mwwXaiv lus
Tsev / Kev paub / Ntsiab lus

Kev paub

Ib Novel Multi-Biomarker Assay Rau Tsis-Invasive Quantitative Monitoring Of Kidney Injury

Feb 22, 2022

Drew Watson1, Yausua YC Yang1,2,3ua al


Abstract:Cov qauv kev saib xyuas tam sim no rauraummuaj nuj nqi, proteinuria, thiab serum creatinine (SCr) yog qhov tsis zoo ntawm cov theem pibraumkab mob. Kev ntsuas uas tuaj yeem ntes taumob ntevraumkab mobnyob rau hauv nws cov theem ua ntej yog xav tau los pab kho kev cuam tshuam thiab txo qhov tshwm sim tsis zoo ntawmmob ntevraumkab mob. Peb tau tsim qhov Kev Ntsuam Xyuas Kev Mob Raum (KIT) thiab KIT Score tshiab raws li kev ntsuas sib xyaw thiab kev siv tau ntawm ntau lub biomarkers thoob plaws ib qho tshwj xeeb ntawm 397 cov qauv zis. Qhov kev sim no yog ua los ntawm cov zis kuaj uas yuav tsum tsis muaj kev ua haujlwm ntawm qhov chaw ntawm kev sau thiab tsis muaj lub hom phiaj sib txuas lossis nthuav dav. Peb nrhiav kom paub tseeb tias qhov kev xeem KIT ua ntej, KIT Score, thiab cov chaw kho mob muaj feem cuam tshuam nrog tsimmob ntevraumkab mob(CKD) thiab tuaj yeem muab cov ntaub ntawv kwv yees txog kev raug mob raum thaum ntxov saum toj no thiab dhau ntawm cov proteinuria thiab kev ntsuas lub raum ua haujlwm ib leeg. Kev txheeb xyuas txheeb cais thoob plaws rau 6 DNA, protein, thiab cov cim metabolite tau ua nyob rau ntawm cov khoom seem ntawm cov zis tso zis nrogCKDuas tau ntsib kev soj ntsuam kev ua tau zoo ntawm cov neeg mob uas tuaj koom cov chaw kuaj mob hauv University of California, San Francisco (UCSF) uas yog ib feem ntawm kev tshawb fawb txuas ntxiv IRB-pom zoo. Cov txheej txheem suav nrog suav nrog kev xaiv cov neeg mob uas tau lees paubCKDthiab tswj kev noj qab nyob zoo; Cov txheej txheem cais tawm suav nrog cov ntaub ntawv tsis tiav lossis ploj lawm rau cov qauv kev faib tawm, kev thauj mus los qeeb hauv kev thauj / ua cov qauv tso zis lossis cov qauv ntim qis, thiab mob raum raug mob. Multivariate logistic regression ntawmraumraug mobCov xwm txheej thiab qhov muaj feem cuam tshuam cov txheeb cais tau siv los ntsuas qhov kev koom tes ntawm KIT Score rau kev kwv yees ntawmraumraug mobraws li txoj cai thiab theem ntawm CKD nrog rau kev ntsuam xyuas qhov muaj peev xwm pab tau ntawm KIT Score rau kev tshawb pom ntawm theem pibCKDsaum toj no thiab dhau ib txwm ntsuas ntawm lub raum ua haujlwm. Cov qauv tso zis tau ua tiav los ntawm cov khoom siv tshuaj tiv thaiv kab mob rau kev ntsuas cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, tag nrho cov protein, thiab creatinine. KIT Score thiab stratified KIT Score Risk Group (siab piv rau qis) muaj qhov rhiab heev thiab qhov tshwj xeeb rau kev kuaj pom ntawm lub raum raug mob (zoo lossisCKD) ntawm 97.3 feem pua ​​(95 feem pua ​​CI: 94.6–99.3 feem pua) thiab 94.1 feem pua ​​(95 feem pua ​​CI: 82.3–100 feem pua). Tsis tas li ntawd, hauv cov neeg mob uas lub raum ua haujlwm tsis zoo (kwv yees glomerular filtration rate (eGFR)> 90), KIT Score qhia meej meej rau cov neeg uas muaj feem cuam tshuam rauCKD, uas tsis tuaj yeem kuaj pom los ntawm eGFR lossis proteinuria (p < 0.001).="" kit="" score="" uncovers="" lub="" nra="" ntawm="" lub="" raum="" raug="" mob="" uas="" tseem="" tsis="" tau="" lees="" paub,="" qhib="" qhov="" rooj="" rau="" kev="" kuaj="" pom="" ua="" ntej,="" kev="" cuam="" tshuam,="" thiab="" kev="" khaws="" cia="" ntawm="" lub="" raum="" ua="">

Ntsiab lus:KIT Assay; mob ntevraumkab mob; biomarker; tsis-invasive; tso zis; eGFR; cfDNA

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

cistanche can treat Kidney Injury

1. Taw qhia

Ntevraumkab mob(CKD) yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb, nrog rau lub nra thoob ntiaj teb ntawm 850 lab tus tib neeg.CKDTam sim no tau raug lees paub tias yog "mob sib kis", vim tias feem ntau cov neeg mob uas muaj theem pib ntawm CKD (~ 11 feem pua ​​​​ntawm cov neeg laus hauv ntiaj teb) mus tsis tau lees paub, vim lawv tsis muaj tsos mob thiab tsis paub txog lawv txoj kev pheej hmoo siab rau teeb meem plawv, kab mob. , tsev kho mob, thiab lub raum tsis ua haujlwm. Yog li, CKD feem ntau tsis suav tias yog qhov teeb meem loj rau kev noj qab haus huv, txawm tias nws cuam tshuam rau ob npaug ntawm cov neeg mob ntshav qab zib (422 lab) thiab ntau dua 20 npaug ntawm cov neeg mob qog noj ntshav (42 lab) lossis HIV / AIDS (36.7 lab).

CKD is defined as a reduced renal reserve, persisting for >3 lub hlis thiab/lossis kev kuaj mob ua ntej ntawm ib tus mob uas paub txog kev pheej hmoo rauraumdamage [1]. CKD is defined in a five-stage classification system for the assessment of kidney injury as patients advance towards the need for dialysis or transplantation [2]. The current standard of care tests, the blood-based serum creatinine (SCr) assay (and its use to calculate the estimated glomerular filtration rate or eGFR [3]) and protein in the urine, detect CKD 3–5 (eGFR of s60 mL/min/1.73 m2 of body surface area). However, most cases of CKD 1–2 (CKD >60 mL / min / 1.73 m2 ntawm lub cev saum npoo av) mus tsis pom. eGFR muaj qhov tsis zoo rau kev tshawb pom CKD thaum ntxov, vim tias qhov rov ua dua ntawm lub raum cia qhov ncauj qhov ntswg qhov nce thaum ntxov hauv SCr. Lub raum biopsies, feem ntau tshwm sim nrog cov theem siab tshaj ntawm CKD, muaj nuj nqis los ntsuas cov kab mob, tab sis muaj kev cuam tshuam, kim [4], thiab tsis tuaj yeem siv rau kev soj ntsuam xyuas ntawm CKD.

Ntau qhov tshwm sim thiab cov xwm txheej txaus ntshai pib lub cascade ntawmraumkev puas tsuaj nyob rau hauvCKD, nrog rau kev mob raum tsis ua haujlwm (CKD 5). Muaj ntau dua 10 lab tus tib neeg thoob plaws ntiaj teb xav tau kev kho raum raum nrog kev txhawb nqa mus ntev los ntawm kev lim ntshav lossis hloov lub raum. Txawm hais tias kev lim ntshav thiab hloov pauv hloov lub raum ua haujlwm, lawv ob leeg tseem muaj kev cuam tshuam los ntawm kev cuam tshuam tsis zoo rau tus neeg mob morbidity thiab kev tuag. Kuj tseem muaj kev cuam tshuam ntawm CKD ntawm lwm lub cev hauv lub cev;CKDCov neeg mob muaj kev pheej hmoo ntau dua ntawm kev kis kab mob, mob plawv tuag, thiab mob qog noj ntshav [5].

Kev tshawb pom ntxov ntawm lub raum puas yog qhov tseem ceeb, raws li kev kho mob hauvCKD1-2 tuaj yeem ua rau lub raum khaws cia los ntawm kev thim rov qab lossis ua kom qeeb ntawm lub raum puas [6]. Tam sim no, cov kev ntsuam xyuas cov zis tsis tuaj yeem kuaj pom qhov qis ntawm lub raum raug mob [7–14] thiab feem ntau tau raug soj ntsuam hauv mob raum raug mob (AKI), nrog kev ntxub ntxaug rau CKD [9]. Yog li, nws yog ib qho tseem ceeb uas yuav tsum tau ua kom tsis txhob muaj qhov xav tau los txhim kho qhov kev xav tau, muaj nuj nqis, tsis muaj kev cuam tshuam los kuaj xyuas CKD 1-3. Kev kuaj pom ntxov thiab kev kho mob ntxov ntawm CKD yuav txo tau lub nra ntawm kab mob thoob ntiaj teb thiab txo cov nyiaj txiag loj ntawm cov peev nyiaj kho mob hauv tebchaws [15–21].

The primary aim of this study was to perform an assessment of multiple novels and known urine biomarker measurements to conduct an inexpensive, portable assay, called the Kidney Injury Test (KIT) in consecutive patients presenting with CKD at a large tertiary health care system, and develop and independently validate a quantitative KIT Score to reflect the diferent CKD stages. The KIT assay performance was also directly compared to the current standard of care tests (eGFR and proteinuria). A secondary aim was to explore the accuracy of the KIT assay to detect and quantitate kidney injury in CKD 1–2, i.e., subjects with normal eGFR (>60) tab sis nrog cov kev pheej hmoo ua rau CKD. Daim ntawv tshaj tawm no piav qhia txog cov txheej txheem ntawm kev xaiv biomarker, kev txhim kho algorithm, thiab kev lees paub ywj pheej ntawm KIT Score raws li kev tshuaj ntsuam xyuas tshiab rau kev ntsuam xyuas thiab kev txheeb xyuas ntawm ob qho tib si thaum ntxov thiab lig.raumkev puas tsuaj.

Cistanche deserticola prevents kidney disease and injury

2. Ntu kev sim

2.1. Kev xaiv tus neeg mob

Cov zis seem, qhov chaw tso zis tau sau los ntawm 1169 tus neeg mob raws li cov neeg mob los ntawm cov chaw kuaj mob hauv University of California, San Francisco (UCSF), ntau dua 3 lub hlis, txij lub Kaum Hli 2016 txog Lub Ib Hlis 2017, ua ib feem ntawm kev kuaj mob niaj hnub ntawm Parnassus thiab Lub Hom Phiaj Bay cov chaw kuaj mob hauv tsev kawm ntawv. Cov qauv xaiv rau kev kuaj mob CKD tau ua kom muaj txiaj ntsig zoo los ntawm kev xaiv cov qauv zis tau los ntawm nephrology, ntshav qab zib, lossis cov chaw kho mob plawv ntawm UCSF. Txhawm rau pab txhawb lub zog ntawm cov ntaub ntawv, txoj kev tshawb fawb tau txhawb nqa rau cov neeg mob uas muaj kev pheej hmoo siab mob raum, siv cov txheej txheem hauv qab no: tus neeg mob tau kuaj pom tus mob CKD (ICD10 code N18 [22]), tsis muaj kev kuaj mob CKD tab sis tam sim no kuaj mob ntshav qab zib. , mob ntshav siab lossis kab mob autoimmune, tsis muaj CKD tab sis tsev neeg keeb kwm zoo ntawm CKD, tsis muaj CKD tab sis hnub nyoog tshaj 60 xyoo lossis los ntawm haiv neeg tsawg. Cov neeg mob nrog AKI tsis suav nrog hauv qhov kev tshawb fawb no, nrog rau cov laj thawj hauv qab no: (1) qhov kev tshawb fawb thawj zaug ntawm KIT yog tsom rau kev txhim kho thiab kev siv tau ntawm qhov ntsuas qhov ntau thiab ua haujlwm ntawm KIT Score nyob rau hauv ib qho kev mob mus ntev ntawm kev mob raum. AKI muaj qhov sib txawv ntawm qhov sib txawv nrog qhov pib mob thiab kev daws teeb meem; (2) AKI tej zaum yuav muaj qhov ua tiav lossis tsis tiav ntawm kev raug mob, yog li KIT Score txo tom qab kev daws teeb meem ntawm AKI yuav dhau los ua kev kho mob txhais tau thaum KIT Score ranges tau teeb tsa hauv daim ntawv no rau cov theem sib txawv ntawm CKD; (3) AKI yog ib qho ua rau muaj kev pheej hmoo ntawm CKD, tab sis feem ntau ntawm cov neeg mob CKD, xws li ntshav qab zib thiab kub siab, tsis pib nrog AKI. Ib qho kev kawm ntawm KIT Score hauv AKI yog npaj raws li kev tshawb nrhiav tom qab.

Rau lub hom phiaj ntawm KIT Score txoj kev loj hlob, qhov cuam tshuam ntawm CKD lossis qhov ua rau muaj kev pheej hmoo rau CKD tau raug ntes los ntawm cov ntaub ntawv kho mob hluav taws xob (EHR), suav nrog cov pej xeem sib txawv thiab SCr, kom tso cai suav ntawm eGFR [23]. Rau txhua tus neeg mob, qhov tshwm sim thiab ua rau mob raum tau raug lees paub los ntawm kev tshuaj xyuas cov ntaub ntawv kho mob thiab chaw kuaj mob. Feem ntau ua rau CKD nyob rau hauv pawg no yog: cov kab mob tiv thaiv kab mob uas tuaj yeem ua rau lub raum raug mob (xws li lupus nephritis, rheumatoid mob caj dab, Sjogren's syndrome), kub siab, ntshav qab zib (hom 1 thiab 2), kab mob glomerular (cov mob no yog Kev kuaj ntshav tau lees paub nrog IgA nephropathy, membranoproliferative glomerulonephritis lossis focal segmental glomerulosclerosis) thiab obstructive uropathy (neurogenic zais zis, posterior urethral li qub, thiab hydronephrosis). Hauv CKD tus neeg mob pawg, 74.8 feem pua ​​​​ntawm cov neeg mob muaj 2 lossis ntau qhov kev kuaj mob uas yuav cuam tshuam rau CKD kev loj hlob thiab kev loj hlob, thaum 13.3 feem pua ​​​​ntawm cov neeg mob muaj ntshav qab zib thiab kub siab ua rau ob lub raum raug mob thaum tsis muaj kev kuaj mob ntawm CKD. , qhov cuam tshuam ntawm qhov muaj feem ntau ntawm cov kab mob sib kis no hauv cov pej xeem. Qhov laj thawj ntawm CKD tsis raug lim, thiab txhua qhov ua rau CKD raug ntes.

To avoid degradation of the biomarkers in the KIT assay, urine samples were either processed within an hour of collection or stored at 4 C and processed within 24 h. Samples were discarded or not included for analysis in this study if the sample volume was less than 2 mL, there were insufficient data to confirm patient CKD diagnosis, or there was a>24 teev qeeb hauv kev ua qauv vim yog vim li cas logistical. Tom qab cov txheej txheem lim dej saum toj no, peb tau xaiv qhov kawg ntawm 343 cov qauv zis tshwj xeeb los ntawm 343 tus neeg mob. Peb kuj tau txais cov qauv tso zis ntxiv los ntawm 54 qhov kev tswj hwm kev noj qab haus huv xaiv los ntawm cov neeg tuaj yeem pab dawb uas muaj kev noj qab haus huv zoo, nrog rau SCr ib txwm muaj, tsis muaj proteinuria, thiab tsis muaj CKD uas muaj feem cuam tshuam. Txoj kev tshawb no tau ua raws li Cov Lus Tshaj Tawm ntawm Helsinki thiab Istanbul thiab tau txais kev pom zoo los ntawm lub koom haum saib xyuas pawg thawj coj saib xyuas ntawm UCSF (IRB 16-21108) thiab qhov yuav tsum tau muaj kev pom zoo raug zam los ntawm IRB.

2.2. KIT Assay Methods

2.2.1. Qauv ua

Cov zis kuaj tau raug sau rau hauv cov thawv tsis muaj menyuam (ntxuav ntes, nruab nrab-kwj tsis muaj), tsis hais txog micro- lossis macroscopic hematuria lossis proteinuria. Cov zis kuaj tau centrifuged ntawm 2000 × g rau 30 min ntawm 4 oC. Tus supernatant tau cais tawm ntawm cov zis pellet uas muaj cov hlwb thiab cov khib nyiab ntawm tes. Cov pH ntawm cov supernatant tau hloov mus rau 7.0 siv Tris–HCl thiab khaws cia ntawm _80oC hauv UCSF Biorepository kom txog thaum kev tshuaj xyuas ntxiv.

2.2.2. KIT Biomarkers

KIT inputs normalized ntsuas ntawm 6 thawj cov zis biomarkers. Thawj biomarker yog cell-free DNA (cfDNA): raws li ib qho kev ntsuas ntawm tag nrho apoptotic lub nra ntawm lub raum raug mob [24], ntsuas los ntawm ib tug proprietary 5' biotinylated oligonucleotide complementary chemiluminescent immunoprobe rau tshwj xeeb hom phiaj cfDNA fragments nyob rau hauv lub raum raug mob [25] Txoj hauv kev no kov yeej cov kev txwv ntawm kev siv sijhawm ua piv txwv, tus nqi PCR amplification [26], SNP nrhiav pom ([27,28] lossis DNA sequencing method [29], txwv tsis pub ua haujlwm los ntsuas cfDNA hauv ntshav [27,30]. ELISA-measured markers suav nrog methylated cfDNA (m-cfDNA) los kho qhov feem ntawm cfDNA uas tej zaum yuav cuam tshuam ntau dua rau lub raum parenchymal raug mob [31,32]; Cov cim ntawm lub raum tubular raug mob [38,39]; tag nrho cov protein, raws li ib tug lig marker ntawm glomerular raug mob [40,41]; thiab creatinine, raws li ib tug normalizing marker raws li nws muaj peev xwm cuam tshuam los ntawm lub cev loj, khoom noj khoom haus thiab / los yog hydration thiab siv. kom tsis txhob muaj qhov xav tau rau lub sijhawm sau zis [42,43].

2.3. Kev txheeb cais

2.3.1. KIT Score Development

Random sampling tau siv los faib cov 397- neeg mob cohort rau hauv kev cob qhia (n=233, nrog 37 kev tswj kev noj qab haus huv) teeb tsa, stratified los ntawm lub raum raug mob. Random hav zoov qauv tau siv los txheeb xyuas kev sib raug zoo ntawm cov cim sib txawv rau kev tshawb pom ntawm CKD nrog rau siab rhiab heev. Cov qauv kev kwv yees tau raug cob qhia siv cov kev txheeb cais thiab kev kawm tshuab rau kev txhim kho KIT Score algorithm, hla tag nrho rau 6 tus neeg xaiv DNA thiab cov protein biomarkers thiab ntau qhov kev faib tawm ntawm cov kev ntsuas ntsuas no tau ua raws li kev txheeb xyuas qhov pib los ntawm kev suav nrog SCr thiab kev pheej hmoo paub ntxiv. Kev hloov pauv rau CKD xws li haiv neeg, poj niam txiv neej, thiab hnub nyoog. Thaum kawg, tus qauv yooj yim linear suav nrog cov txiaj ntsig tau muab faib rau hauv KIT Score nrog rau qhov pib ntxiv rau qhov kev ntsuam xyuas ntawm qhov qis thiab muaj kev pheej hmoo siab ntawm CKD.

2.3.2. KIT Score Validation

Ib qho kev lees paub ywj pheej ntawm 164 tus neeg mob, nrog 17 kev tswj hwm kev noj qab haus huv, tau siv tom qab siv los ua pov thawj qhov kev ntsuam xyuas ua ntej KIT thiab KIT Score. Logistic regression tau siv los sib piv cov qauv (tag nrho) nrog cov qauv kev kuaj xyuas tam sim no, cov zis protein ib leeg, thiab eGFR. Tus nqi p-tus nqi < 0.01="" rau="" qhov="" sib="" piv="" qhov="" piv="" txwv="" tau="" suav="" tias="" yog="" qhov="" tseem="" ceeb.="" logistic="" regression="" analyses="" tau="" ua="" los="" ntsuas="" qhov="" tseeb="" ntawm="" cov="" qhab="" nias="" ua="" ntej="" kit="" score="" pib="" rau="" categorical="" (qis="" thiab="" siab)="" kit="" score="" risk="" pawg.="" qhov="" rhiab="" heev="" thiab="" qhov="" tshwj="" xeeb="" ntawm="" qhov="" ua="" tau="" kom="" muaj="" nuj="" nqis="" thiab="" zoo="" kit="" score,="" nrog="" rau="" 95="" feem="" pua="" ​​​​ntawm="" kev="" ntseeg="" siab,="" raug="">

T-test and logistic regression were used to compare the pre-defined KIT Score and model patient status (individuals predisposed to CKD versus healthy subjects), to assess its ability to distinguish subjects with early stages of CKD (eGFR 60–90, CKD 2) and normal eGFR but with predisposing risk factors for developing kidney damage (>90, CKD 1), los ntawm cov neeg ua haujlwm pab dawb noj qab haus huv (eGFR> 90) uas tsis paub txog qhov muaj feem yuav tshwm sim. P-tus nqi <0.01 tau="" suav="" tias="" yog="" qhov="" tseem="">

3. Cov txiaj ntsig

Ntawm 1169 tus neeg mob uas tau txais thiab kuaj cov zis, 201 cov qauv ua tau raws li cov txheej txheem cais tawm ntawm cov zis ntim qis thiab tau sim los ntawm kev tshuaj xyuas ntxiv, tawm hauv 968 tus neeg mob (cov pej xeem hauv Table 1). Kev faib tawm ntawm cov proteinuria hauv cov neeg mob 968 no (0 rau 5469.73; qhov nruab nrab (IQR) ntawm 4.69 (0–39.11) mg / mmol) thiab qhov ntau ntawm eGFR (xam rau txhua tus neeg mob CKD [23] (Daim duab 1C) ) qhia tias peb tau ntes cov kab mob CKD (Daim duab 1A). Los ntawm pawg neeg no, 397 tus neeg mob tshwj xeeb thiab cov qauv muaj sia nyob ntawm cov txheej txheem cais tawm (saib Cov Txheej Txheem). Etiologies ntawm lawv lub raum raug mob muaj ntau yam kab mob, nrog rau kev kub siab ua rau muaj txiaj ntsig rau 42 feem pua ​​​​ntawm cov neeg mob (Daim duab 1B). Ntau tshaj 60 feem pua ​​​​ntawm cov neeg mob muaj ntau tshaj ib qho ua rau lawv lub raum raug mob. Muab hais tias qhov no yog qhov tseeb rau cov neeg mob CKD feem ntau, tshwj xeeb tshaj yog thaum lawv nce mus rau theem tom ntej ntawm CKD, KIT Score tau ua qauv los kuaj pom kev raug mob raum tsis hais txog qhov tshwm sim. Txawm hais tias proteinuria yog tus qauv kub tam sim no rau kev ntsuas tsis muaj kev cuam tshuam ntawm lub raum raug mob, tsis muaj kev sib raug zoo ntawm eGFR thiab cov zis protein / creatinine piv (R2=0.0087) thiab, raws li qhia los ntawm lwm cov neeg tshawb xyuas [44 ], proteinuria tsis zoo ntawm categorizing theem ntawm CKD (Daim duab 2).

Table 1. Demographics and presenting features of the study cohort 1.

Lub hom phiaj tseem ceeb ntawm txoj kev tshawb fawb no yog los tsim kom muaj kev sib xyaw KIT ​​Score scaling los ntawm {{{0}}} (tsis tshua muaj kev pheej hmoo) mus rau 100 (muaj kev pheej hmoo siab) thiab yav tom ntej ntsuas qhov muaj peev xwm ntawm KIT Score ntau rau kev kuaj pom kev raug mob raum. nrog rau qib siab ntawm rhiab heev thiab tshwj xeeb. Peb qhia tau hais tias, txawm hais tias tam sim no kev ntsuas ntawm lub raum ua haujlwm (eGFR thiab proteinuria) yog qhov kwv yees ntawm CKD late-stage CKD (Table 2), qhov ntau ntawm KIT Score scaling ntawm 0 (tsawg tshaj plaws) mus rau 100 (siab tshaj plaws) muab cov ntaub ntawv kwv yees.

Figure 2. Cohort characteristics. Receiver operating characteristic curves and heat maps for kidney injury. (A) Receiver operating characteristic (ROC) curves for detection of kidney injury based on the KIT Score (training—orange and validation—green), serum creatinine (purple) and protein/creatine (aqua).

ntawm lub raum raug mob saum toj no thiab dhau ntawm cov proteinuria thiab lub raum ua haujlwm ib leeg (xws li qhov piv txwv x {{0}}.507, p-value < 0.0001),="" thiab="" ua="" tau="" zoo="" tshaj="" li="" cov="" qauv="" kev="" kuaj="" mob="" tam="" sim="" no="" (table="" 3).="" cov="" zis="" creatinine="" yog="" siv="" rau="" normalization="" lub="" hom="" phiaj="" nyob="" rau="" hauv="" lub="" kit="" algorithm,="" thiab="" tswj="" rau="" diurnal="" thiab="" hydration="" variations="" (yog="" li="" obviating="" qhov="" yuav="" tsum="" tau="" rau="" tej="" lub="" sij="" hawm="" tso="" zis="" sampling)="" thiab="" tsis="" tseem="" ceeb="" rau="" ckd="" theem="" nyob="" rau="" hauv="" multivariate="" tsom="" xam="" (p-value="0.">

Table 2. Multivariate logistic regression of kidney injury status as assessed by SCr, eGFR and proteinuria.

We also developed a qualitative KIT Score, an approach that can have important implications for population kidney risk assessment. A pre-defined risk threshold of 18.5 was established in the training data, allowing the separation of the KIT Scores into low (s18.5) and high risk (>18.5) pawg ntawm lub raum raug mob. Qhov no tau lees paub nyob rau hauv qhov kev ntsuam xyuas los muab cov ntaub ntawv kwv yees ntawm lub raum raug mob saum toj no thiab dhau ntawm cov proteinuria thiab eGFR (feem ntau yog x=44.244, p-value <>

Qhov kwv yees rhiab heev thiab qhov tshwj xeeb ntawm KIT Score rau kev kuaj pom ntawm CKD yog 97.3 feem pua ​​(bootstrap 95 feem pua ​​CI: 94.6, 99.3 feem pua) thiab 94.1 feem pua ​​(bootstrap 95 feem pua ​​CI: 82.3, 100 feem pua), feem. Hauv qhov sib piv, qhov rhiab heev thiab qhov tshwj xeeb ntawm cov proteinuria yog 46.9 feem pua ​​(bootstrap 95 feem pua ​​CI: 38.8, 55.8 feem pua) thiab 88.2 feem pua ​​(bootstrap 95 feem pua ​​CI: 70.6, 100 feem pua), feem, rau tib cov qauv. Ib yam li ntawd, qhov rhiab heev ntawm SCr yog 65.6 feem pua ​​(bootstrap 95 feem pua ​​CI: 57.4, 73.8 feem pua). Qhov kev kwv yees ntawm qhov tsis zoo thiab qhov zoo kwv yees qhov tseem ceeb ntawm KIT Score yog nyob ntawm tus nqi ntawm tus kab mob, yog li qhov kev pheej hmoo ntawm ntshav siab tuaj yeem siv ua piv txwv. Qhov tshwm sim ntawm kev kub siab nyob rau hauv cov pej xeem hauv Teb Chaws Asmeskas yog kwv yees li 33 feem pua. Yog li ntawd, qhov kwv yees kwv yees qhov zoo thiab qhov tsis zoo ntawm tus nqi KIT Score rau ntshav siab yuav yog ~ 89.1 feem pua ​​thiab 98.2 feem pua.

Peb qhia txog kev koom tes ntawm tus kheej biomarkers rau KIT Score hauv qab no (Table 4). Qhov ntau ntawm cfDNA hauv cov zis yog qhov sib txawv ntawm ntau hom kab mob raum thiab tsis sib cuam tshuam nrog rau theem ntawm CKD. Cov kev sib raug zoo ntawm tus kheej biomarkers yog me me (qhov loj tshaj kev sib raug zoo R2=0.14 yog nruab nrab ntawm eGFR thiab protein), qhia tias txhua tus biomarkers yog muab cov ntaub ntawv ywj pheej rau kev kwv yees ntawm lub raum raug mob. Tus Thawj Saib Xyuas Kev Tshawb Fawb (PCA) (Daim duab 2B) qhia txog kev sib raug zoo ntawm kev ywj pheej ntawm kev sib txuas ntawm biomarkers rau tag nrho cov kev hloov pauv hauv kev ntsuas ntsuas thiab qhia txog qhov tseem ceeb ntawm kev koom tes ntawm m-cfDNA, cf-DNA, thiab CXCL10 raws li muab tus nqi ywj pheej hauv tiam ntawm Composite KIT Score. Clusterin yog tib lub raum raug mob biomarker uas tsis tseem ceeb hauv kev txheeb xyuas ntau yam (p-value=0.1671). Cov xwm txheej no tseem ceeb tias, txawm hais tias luam tawm cov ntaub ntawv ntawm kev sib raug zoo ntawm cov ntshav cfDNA ntau thiab lub raum tsis ua haujlwm [27,28], tso zis cfDNA hauv cov chaw no yuav tsis txaus ib leeg, thiab muaj txiaj ntsig suav nrog ntau yam biomarkers los tsim cov qhab nia KIT sib xyaw rau CKD kev soj ntsuam.

Table 4. Multivariate logistic regression of kidney injury status as assessed by individual KIT urine biomarkers.

CXCL10 is a key inflammatory cytokine dysregulated in immune-mediated renal injury [45–51]. To evaluate where CXCL10 identifies a specific cause of CKD, such as immune-mediated causes of renal injury from systemic lupus erythematosus, rheumatoid arthritis, antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, we evaluated which CKD categories had a high abundance of urinary CXCL10. Interestingly, only ~30% of the immune-mediated cohort had very high CXCL10 values (>100 pg / mL), tab sis, nyob rau hauv ntau qhov kev tiv thaiv kab mob rau lub raum kev raug mob, cov txiaj ntsig no tsawg thiab tuaj yeem cuam tshuam txog kev tiv thaiv kab mob lossis kev tiv thaiv kab mob. Ua rau peb xav tsis thoob, ~ 30 feem pua ​​​​ntawm cov neeg mob ntshav siab thiab mob ntshav qab zib mellitus kuj muaj qhov tso zis siab CXCL10, yam tsis muaj kev txheeb xyuas cov kab mob tiv thaiv kab mob. Tsis muaj kev sib koom ua ke ntawm cov zis CXCL10 thiab theem CKD.

Figure 2C displays the KIT Score, shown here as a function of CKD stage (based on the eGFR) and matched with presence (red dots) or absence (black dots) of proteinuria (threshold cut of urine protein/creatinine ratio of >0.2). The healthy controls are marked in green and are shown in a pre-CKD 1 or CKD 0 stage where the eGFR is >90 mL / min / 1.73 m2 zoo li hauv CKD 1, tsis muaj proteinuria lossis qhia tias muaj kev pheej hmoo rau lub raum raug mob. Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias ~ 15 feem pua ​​​​ntawm cov kev tswj hwm kev noj qab haus huv tau sim ntawm no muaj qhov siab me me hauv lawv cov KIT Score (tsuas yog siab dua qhov kev pheej hmoo siab ntawm 18.5). Nyob rau theem ntawm txoj kev tshawb no, peb tsis tuaj yeem txheeb xyuas seb cov kev tswj kev noj qab haus huv no nrog KIT Cov qhab nia siab dua puas muaj kev pheej hmoo rau lub raum raug mob, vim tias txhua yam kev kawm tau raug txheeb xyuas.

Table 5 qhia txog kev sib cais ntawm cov qhab nia nruab nrab ntawm KIT los ntawm CKD theem thiab rau cov neeg tuaj yeem noj qab haus huv, thiab peb nco txog qhov tseem ceeb ntawm kev nce KIT Score los ntawm kev nce qib CKD. KIT Score tuaj yeem paub qhov txawv ntawm CKD 1 thiab 2 (28.9; 95 feem pua ​​​​CI: 27.9, 29.9) los ntawm cov neeg ua haujlwm noj qab haus huv tsis muaj CKD (11.0; 95% CI: 9.5, 12.6); p-value < 0="" 00001).="" thaum="" muab="" piv="" rau="" kev="" tswj="" hwm="" kev="" noj="" qab="" haus="" huv,="" muaj="" kev="" sib="" koom="" ua="" ke="" ntawm="" kit="" score="" thiab="" predisposition="" rau="" lub="" raum="" raug="" mob,="" txawm="" tias="" nyob="" rau="" hauv="" cov="" kev="" kawm="" uas="" muaj="" lub="" raum="" ua="" haujlwm="" hauv="" ckd="" 1="" (egfr=""> 90), nrog rau qhov zoo sib xws ntawm x=148.4 (LR p-tus nqi <0.0001) thiab="" qhov="" ntsuas="" qhov="" ntsuas="" ntawm="" 18.5="" muaj="" qhov="" rhiab="" heev="" thiab="" qhov="" tshwj="" xeeb="" ntawm="" 92.9="" (txhua="" 95="" feem="" pua="" ​​​​ci:="" 87.0="" feem="" pua,="" 96.7="" feem="" pua)="" thiab="" 94.4="" feem="" pua="" ​​(txog="" 95="" feem="" pua="" ​​​​6.8,="" 84="" feem="" pua),="" feem="" cov="" txiaj="" ntsig="" zoo="" ib="" yam="" no="" tau="" nthuav="" dav="" ntxiv="" rau="" kit="" qhov="" kev="" ntsuam="" xyuas="" muaj="" peev="" xwm="" txheeb="" xyuas="" ob="" qho="" tib="" si="" ckd="" 1="" thiab="" 2,="" nrog="" rau="" qhov="" muaj="" feem="" cuam="" tshuam="" x="196.5" (lr="" p-value="">< 0.0001),="" nrog="">

the >18.5 KIT Score threshold having a sensitivity of 95.8% (exact 95% CI: 92.2, 98.1%) for early CKD detection. A total of 60% of patients in CKD 1 have elevated KIT Scores >18.5, txawm tias lawv muaj lub raum ua haujlwm "ib txwm" thiab tsis muaj proteinuria. Cov no yog cov neeg mob lub hom phiaj uas peb xav ntes nrog KIT kev soj ntsuam raws li lawv cov theem pib CKD yuav tsis raug kuaj pom los ntawm cov qauv kev kuaj xyuas tam sim no. Qhov tseeb, KIT Score qhia txog 92 feem pua ​​​​ntawm cov neeg mob hauv CKD 1 uas tsis muaj proteinuria vim muaj mob raum thaum ntxov. Hauv CKD 2–3, txawm hais tias kwv yees li 60 feem pua ​​​​ntawm cov neeg mob tsis muaj proteinuria, KIT Score pom tag nrho cov neeg mob uas muaj kev pheej hmoo siab thiab muab ntau qhov sib txawv rau txhua tus neeg mob CKD raug mob lub nra. Hauv CKD 4–5, proteinuria thiab KIT Scores yog qhov sib txuam ntau dua vim tias lub raum puas tsuaj tau nce siab thiab proteinuria tau lees paub tias yog tus cim lig ntawm lub raum raug mob.

Table 5. Distribution of mean KIT Scores and presence/absence of proteinuria by CKD stage.

Yog li, cov txiaj ntsig sib koom ua ke no qhia tau meej meej tias qhov kev ntsuam xyuas ua tiav nws lub hom phiaj tseem ceeb thiab theem nrab ntawm kev kwv yees lub raum raug mob nrog kev nkag siab ntau dua li cov qauv kev kuaj mob tam sim no (eGFR, SCr, proteinuria), thiab, tsis zoo li peb qhov kev soj ntsuam tam sim no, KIT Score tuaj yeem txheeb xyuas cov theem ntxov heev ntawm CKD hauv cov tshuaj ntsuam pej xeem.

4. Kev sib tham

Kev tsav tsheb tom qab kev txhim kho ntawm KIT kev soj ntsuam thiab KIT Score yog qhov kev lees paub ntawm qhov loj, thiab nce, lub nra ntawm lub raum tsis lees paub kev raug mob [52], sib xyaw ua ke los ntawm qhov tsis muaj zog ntawm cov qauv kev saib xyuas tam sim no [53] hauv kev nthuav tawm tiag thiab "pob" lub nra ntawm lub raum kab mob. Kev taug qab lub raum kev puas tsuaj rau tib neeg los ntawm kev kuaj zis ib txwm yog lub hom phiaj uas xav tau, vim tias cov teeb liab lom neeg los ntawm cov zis tuaj yeem muab lub qhov rais qhia txog kev noj qab haus huv ntawm lub raum. Txawm li cas los xij, kev kuaj zis los kwv yees kev raug mob rau lub raum, tsis hais txog qhov tshwm sim, tseem yog qhov kev xav tau ntawm kev kho mob thiab kev sim biochemistry kom ua tiav, vim muaj ntau yam cuam tshuam hauv cov zis xws li proteases [54,55], ua rau biomarker degradation thiab Kev sib txawv ntawm cov neeg sib txawv hauv cov zis pH-tag nrho cov uas tuaj yeem cuam tshuam kev txhim kho ntawm qhov kev kuaj xyuas muaj zog. Targeted proteomic studies [56–59], fueled by protocolized urine sampling from prospective clinical trials, spanning a decades (hauv peb lub chaw soj nstuam ntawm Stanford University thiab UCSF), tau coj mus rau kev txhim kho cov txheej txheem kev khiav hauj lwm (SOPs) rau kev sau zis, stabilization. , kev ua haujlwm, kev soj ntsuam ntawm cov khoom cuam tshuam, khaws cia thiab thauj los ntawm qhov chaw nyob deb mus rau qhov chaw ua haujlwm hauv nruab nrab [60]. Tsis tas li ntawd, ntau tshaj kaum xyoo ntawm kev hloov pauv thiab LC-MS / MS-raws li kev tshawb fawb txog zis proteomic [48,50,58,61–64] tau ua rau muaj kev nkag siab tob tob txog kev mob raum nyob rau ntau qhov laj thawj ntawm CKD, uas ua rau kev xaiv. ntawm biomarkers rau kev suav nrog hauv KIT kev soj ntsuam los sawv cev kev raug mob thoob plaws hauv lub raum sib txawv.

Qhov kev tshawb fawb no tau coj peb mus rau 6 tus cim biomarkers: cDNA, methylated cfDNA, clusterin, CXCL10, creatinine, thiab urinary protein. Cell-dawb DNA tau raug lees paub tias yog ib qho cim qhia txog kab mob hnyav hauv cov ntshav ntawm cov neeg mob uas muaj kab mob autoimmune [65,66] thiab qog [67]. Txawm li cas los xij, lawv qhov kev siv hluav taws xob hauv plasma yog txwv rau qhov teeb tsa ntawm ntau yam kab mob thiab kab mob, vim tias tag nrho cfDNA lub nra yuav cuam tshuam cov txheej txheem sib xyaw ntawm ntau yam kab mob, thaum lub cev lossis qhov chaw tshwj xeeb ntawm tes tsis muaj DNA ntsuas hauv plasma yuav tsum tau siv cov thev naus laus zis sib txuas thiab. bioinformatics [68,69]. Txawm li cas los xij, vim tias cfDNA hauv cov zis tshwj xeeb cuam tshuam txog kev koom tes ntawm lub raum, KIT cfDNA kev soj ntsuam ua rau muaj kev nkag siab zoo heev ntawm lub raum raug mob los ntawm qhov pheej yig ELISA-based assay. Kev ntsuas ntawm methylated fragments ntawm cfDNA muab qhov tshwj xeeb ntxiv txog hom kev raug mob. Thaum lub ntiaj teb hypermethylation tau cuam tshuam nrog kev tiv thaiv lub raum raug mob thiab nce fibrosis, lub ntiaj teb hypomethylation yog txuam nrog kev laus ntawm lub raum poob thiab lub raum ischemia-reperfusion raug mob [31,32,70]. Raws li nrog peb qhov laj thawj hauv kev ntsuas ntawm cfDNA, peb pom tias kev hloov pauv thoob ntiaj teb hauv lub xeev methylation ntawm cfDNA ua rau muaj kev ntxub ntxaug ntawm cov kab mob hauv lub raum yam tsis tas yuav tsum muaj qhov tshwj xeeb ntawm loci-specific sequencing lossis PCR.

CXCL10 tau tsim tau zoo los ua tus cim ntawm kev tiv thaiv kab mob hauv ntau lub ntsiab lus vim nws lub luag haujlwm ua ligand rau CXCR3 receptor [33,34,37,45,51,71]. Peb yav dhau los tau qhia tias CXCL10 thiab cfDNA, raws li kev ntsuas los ntawm KIT kev soj ntsuam, tuaj yeem kuaj pom lub ntsws ntev allograft tsis ua haujlwm hauv lub ntsws hloov pauv nrog rau kev tsis lees paub hauv lub raum hloov pauv [35,72,73]. Strikingly, dab tsi peb pom nyob rau hauv txoj kev tshawb no yog hais tias muaj ib tug tseem ceeb tus naj npawb ntawm cov neeg mob uas ib txwm tsis muaj zog lub raum kab mob, xws li kub siab thiab hom 2 mob ntshav qab zib, uas tau nce CXCL10, muaj peev xwm qhia tau hais tias ib tug dav dav siv nyob rau hauv kev tshawb nrhiav ntawm ntxov- theem raum raug mob. Cov kev tshawb fawb ua ntej tau txheeb xyuas hom 2 mob ntshav qab zib mellitus kom muaj qhov tseem ceeb CXCL10-cov khoom nruab nrab [74] thiab tau txheeb xyuas cov kab mob endothelial cell-produced CXCL10 ua ib qho tseem ceeb rau kev kub siab [75]. Peb cov kev tshawb fawb pom tau tias CXCL10 tuaj yeem txheeb xyuas tsis yog cov neeg mob uas muaj lub raum tsis muaj zog tiv thaiv kab mob nkaus xwb tab sis kuj muaj lwm yam ua rau, cov uas nyiam tuaj yeem tshwm sim tsis zoo nrog cov tsos mob lig ntsig txog kab mob.

Cov zis tag nrho cov protein thiab clusterin yog cov cim qhia tau zoo ntawm lub raum tsis ua haujlwm [38,40,41] thiab creatinine zoo-validated nyob rau hauv daim teb raws li ib tug normalizing biomarker [42,43]. Kuj ceeb tias, peb pom tias pawg, tom qab kev txheeb xyuas ntau yam, tsis yog qhov tseem ceeb hauv peb cov qauv ntawm kev raug mob raum hauv cov ntsiab lus ntawm peb lwm cov biomarkers. Qhov no tej zaum yuav yog vim muaj ntau yam ua rau, suav nrog nws cov kev sib raug zoo rau tag nrho cov protein rau creatinine piv, cov khoom uas twb muaj nyob rau hauv cov qauv [38], nrog rau qhov chaw siab variation vim ultradian rhythms ntawm nruj nreem. Kev sib raug zoo ntawm cov ntshav plasma thiab cov zis ntawm pawg neeg [76,77].

Kev tshawb pom ntxov ntawm lub raum raug mob muaj qhov cuam tshuam tseem ceeb hauv kev txwv tsis pub muaj kev nce qib ntawm CKD thiab muaj txiaj ntsig zoo rau kev saib xyuas kev noj qab haus huv thoob ntiaj teb. Raws li kev hloov pauv ntawm lub raum hemodynamic yog qhov ua rau muaj kev cuam tshuam rau lub cev, kev txhim kho kev tswj hwm ntawm lub hauv paus tseem ceeb ntawm CKD yuav tau txais txiaj ntsig tam sim ntawd, tshwj xeeb tshaj yog kev txhim kho thiab nruj tswj ntshav siab [78], kev ruaj ntseg thiab nruj tswj ntawm hyperglycemia [79], thiab Kev tshawb pom ntxov thiab kev tiv thaiv sai rau kev tshem tawm ntawm lub raum mob thiab raug mob hauv cov kab mob tiv thaiv kab mob xws li kab mob lupus erythematosus [80] thiab mob caj dab rheumatoid [81]. Kev tsis tu ncua thiab kev nce qib ntawm cov qhab nia ntxov tuaj yeem ua rau lub raum ntsuas ntsuas rau obstructive uropathy, nrog kev cuam tshuam sai los tiv thaiv kev mob siab rau hauv lub raum thiab ua rau lub raum cuam tshuam rau lub raum thiab cov tubular tso tawm. Kev kuaj pom ntxov ntawm lub raum raug mob feem ntau yuav tshwm sim hauv qhov chaw saib xyuas thawj zaug, qhov twg muaj kev nkag mus sai, kev ntsuam xyuas yooj yim nrog rau cov txiaj ntsig ntawm lub raum txaus ntshai tau nyeem tawm tuaj yeem ua rau muaj kev xa mus rau nephrologist rau kev tswj ntshav siab, noj zaub mov. Kev hloov kho, kev kho mob ntawm cov kab mob coronary thiab/lossis peripheral vascular kab mob, qhov tshwm sim ntawm CKD thiab kev txiav txim siab ntawm kev kho rau lub raum [82,83]. Lub peev xwm los soj ntsuam ntau qhov kev daws teeb meem ntawm KIT Score dhau lub sijhawm muab lub sijhawm los taug qab kev kho mob raum. Ntxiv nrog rau kev xaiv siv tshuaj lossis kev txhawb nqa kom tswj tau cov kab mob zoo dua, cov tshuaj tiv thaiv tshiab reno, xws li SGLT2 inhibitors thiab lwm tus [84], ntxiv rau qhov tseem ceeb npaum li cas nws tseem ceeb heev kom tuaj yeem kuaj pom kev raug mob raum thaum ntxov, kho. thiab thim rov qab.

Kev ncua ntawm lub raum raug mob thiab yog li kev xa mus rau tus neeg mob yog qhov teeb meem tseem ceeb kom tau txais cov neeg mob tshiab rau hauv cov kev kho mob zoo thaum lawv tseem muaj txoj hauv kev los ua kom muaj txiaj ntsig zoo tshaj plaws ntawm kev kho lub raum. Txhawm rau hais tias muaj pes tsawg tus neeg mob "tsis nco qab" lub sijhawm rau kev kuaj mob CKD nyob rau theem ua ntej ntawm lawv cov kab mob, cov neeg mob nrog ESRD siv lub chaw kho mob xwm txheej ceev ntawm tus nqi rau lub sijhawm siab dua li lub teb chaws tus nqi rau US cov neeg laus - ib nrab ntawm cov uas ua rau nkag mus rau hauv tsev kho mob. [85]. Yog li, ntxiv rau kev siv KIT Score los taug qab lub raum rov qab, muaj txiaj ntsig zoo heev los siv qhov kev ntsuam xyuas no txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhim kho KIT Score trajectory kev nce qib. Kev soj ntsuam tias ib feem peb ntawm cov neeg mob uas muaj CKD etiology vim ntshav siab lossis ntshav qab zib kuj tseem muaj lub cev tiv thaiv kab mob / kab mob kis tau zoo raws li ib feem ntawm lawv lub raum raug mob qhia tias kev txaus siab ntawm kev lom neeg heterogeneity ntawm cov kab mob sib txawv los ntawm tus kheej biomarker qhov tseem ceeb hauv KIT kev soj ntsuam, thiab lwm yam kev tshawb fawb soj ntsuam, yuav tso cai rau ntau txoj hauv kev kho mob rau cov neeg mob CKD.

Cov kev tshawb fawb tsis tu ncua yog npaj thiab tab tom ua nyob rau hauv qhov kev ntsuam xyuas ntawm cov qhab nia ua ntej KIT Score nrog qhov kev ntsuam xyuas ua ntej KIT yuav tso cai rau peb los ntsuas tus nqi ntawm tus kheej biomarkers hauv kev ntsuam xyuas thaum lub raum raug mob thiab lub raum rov qab. Tsis tas li ntawd, peb tab tom teeb tsa kev koom tes nrog cov kws kho mob cov neeg koom tes uas qhov kev ntsuam xyuas ntawm KIT kev soj ntsuam tuaj yeem siv los ua ib txoj hauv kev kom tsis txhob cuam tshuam thiab raug taug qab rau lub raum thaum ntxov raug mob los ntawm kev siv tshuaj nephrotoxicity, muaj nyob rau ntau lub cev tiv thaiv kab mob, xws li calcineurin. inhibitors [86] thiab cov tshuaj tiv thaiv TNF [87]; chemotherapeutic agents xws li cisplatin [88], aminoglycosides [89], thiab tshiab immunotherapies [90], nrog rau raug rau radionuclide contrast media rau kev yees duab [91]. Cov pab pawg ntxiv tau raug sib sau ua ke rau kev tshuaj xyuas qhov twg cov neeg mob tau ua raws li qhov ntev ntawm qhov kev nce qib ntawm CKD, uas yuav ua rau peb nkag siab zoo dua qhov kev sib tw ntawm KIT Score thiab tej zaum yuav pab kho cov theem CKD.

Raws li kev ntsuam xyuas biomarkers tau raug xaiv thiab qhov kev ntsuam xyuas tau tsim nrog lub hom phiaj tshwj xeeb txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau raug mob thaum ntxov, peb kuj tau pom tias KIT qhov kev ntsuam xyuas tuaj yeem tshawb pom tias feem pua ​​​​me me ntawm "ib txwm" tswj tso zis tso zis KIT Cov qhab nia uas hover ntawm qhov siab- kev pheej hmoo ntawm 18.5. Txawm hais tias tsis tau lees paub, nws muaj peev xwm hais tias qhov no tsis yog kev soj ntsuam lub suab nrov thiab cov xwm txheej no yog qhov zoo tiag tiag nrog kev txheeb xyuas ntxov heev ntawm lub raum raug mob nyob rau hauv pre-CKD 1 lossis CKD 0 theem. Raws li 96 feem pua ​​​​ntawm cov neeg uas muaj CKD tsis paub tias lawv muaj [92], ib qho kev sib tw tseem ceeb hauv kev tsim cov qauv kev raug mob raum yog qhov muaj feem ntau uas cov neeg mob tau xaiv los tswj kev noj qab haus huv yeej muaj kab mob raum thaum ntxov. Piv txwv li, tib neeg txoj kev ua neej nyob ntev, coj los ntawm Craig Venter nrog Kev Noj Qab Haus Huv Nucleus kuaj, tau txuas ntxiv thiab ua cov kev ntsuam xyuas ntxiv ntawm cov neeg laus uas tsis muaj tsos mob thiab pom muaj kev sib raug zoo ntawm cov kab mob hauv 21 feem pua ​​​​ntawm lawv cov "kev noj qab haus huv" cov neeg koom nrog suav nrog urologic. / kab mob raum, qhia tias xav tau kev tshuaj ntsuam xyuas ntxiv. Qhov no yog qhov tseeb tshwj xeeb ntawm cov kab mob uas qhov kev cuam tshuam ntxov tuaj yeem ncua lossis txawm tias tus kab mob rov qab mus. Peb pom CKD thiab lub raum raug mob tag nrho los ua tus qauv kab mob uas qhov no yog qhov tseeb, vim ntau txoj kev ua neej thiab kev kho mob tuaj yeem tiv thaiv kev mob raum tsis zoo ntxiv [6,82,83,92].

Ib qho kev txwv ntawm kev tsim kev kawm tam sim no yog kev siv cov pej xeem ntxiv rau cov kev kawm CKD los ntawm qhov chaw zov me nyuam tertiary. Cov ntsiab lus tau txais los ntawm kev tshuaj xyuas ntau dua thiab cov chaw hauv zej zog tuaj yeem yog tus neeg sawv cev ntawm cov pej xeem, tshwj xeeb tshaj yog rau kev kuaj pom ntawm CKD thaum ntxov. Tsis tas li ntawd, qhov kev tshawb fawb no yog hla ntu thiab tej zaum yuav tsis muaj tag nrho cov sawv cev ntawm CKD thaum ntxov thiab lig. Cov kev tshawb fawb ntev soj ntsuam cov neeg mob uas muaj cov tsos mob ntawm CKD thaum ntxov yog npaj rau kev txhim kho kev soj ntsuam ntawm qhov kev tshawb pom ntxov ntawm KIT Score thiab rau qhov cuam tshuam ntawm kev tshawb pom ntxov ntawm CKD kev nce qib. Thaum kawg, nws tuaj yeem ua tau ntxiv rau KIT Score nrog ntxiv biomarkers kom tso cai txhim kho kev kuaj mob ntawm CKD thiab txo qis qhov xav tau rau kev ntsuas ntshav creatinine thiab proteinuria.

Qhov txiaj ntsig zoo ntawm kev lag luam ntawm kev tshawb pom lub raum raug mob thaum ntxov thiab nws txoj kev kho mob tsis tuaj yeem raug lees paub. Yuav luag ib feem peb ntawm Medicare cov peev nyiaj tau mob siab rau kev tswj hwm kev raug mob raum thiab kab mob hauv Asmeskas. Qhov poob ntawm lub raum ua haujlwm hauv CKD 5 ntxiv ib qho nyiaj txiag ntxiv ntawm ~ $ 80,000 ib xyoos vim yog kev pab cuam lim ntshav. Txawm hais tias kev hloov lub raum tso cai rau cov neeg mob tuaj yeem lim ntshav, qhov tsis txaus ntawm lub raum pub dawb, ob qho tib si nyob thiab cadaveric, hloov lub raum, nrog tus nqi pib pib ntawm ~ $ 100,000, ua raws li cov nqi kho mob ntawm ~ $ 20,{{ 6}}/xyoo, tsuas yog ib qho me me nyob rau hauv cov nyiaj dialysis Medicare [93]. Txoj hauv kev rau cov naj npawb ntawm cov neeg mob nrog CKD yuav tsum tau nce ntxiv mus thoob ntiaj teb, nrog rau kev rog ntau dua, ua rau cov neeg muaj ntshav siab thiab ntshav qab zib nce ntxiv [94]. Tsis tas li ntawd, kev hloov pauv ntawm haiv neeg hauv cov kab mob raum ua rau muaj teeb meem kev noj qab haus huv hauv tebchaws, yuav tsum tau kuaj xyuas pej xeem nrog raum biopsies rau kev tshawb pom ntxov ntawm lub raum raug mob los ntawm IgA raum kab mob hauv South-East Asia [95], qhov twg IgA raum kab mob yog thawj qhov ua rau lub raum tsis ua haujlwm. . Kev suav nrog qhov kev ntsuam xyuas tsis muaj kev cuam tshuam rau lub raum raug mob, los hloov cov txheej txheem invasive, tus nqi siab, kev mob qog noj ntshav siab, yuav ua rau muaj txiaj ntsig loj rau kev noj qab haus huv rau cov neeg muaj kev pheej hmoo.

Cistanche can relieve kidney disease

Cistanche tubulosa tiv thaiv kab mob raum thiab raug mob, nyem qhov no kom tau txais cov qauv


Hauv kev xaus, qhov kev tshawb fawb no muab cov qauv qhia rau KIT assay biomarkers, KIT assay algorithm txoj kev txhim kho, KIT Score txhais thiab nws qhov kev ua tau zoo rau kev tshawb pom ntxov ntawm lub raum raug mob, thiab nws qhov sib piv ncaj qha nrog cov qauv kev kuaj xyuas tam sim no. Txoj kev tshawb no qhia tias kev kuaj KIT tuaj yeem siv tau (1) raws li kev tshuaj ntsuam xyuas thaum muaj kev txhawj xeeb ntawm cov kab mob sib kis uas paub tias yuav ua rau muaj kev pheej hmoo ntawm CKD, xws li mob plawv, rog, ntshav qab zib, yam tsis muaj ntaub ntawv ntawm lub raum txawv txav. ua haujlwm los ntawm kev ntsuas tam sim no; (2) raws li kev soj ntsuam ntxiv los saib xyuas lub nra thiab qhov ua tiav ntawm CKD hauv cov neeg mob uas tam sim no tus qauv ntawm kev saib xyuas twb tau kuaj pom kev raug mob raum, piv txwv li, cov neeg mob uas paub txog CKD ua ntej ntawm ntau theem ntawm cov kab mob hauv lub raum; (3) tso cai rau kev soj ntsuam rhiab heev ntawm kev rov qab los ntawm lub raum raug mob thaum raug rau cov kev kho mob sib txawv reno-tiv thaiv thiab kev xaiv tswj. Cov kev tshawb fawb ntxiv yog xav tau, thiab npaj, rau kev soj ntsuam ntev ntawm cov neeg mob nyob rau lub sijhawm kom nkag siab zoo txog keeb kwm ntawm kev loj hlob ntawm CKD, cov txiaj ntsig ntawm kev tshawb pom ntxov, kev cuam tshuam, thiab kev saib xyuas, thiab cov ntsiab lus kis kab mob uas CKD raug mob yuav raug kho thiab nce zuj zus. .


Tus sau kev koom tes:MMS, JYCY, DW, thiab TKS tsim kev kawm thiab kev sim; JML, ID, VL, SS, DL, KS, RS, AC, PCL, thiab ML, ua cov kev sim; DW, JYCY, RDS, thiab MMS txheeb xyuas cov ntaub ntawv; DW, JYCY, thiab MMS ua cov duab; JYCY, DW, RDS, TKS, thiab MMS tau tsim thiab kho cov ntawv; Txhua tus kws sau ntawv tau hloov kho cov ntawv sau tseem ceeb rau cov ntsiab lus tseem ceeb ntawm kev txawj ntse thiab pom zoo rau qhov kawg ntawm cov ntawv sau. MMS tau nkag mus rau tag nrho cov ntaub ntawv hauv txoj kev tshawb fawb thiab ua lub luag haujlwm rau kev ncaj ncees ntawm cov ntaub ntawv thiab qhov tseeb ntawm cov ntaub ntawv tsom xam.

Nyiaj txiag:MMS thiab TKS muaj kev tshawb fawb los ntawm NIH (NIAID thiab NIDDK). Cov peev nyiaj tsis muaj lub luag haujlwm hauv kev tsim qauv, sau cov ntaub ntawv, kev tshuaj xyuas, kev txiav txim siab tshaj tawm, lossis npaj cov ntawv sau.

Kev lees paub:Peb ua tsaug rau kev pab los ntawm cov kws kho mob, cov kws kho mob, cov neeg ua haujlwm tshawb fawb, cov neeg mob, thiab tsev neeg cov neeg mob.

Kev tsis sib haum xeeb ntawm kev txaus siab:MMS, DW, thiab JYCY yog tus tsim ntawm KIT Bio, Inc. (Los Altos, CA, USA), IP uas yog tus tswv tshwj xeeb los ntawm Regents, University of California San Francisco thiab tau tso cai rau KIT Bio. Tag nrho lwm tus kws sau ntawv tshaj tawm tsis muaj kev cuam tshuam ntawm kev txaus siab

1. KIT Bio, 665 3rd Street, San Francisco, CA 94107, USA; drew@kit.bio (DW); joshua.yang@ucsf.edu (JYCY)

2. Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA;

reuben.sarwal@ucsf.edu (RDS); tara.sigdel@ucsf.edu (TKS); juliane.liberto@ucsf.edu (JML);

izabella.damm@ucsfmedctr.org (ID); victorialouie11@gmail.com (VL); shristisigdel@gmail.com (SS); peichen@berkeley.edu (P.-CL)

3. Masters in Translational Medicine Program, University of California Berkeley, Berkeley, CA 94720, USA; devonlivingstone@berkeley.edu (DL); katherine_soh@berkeley.edu (KS); archakra@berkeley.edu (AC); liangmichael@berkeley.edu (ML)

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