Novel Strategies hauv Nephrology: Yuav Ua Li Cas Los Ntawm Lub Neej Tom Ntej?

TSAB NTAWVMob raum mob(CKD) yuav dhau los ua qhov thib tsib thoob ntiaj teb kev tuag los ntawm 2040. Nws qhov cuam tshuam loj tshaj plaws yog rau kev tuag ntxov ntxov tab sis tus naj npawb ntawm cov neeg mob.raum tsis ua haujlwmxav tau kev kho lub raum hloov (RRT) kuj nce zuj zus. Tam sim no RRT yog qhov zoo tshaj plaws vim qhov tsis txaus ntawm lub raum pub dawb thiab cov txiaj ntsig tsis txaus ntseeg cuam tshuam nrog ob qho tib si hemodialysis thiab peritoneal dialysis. Kev kho mob raum xav tau kev hloov pauv. Hauv qhov kev tshuaj xyuas no, peb muab kev hloov kho tshiab ntawm cov kev paub tshiab thiab thev naus laus zis uas yuav tso cai rau kev kuaj mob ua ntej ntawm CKD, hais txog qhov tam sim no hu ua qhov muag tsis pom kev (xws li kev thaij duab thiab biomarkers), thiab txhim kho cov kev kho rau lub raum (wearable artificial ob lub raum, xenotransplantation, qia. cell-derived therapies, bioengineered thiab bio-artificial ob lub raum).

Ntsiab lus:raum dag, bioengineering,mob raum mob, induced pluripotent qia hlwb, xenotransplantation

Nyem qhov no kom paub CISTANCHE rau CKD kev kho mob

Taw qhia

Tam sim no muaj 850 lab tus tib neeg hauv ntiaj teb nrogmob raum mob(CKD), thiabCKDtau kwv yees los ua qhov thib tsib hauv ntiaj teb ua rau tuag los ntawm 2040 thiab qhov thib ob ua rau tuag hauv cov nroog nrog lub neej ntev los ntawm 2100 [1]. Tsis tas li ntawd, CKD yog qhov ua rau mob ntev nrog qhov tshwm sim ntau ntxiv, muaj ntau, thiab kev cuam tshuam kev noj qab haus huv tag nrho. Lub davhlau ya nyob twg ntawm CKD hu ua kab mob raum kawg (ESRD) lossis lub raum tsis ua haujlwm, yog txhais los ntawm qhov kwv yees glomerular filtration rate (eGFR) qis dua 15 mL / min / 1.73 m2 los ntawm Kab Mob Raum: Txhim Kho Ntiaj Teb Cov txiaj ntsig (KDIGO) , cuam tshuam rau kwv yees li ntawm 800 000 cov neeg mob hauv Tebchaws Meskas (71% ntawm kev lim ntshav thiab 29% nrog raum hloov pauv) [2], nyob rau hauv Tebchaws Europe, kwv yees li ESRD cov pejxeem muaj ntau dua 1 lab tus tib neeg, nrog rau kev hloov pauv ntau thoob plaws ib lub tebchaws. [3, 4] ib.

Kev hloov pauv raum tau ua thawj zaug hauv xyoo 1954 los ntawm Dr Joseph Murray thiab yog tus qauv kub tam sim no rau kev kho mob. Txawm li cas los xij, tseem muaj tsawg dua cov neeg pub dawb tshaj li qhov tsis txaus ntseeg hauv daim ntawv teev npe tos [5]. Mob hemodialysis tau qhia nyob rau xyoo 1960 los ntawm Dr Belding Scribner, thiab txawm hais tias yog hom kev kho mob raum hloov (RRT) tseem cuam tshuam nrog ntau yam teeb meem luv luv thiab ntev. Qhov tseem ceeb, lub neej expectancy ntawm cov neeg mob hauv kev lim ntshav hauv lawv nees nkaum xyoo yog 40 xyoo luv dua ntawm cov pejxeem [6]. Kev lim ntshav peritoneal tsis tshua siv, thiab ntxiv rau cov teeb meem tshwj xeeb (peritonitis, cellulitis, metabolic cuam tshuam) nws raug txwv los ntawm yuav luag inexorable membrane tsis ua hauj lwm [7]. luv dua rau cov pej xeem [6]. Kev lim ntshav peritoneal tsis tshua siv, thiab dhau li cov teeb meem tshwj xeeb (peritonitis, cellulitis, metabolic cuam tshuam) nws raug txwv los ntawm yuav luag tsis muaj peev xwm ua tsis tiav daim nyias nyias [7].

Daim duab 1: Kev saib dav dav ntawm cov tswv yim tshiab hauv nephrology. (Kev kuaj mob yuav muab piav qhia ntxiv hauv daim duab 2.)

Yog li, tag nrho, kev kho mob ntawm ESRD cov neeg mob tseem tsis zoo, vim tias tsis txaus ntawm lub raum pub dawb thiab ntau yam teeb meem cuam tshuam nrog ob qho tib si kev lim ntshav, txawm hais tias muaj ntau yam kev xaiv tau txiav txim siab ntau xyoo. Qee qhov kev txhim kho tsis ntev los no muaj lub peev xwm los hloov kho thaj tsam ntawm nephrology nyob rau xyoo tom ntej. Tsis tas li ntawd, feem ntau ntawm cov neeg mob nrog CKD, tshwj xeeb tshaj yog cov neeg muaj theem 2 thiab theem 3 CKD, yog cov neeg laus uas yuav tsis xav tau ib hom kev kho raum, vim tias cov neeg mob no tuag ntxov ntawm cov kab mob plawv. Yog li, qhov nce tiag tiag ntawm qhov xav tau ntawm RRT yog tsawg dua. Cov txiaj ntsig tseem ceeb ntawm cov tshuaj tshiab xws li sodium-glucose cotransporter 2 (SGLT2) inhibitors thiab mineralocorticoid receptor antagonists (MRAs) yog nyob rau hauv pab pawg neeg mob raum.

Hauv qhov kev tshuaj xyuas no, peb tsom mus piav qhia txog cov kev kuaj mob tshiab hauv nephrology xws li kev nce qib hauv lub raum imag ing thiab cov qauv siv los kwv yees lub raum kev ua haujlwm nrog rau cov kev kho tshiab hauv cov kab mob raum nrog rau cov khoom siv rau lub raum, xenotransplantation, qia cell-derived. Cov kev kho mob, cov qauv bioengineering thiab cov tshuaj tau nce siab (Daim duab 1).

NOVEL DIAGNOSTIC METHODS

Novel diagnostic txoj kev uas yuav tso cai rau kev kuaj mob ua ntej ntawm CKD yog ib qho kev xav tau kev kho mob tsis tau. Kev cia siab rau tam sim no eGFR qhov pib los kuaj CKD txhais tau hais tias los ntawm lub sijhawm CKD kuaj pom, ntau dua 50% ntawm lub raum ua haujlwm tau ploj lawm thiab kev pheej hmoo ua ke ntawm CKD kev loj hlob thiab kev tuag ntxov ntxov tau nce los ntawm ib puag ncig 2- mus rau 7-fold, thaum cov kev cuam tshuam tam sim no txo ​​qhov kev pheej hmoo ntawm qhov tshwm sim tsis zoo los ntawm 20%–40% [8, 9]; Hauv lwm lo lus, kev kuaj mob lig dhau lawm. Thaum CKD tuaj yeem kuaj pom ua ntej raws li qhov muaj txiaj ntsig albuminuria siab, feem ntau cov neeg mob tau nce mus rau CKD qeb G3 thaum muaj lub cev nqaij daim tawv albuminuria, raws li pov thawj los ntawm cov ntaub ntawv kab mob sib kis uas qhia tau tias G3 yog qeb feem ntau ntawm CKD [10], piv txwv li albuminuria tsis pub muaj Kev kuaj mob ua ntej (piv txwv li G1 lossis G2) rau feem ntau cov neeg mob uas tau nce mus rau G3. Qhov no subclinical theem ntawm CKD kev loj hlob, muaj peev xwm kav mus txog kaum xyoo, raws li muaj pov thawj los ntawm cov ntaub ntawv ntawm CKD nyob rau hauv uas peb muaj ib lub cuab tam uas tso cai rau kev kuaj mob ua ntej (xws li sonography rau autosomal dominant polycystic raum kab mob) yog qhov tseeb qhov muag tsis pom kev rau CKD kuaj mob [11 —13]. Muaj ntau txoj hauv kev tab tom kawm los daws qhov tsis pom kev hauv CKD, feem ntau yog siv cov duab kos duab thiab kev ntsuam xyuas ntawm biomarkers hauv cov kua roj lom (Fig. 2).

Kev Ntsuas: ntsuas tus naj npawb nephron raws li kev txiav txim siab ntawm cov kab mob raum thiab lub raum fibrosis

Cov txheej txheem kev yees duab muaj qhov zoo ntawm kev ua tsis muaj kev cuam tshuam thiab, yog li, yuav muaj kev nyab xeeb dua los ntsuas cov kev hloov pauv, muab cov ntaub ntawv rau ob lub raum thiab muaj peev xwm sib txuas ua haujlwm nrog cov ntaub ntawv morphological. Qhov kev nthuav dav tshaj plaws cuam tshuam txog kev kwv yees ntawm tus lej nephron, tag nrho lub raum ua haujlwm, fibrosis, thiab kev ua haujlwm tshiab magnetic resonance imaging (MRI), nrog rau cov txheej txheem ultrasound xws li diffusion-weighted MRI (DWI lossis DW-MRI), ntshav oxygenation theem. -dependent MRI (BOLD-MRI), perfusion MRI, hyperpolarized (HP) carbon 13 MRI (13C MRI) thiab contrast-enhanced ultrasound (CEUS).

Functional nephron tooj yog suav hais tias yog ib qho tseem ceeb rau kev txiav txim siab ntawm lub raum kev noj qab haus huv thiab kab mob kis thoob plaws lub neej [14, 15]. Hauv tib neeg, nephron tus naj npawb sib txawv thiab qhov txiaj ntsig nephron tsawg thaum yug los thiab / lossis poob ntawm nephrons thoob plaws lub neej yog cuam tshuam nrog rau mob raum [15]. Cov thev naus laus zis tshiab los ntsuas tus naj npawb nephron tab tom txhim kho, thiab kev ua haujlwm nephron tus lej muaj peev xwm siv tau los ua tus kws kho mob biomarker [14]. Nephron tooj, thaum siv los ua biomarker, tuaj yeem muab cov ntaub ntawv tseem ceeb hais txog kev mob raum thiab muab kev tshawb pom ntxov ntawm CKD qhov pib lossis kev ntsuam xyuas ntawm kev rov qab los tom qab mob raum mob, txhim kho kev ntsuam xyuas thiab kev ntsuam xyuas ntawm cov khoom siv pub dawb, kwv yees lub sijhawm muaj sia nyob, kwv yees qhov kev pheej hmoo ntawm cov tshuaj tiv thaiv nephrotoxicity, thiab pab tsim cov tswv yim rau kev siv tshuaj thiab tshuaj toxicity rau ntau hom tshuaj kho mob [14].

Cov txheej txheem tshiab tau pom zoo los ntsuas nephron tooj ex vivo hauv lub raum tsis zoo: cationized ferritin-enhanced MRI (CFE-MRI) [16], lub teeb daim ntawv microscopy tom qab kho qhov muag [17], thiab xam tomography (CT) [18]. Txawm li cas los xij, kev siv cov cuab yeej no hauv vivo thiab hauv tsev kho mob xav tau lawv tsis yog kev puas tsuaj thiab tsis cuam tshuam, thiab txog tam sim no tsuas yog CFE-MRI tau siv hauv vivo [14].

CFE-MRI siv ferritin ntim nrog hlau oxide [14]. Tom qab txhaj tshuaj, ferritin yog cationized thiab khi rau glomerular hauv qab daim nyias nyias. Kev sib sau ntawm ferritin nyob rau hauv lub glomeruli tso cai rau nws nrhiav pom, daim ntawv qhia ntawm tag nrho lub raum nyob rau hauv vivo, thiab co-localization ntawm glomeruli nrog rau lwm yam qauv xws li lub microvasculature. Txhawm rau txhawb kev siv nephron tus lej raws li qhov ntsuas ntsuas, cationized ferritin molecule ntawm CFE-MRI tau raug hloov kho los ua radiolabeled cationic ferritin (RadioCF), lub xov tooj cua siv hauv positron emission tomography (PET) los ua daim ntawv qhia kev ua haujlwm glomeruli hauv vivo hauv lub cev. cev [19]. RadioCF-PET ua kom muaj nuj nqis nephron loj hauv cov tsiaj thiab muaj peev xwm rau kev txhais lus kho mob [19]. Xov tooj cua-CF yog tsim los ntawm kev sib koom ua ke ntawm radioisotope, Cu-64, mus rau cationic ferritin (CF) thiab tau pom tias khi ua haujlwm glomeruli thaum muab tso rau hauv lub cev [19]. RadioCF PET tuaj yeem ua daim ntawv qhia thiab ntsuas thaj chaw ntawm kev ua haujlwm nephron poob ua rau nws yog ib qho cuab yeej kuaj mob uas tuaj yeem kwv yees kev nce qib CKD [14].

Daim duab 2: Novel diagnostic method in nephrology. CFE-MRI: cationized ferritin-enhanced MRI; RadioCF-PET: radiolabeled cationic ferritin-positron emission tomog raphy; CKD: mob raum mob; AKI:mob raum raug mob; GBM: glomerular qab daus daim nyias nyias; KRIS: Lub raum Risk Inflammatory Kos Npe; THSD7A: throm bospondin hom-1 domain-muaj 7A antibodies; NAD: nicotinamide adenine dinucleotide; FAT1: glomerular antigen-protocadherin FAT1; ESRD: kab mob raum kawg; DKD: mob ntshav qab zib raum; HST: hematopoietic qia cell transplantation; PCX: podocalyxin; KIM-1: lub raum raug mob molecule 1; TNF-: qog necrosis factor-; 8-OHdG: 8-oxo-7,8-dihydro- 2 -deoxyguanosine; L-FABP: daim siab-hom fatty acid binding protein; IGFBP-7: insulin-zoo li kev loj hlob zoo-binding protein-7; TIMP-2: cov ntaub so ntswg inhibitor ntawm metalloprotease-2; DIKI: mob raum raug mob; CNA35-CT: collagen-binding adhesion protein-35 CT; ESMA-raws li MRI: elastin-specific contrast agent MRI; DW-MRI: diffusion-weighted MRI; BOLD-MRI: ntshav oxygen qib-nyob ntawm MRI; HP-13C MRI: hyperpolarized carbon 13 MRI; ntxiv kos npe: zoo; kos npe rho tawm: qhov tsis zoo / kev txwv (qhia hauv xim liab).

MRI tau siv los ntsuas qhov ua haujlwm ntawm ob lub raum. Multiparametric MRI tuaj yeem ntsuas ntau yam ntawm lub raum ua haujlwm thiab vascularization [20]. Ib qho tshiab imaging modality yog sodium MRI. Piv nrog rau "ib txwm MRI," uas yog daim duab qhia ntawm hydrogen atoms hauv lub cev, sodium MRI yog daim ntawv qhia ntawm sodium atoms hauv lub cev. Lub raum muaj lub hauv paus gradient ntawm sodium concentrations los ntawm cortex mus rau medulla (corticomedullary sodium gradient) [21, 22]. Thawj txoj kev tshawb fawb ntawm sodium MRI ntawm tib neeg lub raum qhia tau hais tias sodium gradient nce linearly ntawm lub cortex mus rau medulla uas yog ua raws li los ntawm ib tug linear txo kom txog rau thaum lub raum pelvis [23, 24]. Txawm hais tias kev hloov pauv hauv sodium gradient tau pom nyob rau hauv ntau qhov kev kuaj mob thiab kev sim ua ntej, cov txheej txheem sodium MRI tsis nyob deb ntawm kev koom ua ke hauv kev kho mob [25–27] feem ntau yog vim tus nqi thiab kev koom tes hauv MRI recalibration thiab kev ua haujlwm. . Ib qho teeb meem loj ntxiv ntawm cov txheej txheem no, rau tam sim no, yog qhov tsis muaj qhov ua tau zoo ntawm kev tshawb pom nyob rau hauv ntau theem CKD thiab ntau yam kab mob raum.

Cov tswv yim tshwj xeeb tau tsim los ntsuas rau lub raum fibrosis thiab nws cov dynamics hauv ob lub raum ib txhij hauv vivo [28]. Cov no suav nrog fluorescent CNA35 CT, uas siv qhov zoo ntawm collagen-binding peptide, thiab elastin-specific contrast agent MRI (ESMA)-raws li molecular MRI ntawm elastin [28]. Piv txwv li, collagen-binding adhesion protein (CNA35) uas muaj asiab affinity rau homKuv thiab III collagen molecules tau siv los ua ib qho cuab yeej los pom cov collagen tso rau hauv cov ntsiab lus nas thiab muaj peev xwm siv tau rau tib neeg cov kev kawm raws li txoj kev tsis cuam tshuam ntawm kev ntsuam xyuas fibrosis [29, 30]. Ntawm qhov tod tes, ESMA-raws li MRI, uas yog ib qho me me peptide tshwj xeeb rau elastin, ib feem ntawm extracellular matrix, tau pom tias ua rau lub raum fibrosis hauv nas qauv nrog rau kev ua haujlwm ntawm kev kho mob los tiv thaiv fibrotic [31]. Cov txheej txheem no thaum kawg tseem yuav sim qhov muaj feem cuam tshuam ntawm kev kho mob los tiv thaiv fibrotic, qhov kev xav tau tam sim no.

Tsis tas li ntawd, cov tswv yim tshiab MRI tso cai rau tsim cov duab biomarkers uas tuaj yeem txhim kho kev tswj cov kab mob raum [20]. MRI ua rau kev ntsuas ntawm lub raum ntim, cov ntshav ntws hauv lub raum cov hlab ntsha, cov dej hauv lub raum, thiab cov ntaub so ntswg oxygenation [20]. DWI, los yog DW-MRI, tuaj yeem kuaj xyuas qhov hloov pauv ntawm cov dej molecules hauv cov ntaub so ntswg architecture [20]. Cov txheej txheem no tuaj yeem qhia txog kev hloov pauv hauv lub raum microstructure xws li lub raum fibrosis, cellular infiltration (inflammatory lossis qog) lossis edema nrog rau cov kev hloov hauv lub raum perfusion thiab hauv dej tuav hauv tubular compartment [20]. BOLD-MRI, uas ntsuas lub raum cov ntaub so ntswg deoxyhemoglobin qib voxel los ntawm voxel, yog ib qho kev cog lus los saib xyuas lub raum cov ntaub so ntswg oxygenation hauv tib neeg [32]. Nws tso cai rau saib xyuas kev hloov pauv hauv lub raum oxygenation lossis hloov pauv hauv capillary txaj microstructure. Tsis tas li ntawd, T2 tau hloov pauv los ntawm ntau lwm yam xws li hydration raws li txoj cai, kev noj zaub mov sodium, thiab cuam tshuam rau kev cuam tshuam [20]. Tsis tas li ntawd, HP 13C MRI yog cov cuab yeej muaj peev xwm, tsis yog tam sim no siv hauv tsev kho mob, rau kev ntsuas tsis muaj kev cuam tshuam ntawm oxidative kev nyuaj siab thiab mitochondrial pyruvate dehydrogenase kev ua haujlwm tom qab lub raum ischemia-reperfusion raug mob [33].

Tsis tas li ntawd, CEUS tau ua ib qho kev cog lus imaging modality rau lub raum mob. CEUS tsis muaj nephrotoxicity, ionizing hluav taws xob, thiab muaj peev xwm los soj ntsuam cov qauv txhim kho ntawm lub raum qhov txhab sai thiab nyob rau lub sijhawm [34]. Qee qhov kev siv tau zoo ntawm CEUS yog qhov sib txawv ntawm cov qog nqaij hlav, cov kab mob pseudo, thiab cov hlwv nyuaj; tus cwj pwm ntawm complex cysts nrog txawv malignant muaj peev xwm; thiab kev ntsuam xyuas ntawm qog ablation [34]. Microbubble contrast agents muaj kev nyab xeeb nrog qhov tsis zoo tshwm sim [34].

Cov txheej txheem no yog cov cuab yeej cog lus los ntsuas tus naj npawb nephron, ntau lub raum kev ua haujlwm thiab lub raum fibrosis thiab tej zaum yuav hloov mus rau kev siv tshuaj kho mob yog tias lawv muaj kev nyab xeeb, kev ua tau zoo, thiab kev tswj hwm kev cai raug tsim.

Biological kua biomarkers

Proteomics thiab metabolomics tsis ntev los no tau sim hauv thaj tsam ntawm nephrology nrog cov txiaj ntsig zoo thiab muaj txiaj ntsig. Qee zaum, cov npe proteomic lossis metabolomic lawv tus kheej yog siv los ua biomarkers. Hauv lwm tus, lawv yog cov cuab yeej siv los txheeb xyuas tus kheej biomarkers uas tau soj ntsuam siv cov txheej txheem ntau dua. Tsis tas li ntawd, ob qho tib si RNA thiab DNA hauv cov kua roj ntsha tuaj yeem ua cov cim biomarkers. Cov biomarkers no yuav tsum sib raug zoo nrog rau cov kab mob hauv lub raum, histopathology, kev loj hlob, tshwm sim los yog kab mob thaum ntxov, thiab tso cai rau kev ntsuas sai, tsis muaj kev cuam tshuam, thiab cov kev ntsuas tshwj xeeb nrog qhov siab thiab qhov tshwj xeeb.

Proteomic thiab metabolomic tsom xam rau kev tshawb nrhiav biomarkers

Pontillo thiab Mischak tau txheeb xyuas 273 urinary peptides uas txawv ntawm cov neeg mob CKD thiab cov neeg noj qab haus huv, uas yog cov cim CKD273 uas suav nrog cov khoom tawg ntawm collagen thiab cov proteins koom nrog kev mob thiab kho cov ntaub so ntswg, los ntawm kev siv capillary electrophoresis-mass spectroscopy (CE-MS) ntawm 230. CKD cov neeg mob thiab 379 cov kev tswj hwm [35, 36]. Cov kev tshawb fawb ntxiv tau hais txog qhov muaj peev xwm ua tau zoo tshaj plaws ntawm CKD73 hauv kev kwv yees thiab kev kuaj mob ntawm CKD dhau cov cim ib txwm ua rau tsab ntawv txhawb nqa ntawm US Food and Drug Administration (FDA). Raws li kev tshawb fawb hla ntu tau ua rau xyoo 1990 cov neeg koom, CKD273 ua tau zoo dua li cov cim ib txwm muaj thiab sib raug zoo dua li albuminuria nrog eGFR thiab zoo dua kwv yees kev nce qib CKD [37]. Cov kev tshawb pom zoo sib xws tau pom nyob rau hauv lwm txoj kev tshawb fawb ua rau 2087 cov neeg koom, uas CKD273 tau ntxiv rau qhov kev kwv yees ntawm CKD G3 tom qab suav rau hauv paus eGFR, albuminuria, thiab covariables [38]. Hauv kev sim randomized tswj hauv cov neeg mob ntshav qab zib tsis muaj albumin uria, CKD273 kwv yees kev txhim kho ntawm albuminuria [39]. Tsis tas li ntawd, tib CE-MS tsom xam ntawm ib qho qauv tso zis yuav raug siv los muab lwm cov cim peptidomics uas kwv yees qhov kev poob sai ntawm eGFR zoo dua li albuminuria hauv cov neeg mob uas tsis ua tiav eGFR cov qauv tam sim no rau CKD (piv txwv li tuaj yeem tso cai rau kev kuaj mob ua ntej. CKD dua li albuminuria) [40], lossis cuam tshuam nrog rau lub raum fibrosis raws li kuaj pom hauv lub raum biopsy [41] lossis muab cov ntaub ntawv qhia txog qhov tshwm sim ntawm CKD thiab nws cov kev mob tshwm sim [42, 43].

Lub raum Risk Inflammatory Signature (KRIS) suav nrog 17 cov proteins ncaj qha cuam tshuam rau kev mob thiab cuam tshuam nrog 10-xyoo kev pheej hmoo ntawm ESRD hauv cov kab mob raum mob ntshav qab zib [44]. Nyob rau hauv txoj kev tshawb no, 194 circulating inflammatory proteins tau raug soj ntsuam nyob rau hauv peb sib txawv cohorts muaj xws li hom 1 thiab 2 neeg mob ntshav qab zib, qhia tias 17 tshiab proteins enriched rau TNF Receptor Superfamily cov tswv cuab yog txuas mus rau thaum ntxov thiab lig lub raum tsis ua hauj lwm poob ua rau ESRD nyob rau hauv cov neeg mob ntshav qab zib. . Txawm hais tias lub hauv paus loj, xav tias yog cov qe ntshav dawb, ntawm cov KRIS cov proteins tseem tsis tau txiav txim siab, lawv cov tsos mob ntau xyoo ua ntej qhov pib ntawm ESRD zoo li muaj feem cuam tshuam rau kev tsim tawm ntau dhau, uas cuam tshuam rau lub raum tshem tawm. Ntxiv rau lawv lub luag haujlwm kwv yees hauv ESRD, KRIS cov proteins muab qhov muaj peev xwm kho tau qhov cuam tshuam raws li qhov ua pov thawj los ntawm kev sim tshuaj ntsuam xyuas hauv ib qho ntawm peb pawg neeg ua pov thawj pom tias muaj kev poob qis hauv albuminuria raws li qhov poob ntawm KRIS cov proteins hauv cov lus teb rau {{7} }lub lim tiam sim nrog 4 mg ntawm baricitinib, JAK-1/2 inhibitor [45]. Tsis tas li ntawd, qee cov metabolites ntawm nicotinamide adenine dinucleotide (NAD) tsis ntev los no tau cuam tshuam nrog rau mob raum raug mob (AKI) txaus ntshai [46].

Muaj ntau qhov kev sim tshuaj tsis tu ncua (NCT01550393, NCT02743273, NCT00690586, NCT04851145) tshawb xyuas lub luag haujlwm ntawm proteomics thiab metabolomics hauv thaj tsam ntawm nephrology. Txawm li cas los xij, cov kev sim no yuav tsum ua kom pom tau tias cov tshuaj proteomics lossis metabolomics biomarkers muab cov ntaub ntawv ntxiv txog cov pa biomarkers uas muaj feem cuam tshuam rau kev kho mob thiab tuaj yeem hloov kho qhov kev txiav txim siab ntawm tus nqi zoo. Nws yog ib qho tseem ceeb uas yuav tsum tau hais txog tias cov kev tshawb fawb tshawb xyuas cov biomarkers tshiab yuav tsum tsis yog ib qho kev tshawb nrhiav tab sis kuj yog ib qho kev ywj pheej (thib ob) validation cohort.

Muaj ntau qhov kev sim tshuaj tsis tu ncua (NCT01550393, NCT02743273, NCT00690586, NCT04851145) tshawb xyuas lub luag haujlwm ntawm proteomics thiab metabolomics hauv thaj tsam ntawm nephrology. Txawm li cas los xij, cov kev sim no yuav tsum ua kom pom tau tias cov tshuaj proteomics lossis metabolomics biomarkers muab cov ntaub ntawv ntxiv txog cov pa biomarkers uas muaj feem cuam tshuam rau kev kho mob thiab tuaj yeem hloov kho qhov kev txiav txim siab ntawm tus nqi zoo. Nws yog ib qho tseem ceeb uas yuav tsum tau hais txog tias cov kev tshawb fawb tshawb xyuas cov biomarkers tshiab yuav tsum tsis yog ib qho kev tshawb nrhiav tab sis kuj yog ib qho kev ywj pheej (thib ob) validation cohort.

Tsis tas li ntawd, ntau yam tshiab biomarkers tau txheeb xyuas tsis ntev los no, qee zaum siv proteomics, txawm hais tias lawv nyob rau ntau theem ntawm kev txhais lus rau lub tsev kho mob [47]. Ntau tshaj 40 qhov muaj peev xwm biomarkers tau tshwm sim nyob rau xyoo tas los no thiab feem ntau tuaj yeem txheeb raws li lawv lub koom haum nrog cov yam ntxwv xws li glomerular raug mob [podocalyxin (PCX)], tubular raug mob [mob raum raug mob molecule 1 (KIM-1)], o [cov qog necrosis factor- (TNF-), TNF receptors-1 thiab -2) [48]] thiab oxidative stress [8-oxo- 7,8-dihydro - 2 -deoxyguanosine (8-OHdG)] [47]. CKD biomarkers tuaj yeem txheeb xyuas los ntawm ntau txoj hauv kev xws li cov txheej txheem fluorescent immunoassay, kua chromatography-mass spectrometry, kua chromatography-mass spectrometry, high-performance kua chromatography (HPLC), thiab enzyme-linked immunosorbent assay (ELISA) 47] ib. Tsis tas li ntawd, microfluidics tso cai rau lub sijhawm ua piv txwv luv luv nrog rau cov hneev taw me me, kev ua haujlwm tsis siv neeg thiab kev hloov pauv siab, thiab tej zaum yuav muaj peev xwm muab cov cuab yeej muaj zog, muaj txiaj ntsig zoo, thiab yooj yim-rau-ua haujlwm rau kev kuaj mob ntxov ntawm CKD thiab lwm yam kab mob. xwm txheej [47].

Membranous nephropathy yog feem ntau ua rau nephrotic syndrome hauv cov neeg laus thiab cov neeg mob hematopoietic stem cell transplant (HST). Lub flurry ntawm autoantigens tau raug txheeb xyuas tsis ntev los no, ua raws li cov lus piav qhia ntawm anti-phospholipase A2 receptor (PLA2R) cov tshuaj tiv thaiv, biomarker uas raws li cov lus qhia tam sim no tuaj yeem hloov lub raum biopsy hauv cov neeg mob membranous nephropathy [49]. Anti-protocadherin FAT1 cov tshuaj tiv thaiv muaj nyob hauv ntau dua 80% ntawm cov neeg mob membranous nephropathy tom qab HST [50]. Cov neeg mob uas muaj anti-PLA2R antibody-negative thawj membranous nephropathy tej zaum yuav muaj anti-thrombospondin hom-1 domain-muaj 7A antibodies [51, 52]. Tsis tas li ntawd, cov tshuaj tiv thaiv nephrin tau kuaj pom los ntawm kev tshawb fawb serological thiab immunohistochemical hauv ib pawg ntawm cov neeg mob biopsy-pov thawj tsawg kawg nkaus hloov cov neeg mob [53].

Lub teb ntawm biomarkers ntawm AKI kuj tseem muaj zog heev; urinary insulin-zoo li kev loj hlob zoo-binding protein-7 (IGFBP-7) thiab cov ntaub so ntswg inhibitor ntawm metalloprotease-2 (TIMP-2) yog tam sim no nyob rau hauv kev kho mob siv nyob rau hauv lub npe hom Nephrocheck [47, 54]. Lub raum tubular raug mob ua rau tso ntshav thiab zis biomarkers [55]. Urinary KIM-1, lub siab-hom fatty acid binding protein (L-FABP), IGFBP-7 thiab TIMP-2 raug tso tawm los ntawm cov tubule ze ze, hos uromodulin (UMOD) yog secreted los ntawm cov Loop ntawm Henle thiab neutrophil gelatinase-associated lipocalin (NGAL) originates los ntawm distal tubules [55]. Cov biomarkers no tuaj yeem ua rau thaj chaw tshwj xeeb ntawm cov tubules raug mob. Biomarkers koom nrog kev mob, kho, thiab fibrosis [55] kuj tuaj yeem kwv yees qhov kev hloov pauv ntawm AKI mus rau CKD, pab kom paub qhov txawv ntawm lub raum tsis ua haujlwm thiab raug mob, qhia AKI kev tswj hwm, thiab txhim kho kev kuaj mob ntawm cov kab mob xws li mob interstitial nephritis [55]. Tsis tas li ntawd, qee qhov biomarkers tau npaj siv rau hauv kev sim tshuaj ntawm AKI thiab tuaj yeem coj kev tswj hwm hauv qee qhov chaw kho mob. Lub Raum Precision Tshuaj Project yog ib qho kev siv zog txuas ntxiv los tsim lub raum cov ntaub so ntswg atlas thiab nce kev siv biomarkers los ntsuas nephron noj qab haus huv [55].

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