" and="" proteinuria="">

Albuminuria yog ob qho tib si ib qho cim ntawm glomerular tsis ua haujlwm thiab ua rau muaj kev raug mob ntawm cov tubular ze ze [16]. Txawm li cas los xij, cov cim kev raug mob tshwj xeeb (mob raum raug mob molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), (FABP), thiab N-acetyl- -D-glucosaminidase ( NAG)) tsis tau ntxiv rau qhov kev pheej hmoo stratification rau CKD kev nce qib ntawm cov ntaub ntawv muab los ntawm UACR thiab eGFR hauv cov neeg mob laus nrog eGFR 20-70 mL/min/1.73 m2² thiab UACR 53.0 mg/g 【 interquartile range (IQR)5.6-503.1] [17]. Qhov no yuav qhia tias UACR nws tus kheej twb tau muab cov ntaub ntawv hais txog tubular kev raug mob ntawm tes pab txhawb rau CKD kev loj hlob uas tsis tau txhim kho ntxiv los ntawm kev ntsuam xyuas lwm yam biomarkers ntawm tubular raug mob.Txawm li cas los xij, hauv cov menyuam yaus uas muaj eGFR 30-90 mL/min/1.73 m² thiab UACR 57.8 mg/g (IQR 8.8-312), zis EGF, KIM-1, monocyte chemoattractant protein-1 (MCP-1) thiab -1 microglobulin tau txuam nrog nrog CKD kev loj hlob tom qab kev hloov pauv ntau yam [18].Qhov no qhia tias cov cim tso zis ntawm tubular cell raug mob yuav ntxiv cov ntaub ntawv rau qhov muab los ntawm albuminuria nyob rau hauv lub qhov rais twv ua ntej (hnub nyoog yau thiab siab dua eGFR).

Hauv kev xaus, nyob rau hauv kev kho mob ntawm normoalbuminuria, ntxiv stratification ntawm kev pheej hmoo tuaj yeem ua tau los ntawm kev siv cov biomarkers tshiab txheeb xyuas los ntawm cov txheej txheem biology. Cov cim no zoo ib yam nrogcev cevkev raug mob, o, hloov lub cev tiv thaiv kab mob, thiab oxidative kev nyuaj siab. Multicentric loj soj ntsuam cohorts yuav tsum validate cov biomarkers, thiab qhov no yuav tsum tau ua raws li los ntawm kev soj ntsuam kev sim uas cuv npe kawm normoalbuminuric cov neeg mob uas khaws cia raum tab sis muaj kev pheej hmoo ntawm cardiorenal kev pheej hmoo raws li tshiab biomarkers thiab randomize lawv mus rau thaum ntxov kev cuam tshuam los yog placebo. Tsuas yog cov ncauj lus kom ntxaws txog kev txhim kho kev kho mob yuav tso cai rau kev txheeb xyuas ntxov thiab kev cuam tshuam tsim nyog los ua kom muaj kev cuam tshuam los ntawm kev nce thoob ntiaj teb lub nra ntawm CKD thiab nws cov txiaj ntsig tsis zoo ntawm cov hlab plawv.