Biomarkers Ntawm Kab Mob Raum Hauv Nees: Kev Ntsuam Xyuas Ntawm Cov Ntaub Ntawv Tam Sim No Ⅱ

3. Cov txiaj ntsig

3.1. Cov txiaj ntsig ntawm Kev Tshawb Fawb Kev Tshawb Fawb

Los ntawm Kev Tshawb Nrhiav Pubmed, 18 cov kev tshawb fawb tau txheeb xyuas kom suav nrog hauv qhov kev tshuaj xyuas no (Daim duab1). 

Daim duab 1. Flow daim duab ntawm cov ntaub ntawv tshawb fawb txog kev tshawb fawb txog biomarkers ntawm equinekab mob raum. SDMA-symmetric dimethylarginine; NGAL-neutrophil gelatinase-associated lipocalin. Kev tshawb nrhiav yeej ib txwm ua ke nrog cov lus tshawb nrhiav nees lossis equine.

Cov biomarkers tau txheeb xyuas los ntawm cov ntaub ntawv tshawb fawb suav nrog symmetric dimethylarginine (SDMA; 9 kev tshawb fawb), neutrophil gelatinase-associated lipocalin (NGAL; 5 kev tshawb fawb), cystatin C (3 kev tshawb fawb), podocin (1 txoj kev kawm), MMP (1 txoj kev kawm), N- acetyl-beta-D-glucosaminidase (NAG; 1 txoj kev tshawb fawb).

3.2. Kev paub tam sim no thiab qib ntawm cov pov thawj

3.2.1. Cov cim ntawm lub raum ua haujlwm (Kev kwv yees ntawm GFR) Symmetric Dimethylarginine (SDMA)

Hauv tib neeg thiab tsiaj me, SDMA tau lees paub tias yog qhov muaj txiaj ntsig, txawm tias muaj kev sib cav heev, biomarker rau lub raum ua haujlwm. Nws tau pom tias muaj kev sib raug zoo nrog GFR thiab creatinine thiab nrog kev nce hauv cov ntsiab lus pom ntxov dua li creatinine [12].

Cuaj qhov kev tshawb fawb hauv tag nrho daim ntawv qhia txog SDMA hauv nees (Table 2). Ob peb ntawm cov no suav nrog cov ntaub ntawv ntawm kev txheeb xyuas qhov tseeb ntawm qhov kev sim uas tau siv [13–16]. Tag nrho cov kev soj ntsuam siv tau dhau los ua qhov kev ntsuam xyuas qhov tseeb (theem I ntawm cov txheej txheem validation). Hauv cov kev tshawb fawb sib txawv, cov kev ntsuam xyuas sib txawv tau siv, ntawm qhov kev soj ntsuam muaj muag tau tsim los ntawm IDEXX thiab muaj rau kev siv tshuaj kho mob. Kev khov tsis muaj qhov cuam tshuam tsis zoo rau kev txheeb xyuas SDMA [17].

Ob peb ntawm cov kev tshawb fawb no suav nrog cov ntaub ntawv sib tshooj (phase II). Cov no tau pom cov ntshav qab zib sib txawv ntawm SDMA ntawm (1) cov nees noj qab haus huv piv rau cov nees nrog AKI [18,19], (2) cov nees nrog ntau theem ntawm lub cev qhuav dej [19], thiab (3) cov nees ua siab ntev ua ntej piv rau tom qab kev sib tw, nrog rau kev tshaj tawm -Kev sib tw SDMA ntau dua nrog kev sib tw ntev dua [13]. Tsis muaj qhov sib txawv ntawm cov tshuaj SDMA cov ntsiab lus ntawm cov nees noj qab haus huv piv rau cov nees uas muaj kab mob plawv [14], lossis nruab nrab ntawm cov neeg muaj sia nyob thiab cov neeg tsis muaj sia nyob nrog ntau qib ntawm lub cev qhuav dej (tsawg dua SDMA cov ntsiab lus tau pom nyob rau hauv cov neeg muaj txoj sia nyob dua li cov neeg tsis muaj sia nyob, txawm li cas los xij, qhov no tsis tau txheeb xyuas. sib) [19]. SDMA cov ntsiab lus tsuas yog tau tshaj tawm txog tsawg kawg ntawm equine AKI cov neeg mob (37 kis tau muab faib ua 4 qhov kev tshawb fawb) [15,16,18,19], thiab txog tam sim no tsis tau lees paub equine CKD mob. Ib txoj kev tshawb fawb tsis tau txheeb xyuas qhov sib txawv ntawm SDMA qhov sib txawv ntawm cov nees noj qab haus huv thiab cov nees muaj kev pheej hmoo rau AKI (thiab yog li muaj peev xwm AKI thaum ntxov), qee qhov cim cim (cov zis protein thiab zis protein rau creatinine piv (UP / UC) thiab cov zis GGT / creatinine piv) sib txawv [18]. Ob qhov kev tshawb fawb tau tshaj tawm txog 2 thiab 7 tus neeg mob nrog nce SDMA tab sis ib txwm muaj creatinine; Cov xwm txheej no tau txhais tias muaj peev xwm tseem tsis tau lees paub subclinical AKI lossis CKD mob [15,19]. Yog li ntawd, zoo ib yam li cov tsiaj me, muaj peev xwm ua tau tias SDMA muaj txiaj ntsig zoo los tshawb xyuas cov xwm txheej AKI thaum ntxov thaum creatinine tseem nyob hauv qhov kev siv, tab sis tam sim no tsis muaj pov thawj. Hauv miv thiab dev, SDMA nce hauv cov lus teb rau 40% txo hauv GFR [12]. Tam sim no tsis paub txog cov nees yuav tsum tau poob ntau npaum li cas ua ntej SDMA nce, thiab yog tias nws yog tus cim ua ntej rau AKI dua li creatinine.

Tsis muaj cov kev tshawb fawb equine uas qhia txog qhov zoo tshaj plaws txiav tawm qhov tseem ceeb ntawm SDMA thiab nws qhov rhiab heev thiab tshwj xeeb raws li cov cuab yeej kuaj mob rau AKI lossis CKD hauv nees. Qhov no txhais tau tias tam sim no tsis muaj cov ntaub ntawv ntawm kev kho mob (theem III) ntawm biomarker no ua cov cuab yeej kuaj mob. Raws li kev suav ntawm rhiab heev thiab qhov tshwj xeeb yog raws li kev sib piv ntawm cov qauv kev sim piv rau cov qauv siv tus qauv, nws yuav tsum tau lees paub tias tsis muaj cov qauv siv tau yooj yim thiab txhim khu kev qha.

Tsis tas li ntawd, tsis muaj kev tshawb fawb soj ntsuam kev txhim kho ntawm kev tswj tus neeg mob thaum siv SDMA (theem IV).

Kev siv ntau yam tau txiav txim siab hauv cov kev tshawb fawb nrog tus qauv tsim nyog. Qhov no tau ua rau cov neeg laus thiab cov foals nrog foals uas muaj txiaj ntsig zoo dua li cov neeg laus. Kev siv ntau yam rau cov neeg laus tau tshaj tawm hauv ob chav sib txawv:<14 microgram/dL [15,17,20], or <19 microgr/dL [18], or 0.3–0.8 micromol/L [13,14,16]. Overall, there is a low influence of extrarenal factors on SDMA in adults, with no differences between sex [15–17,21], age in adults [15–17], body weight [15,16], or body condition score [15]. Small breed differences have been noted but did not affect the cutoff values [15]. Donkeys have similar reference values as horses [17]. Foals have significantly higher values [16,20,21], ranging up to 100 microgr/dL at birth (with an upper limit of the assay of 100 microgr/dL) [20] or up to 168 microgr/dL for the first 36H [21]. SDMA concentrations decrease in the first month of life to <24 microgr/dL [20], but 2 to 6-month-old foals have been reported to still have higher SDMA concentrations than adults (1.5 ± 0.4 micromol/L) [16]. Similar to SDMA in other species, factors that impact GFR also influence SDMA [12]. This has been confirmed by elevated SDMA in dehydrated horses [19] and in exercising endurance horses [13].

NYEEM NTXIV NTAWM NO TUAJ RAU HAUV TSEV KAWM NTAWV CISTANCHE FOR KIDNEY DISEASE REATMENTS

Hauv kev xaus, tam sim no tsis muaj pov thawj rau kev kho mob ntawm SDMA txhawm rau txhawm rau kuaj mob raum hauv cov nees tau piav qhia los ntawm qhov tseeb tias tam sim no tsuas muaj qee qhov kev tshawb fawb thiab txwv cov ntaub ntawv ntawm cov kab mob raum muaj nyob rau hauv cov ntaub ntawv, tsis muaj cov ntsiab lus txiav tawm thiab rhiab heev. / tshwj xeeb rau kab mob raum muaj. Tsis tas li ntawd, qhov kev txhawj xeeb tseem ceeb yog qhov tsis muaj pov thawj rau SDMA kom raug thiab raug ntes cov nees nrog AKI ua ntej tshaj creatinine. Raws li cov ntaub ntawv muaj, cov kws sau ntawv ntseeg tias SDMA tej zaum yuav muaj qee lub peev xwm ua biomarker rau kab mob raum hauv nees (xws li tej zaum kuaj pom kab mob hauv lub raum ua ntej creatinine). Txawm li cas los xij, nyob rau theem no, muaj cov ntaub ntawv tshawb fawb tau txwv hauv kev txhawb nqa rau SDMA siv los ua tus qauv biomarker rau txhua tus kab mob raum. Txawm li cas los xij, txij li cov kev ntsuam xyuas SDMA muaj kev lag luam rau kev siv tshuaj kho mob, thiab cov txiaj ntsig tau tsim muaj txiaj ntsig zoo muaj, hauv cov kev xaiv uas xav tias muaj kab mob raum ntxov lossis tsis yog azotemic thiab nrog kev txiav txim siab, kev ntsuas SDMA tuaj yeem txiav txim siab.

Cystatin C

Hauv tib neeg cov tshuaj, cystatin C yog ib qho kev tshawb xyuas lub raum biomarker zoo uas sib raug zoo nrog GFR piv rau cov ntshav creatinine [22]. Xws li, Cystatin C tuaj yeem muab qhov zoo hauv kev kuaj mob raum hauv cov xwm txheej uas creatinine tsis ua haujlwm [22]. Txawm li cas los xij, kev tshawb fawb tsis ntev los no hauv cov dev piv rau SDMA, creatinine thiab Cystatin C nrog GFR kwv yees los ntawm scintigraphy thiab pom tias cystatin C tsis zoo rau SDMA thiab creatinine hauv kev kwv yees GFR [23].

Tsuas muaj 3 cov ntawv tshaj tawm uas qhia txog kev ntsuas cystatin C hauv cov nees (Table 3). Hais txog kev kuaj xyuas qhov tseeb (theem I), ib qho kev tshaj tawm siv tib neeg cov tshuaj tiv thaiv kab mob latex tab sis yuav tsum txiav txim siab tias qhov kev ntsuam xyuas tsis ua haujlwm rau cov qauv equine [24]. Ob qhov kev tshaj tawm ntxiv, ob qho tib si siv cov khoom siv ELISA muag (MyBioSource, San Diego, CA, USA, tus lej xov tooj MBS022947) [25,26]. Cov khoom siv no tau lees paub los ntawm cov chaw tsim khoom siv rau kev siv cov ntshav thiab cov zis kuaj ntawm equine keeb kwm, tab sis tsis muaj ntaub ntawv ntawm qhov kev lees paub no muaj nyob hauv cov ntaub ntawv. Tam sim no tsis muaj lub chaw soj nstuam lag luam uas muab kev kuaj cystatin C rau kev kho mob.

Ob qhov kev tshawb fawb tau tshaj tawm cov ntaub ntawv sib tshooj (phase II). Cov zis thiab cov ntshav cystatin C ntau dua tau tshaj tawm tias muaj ntau dua hauv cov nees nrog AKI piv rau cov nees noj qab haus huv tsis muaj AKI [25]. Nees uas tau txiav txim siab tias yuav muaj kev pheej hmoo rau AKI (nrog colic tab sis tsis muaj endotoxemia, sepsis lossis kab mob inflammatory teb, thiab tsis muaj azotemia) tau pom tias muaj ntshav siab thiab zis cystatin C concentrations [25]. Qhov no qhia tias cystatin C muaj peev xwm kuaj tau AKI thaum ntxov ua ntej cov ntshav creatinine ntau ntxiv. Hauv lwm txoj kev tshawb fawb, cov ntshav cystatin C ntau dua hauv cov nees uas muaj tus kab mob Theileria equi. Qhov kev nce ntxiv hauv cystatin C tau pom tias tsis muaj kev kho mob cuam tshuam nrog azotemia thiab cuam tshuam rau qib ntawm cov kab mob parasitemia [26].

Siwinska et al. qhia txog kev kho mob ntawm cystatin C nrog kev txiav txim siab ntawm qhov pom kev txiav tawm qhov tseem ceeb thiab lawv qhov rhiab heev thiab tshwj xeeb rau kev kuaj mob AKI (Phase III) [25]. Qhov zoo tshaj plaws txiav tawm tus nqi rau serum cystatin C yog 0.53 mg/L nrog rau qhov rhiab heev thiab tshwj xeeb ntawm 0.64 thiab 0.85; rau urinary cystatin C qhov no yog ntawm 0.20 mg/L nrog rau qhov rhiab heev thiab qhov tshwj xeeb ntawm 0.82 thiab 0.85 [25]. Cov ntshav cystatin C concentrations hauv cov lus hais saum toj no Theileria equi tus kab mob nees qhia los ntawm Ahmadpour li al. [26] tau meej meej siab dua qhov kev txiav txim siab zoo tshaj plaws los txheeb xyuas AKI teev los ntawm Siwinska li al. [25]. Qhov kev soj ntsuam no kuj txhawb lub tswv yim tias cystatin C muaj peev xwm kuaj pom AKI thaum ntxov thaum tsis muaj azotemia. Serum cystatin C tau zoo dua rau kev txiav txim siab AKI (yog li txhawm rau txheeb xyuas cov nees noj qab haus huv) ntau dua li kev lees paub AKI, qhov urinary cystatin C tau zoo sib npaug hauv kev txiav txim lossis txiav tawm [25].

Tam sim no tsis muaj cov ntaub ntawv muaj nyob rau theem IV rau cystatin C hauv nees.

Cov txiaj ntsig ntawm cov ntshav cystatin C concentrations los ntawm cov nees noj qab haus huv tau tshaj tawm tias yog {{0}}.13–0.71 mg/L [25] thiab 0.11 ± {{ 10}}.07 ng/mL [26], thiab tso zis ntau 0.06–0.50 mg/L [25]. Txawm li cas los xij, cov txiaj ntsig no yog nyob ntawm cov nees me me, thiab tam sim no, tsis muaj kev tshawb fawb tau ua los tsim kom muaj cov ntaub ntawv siv tau zoo. Tsis tas li ntawd, tsis muaj cov ntaub ntawv muaj nyob hauv foals.

Tsis muaj kev tshawb fawb tau kawm tias cystatin C cuam tshuam li cas los ntawm cov xwm txheej ntxiv hauv cov nees, tab sis cystatin C tau tshaj tawm hauv tib neeg kev tshawb fawb tsis yog nyob ntawm lawv [22].

Hauv kev xaus, tam sim no tsis muaj pov thawj rau kev siv tshuaj kho mob cystatin C txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm cov kev tshawb fawb ntawm CKD muaj nyob rau hauv cov ntaub ntawv. Raws li cov ntaub ntawv muaj, cov kws sau ntawv ntseeg tias cystatin C tuaj yeem tuav lub peev xwm ua biomarker rau cov kab mob raum (xws li kev kuaj pom kab mob raum ua ntej piv nrog creatinine) thiab yuav tsum tau suav nrog hauv kev tshawb fawb yav tom ntej. Txawm li cas los xij, nyob rau theem no, cov ntaub ntawv tshawb fawb muaj tsawg dhau los txhawb kev kho mob siv cov biomarker no. Tsis tas li ntawd, tam sim no tsis muaj kev ntsuam xyuas muaj rau kev kho mob, uas ntxiv txwv nws txoj hauv kev rau kev siv tshuaj kho mob ntawm lub sijhawm no.

3.2.2. Cov cim ntawm kev puas tsuaj: Glomerular puas tsuaj Podocin

Podocin yog ib qho transmembrane signaling protein tshwj xeeb tshaj yog nyob rau hauv podocytes (tseem ceeb glomerular epithelial hlwb) thiab tso tawm nyob rau hauv cov zis tom qab podocyte puas [27]. Cov ntawv ceeb toom hauv tib neeg thiab tsiaj txhu qhia tias kev paub ntxov ntxov ntawm kev tso zis ntau ntxiv ntawm podocytes tuaj yeem pab txhawb kev kuaj mob raum [28,29]. Tsis tas li ntawd, podocyturia muaj feem cuam tshuam nrog kev txhim kho ntawm glomerupathies [30,31]. Tsuas muaj 1 txoj kev tshawb fawb uas qhia txog kev ntsuas podocin hauv nees (Table 4). Re garding qhov kev xeem validation (theem I), nyob rau hauv cov ntaub ntawv tshaj tawm podocin tau kuaj pom nyob rau hauv cov zis siv ib tug validated qualitative txoj kev-kua chromatography-mass spectrometry nyob rau hauv ntau yam tshuaj tiv thaiv hom (LC-MS-MRM) thiab quantitatively siv enzyme-linked immunosorbent assay (ELISA) [27]. Rau qhov kev xeem kom muaj nuj nqis, cov neeg sau ntawv tau siv cov khoom siv ELISA tshwj xeeb uas muaj nyob hauv khw muag khoom (MyBioSource, San Diego, CA, USA, catalog tus lej MBS023791). Cov khoom siv no yog, raws li cov chaw tsim khoom, tuaj yeem siv nrog cov qauv tso zis ntawm equine keeb kwm, tab sis tsis muaj ntaub ntawv ntawm qhov kev lees paub no muaj nyob hauv cov ntaub ntawv. Txoj kev LC-MS-MRM muaj feem yuav muab cov txiaj ntsig zoo dua li ELISA [27]. Tsis muaj lub chaw soj nstuam lag luam uas muab kev kuaj podocin rau kev kho mob. Tib txoj kev tshawb fawb tau tshaj tawm cov ntaub ntawv sib tshooj (phase II) ntawm 71 tus neeg laus cov ntshav sov. Hais txog cov ntaub ntawv zoo (muaj los yog tsis muaj), podocin muaj nyob rau hauv cov zis ntawm tag nrho cov nees nrog AKI thiab ib nrab ntawm cov nees muaj kev pheej hmoo rau AKI (nrog rau colic tab sis tsis muaj endotoxemia, sepsis lossis systemic inflammatory teb syndrome, thiab nrog rau qhov tsis tuaj. azotemia) [27]. Txawm li cas los xij, lub xub ntiag ntawm podocin kuj tau kuaj pom hauv ob peb tus nees noj qab haus huv, zoo ib yam li hauv tib neeg [30]. Yog li ntawd, txawm hais tias muaj podocin nyob rau hauv cov zis hauv nees yog qhov muaj peev xwm qhia txog kev raug mob glomerular nyob rau hauv subclinical thiab kho raum kab mob, qhov ua tau ntawm physiological podocyturia ua rau kev soj ntsuam zoo ntawm podocin kho mob nyuaj siv. Hais txog cov txiaj ntsig ntau, cov zis podocin concentration siab dua hauv cov nees nrog AKI piv rau nees noj qab haus huv [27]. Nees muaj kev pheej hmoo rau AKI tau nce siab podocin concentrations, tab sis tsawg dua nees nrog AKI [27]. Qhov no qhia tau hais tias ntau qhov kev ntsuam xyuas podocin muaj peev xwm ua kom paub meej txog kev raug mob glomerular thiab ntxiv mus, kuaj nws ua ntej cov ntshav creatinine ntau ntxiv. Tib txoj kev tshawb fawb tau tshaj tawm txog kev kho mob ntawm cov zis ntau npaum li cas podocin ELISA los kuaj AKI (Phase III). Qhov zoo tshaj plaws txiav tawm tus nqi yog 0.81 ng / mL nrog rhiab heev thiab tshwj xeeb ntawm 0.73 thiab 0.78 [27]. Lub podocin ELISA tau ua pov thawj tias muaj txiaj ntsig zoo los txiav txim AKI es tsis lees paub AKI [27].

Qhov concentration ntawm cov zis podocin hauv cov nees noj qab haus huv yog 0.19 txog 1.2 ng / mL [27]. Vim muaj tsawg tsawg ntawm cov nees kuaj, tsis muaj qhov tsim nyog siv ntau yam rau podocin concentration. Tsis tas li ntawd, tsis muaj cov ntaub ntawv muaj nyob hauv foals. Txoj kev tshawb fawb muaj tsis tau ntsuas qhov cuam tshuam ntawm cov yam tsis yog lub raum ntawm cov qib podocin hauv cov nees. Kuj tsis muaj cov ntaub ntawv hais txog qhov cuam tshuam ntawm cov xwm txheej no hauv tib neeg. Hauv kev xaus, tam sim no tsis muaj pov thawj rau kev kho mob ntawm cov zis podocin los kuaj cov kab mob hauv lub raum hauv cov nees yog: qhov tsis muaj cov ntaub ntawv txheeb xyuas qhov tseeb, tsis muaj cov ntaub ntawv siv, tsis muaj cov ntaub ntawv hauv foals, tsis muaj kev paub txog kev cuam tshuam ntxiv ntawm podocin concentrations, tsuas yog 1 txoj kev kawm nrog cov ntaub ntawv tsawg muaj nyob rau hauv cov ntaub ntawv, tsis muaj ntaub ntawv ntawm CKD. Raws li cov ntaub ntawv muaj, cov kws sau ntawv ntseeg tias podocin muaj peev xwm ua biomarker rau cov kab mob raum (xws li kuaj pom kab mob raum ua ntej thaum piv nrog creatinine). Txawm li cas los xij, nyob rau theem no, cov ntaub ntawv tshawb fawb muaj tsawg dhau los pab txhawb kev pib kho mob siv cov biomarker no. Ntxiv mus, tam sim no tsis muaj kev sim ua lag luam tam sim no, uas ntxiv txwv nws txoj kev siv ntawm lub sijhawm no.

3.2.3. Cov cim ntawm kev puas tsuaj: Tubular puas Neutrophil Gelatinase-Associated Lipocalin (NGAL)

NGAL yog ib qho me me lipocalin protein synthesized los ntawm activated neutrophils thiab ntau yam epithelial hlwb, nrog rau cov tubular hlwb ntawm lub raum. Qhov nce hauv plasma thiab tso zis ntau ntxiv tshwm sim thaum ntxov li 2 teev tom qab qhov kev thuam ntawm kev thuam [32], thiab muaj feem cuam tshuam rau qib ntawm lub raum puas. NGAL tau pom nyob rau hauv tib neeg thiab tsiaj me los pab tshawb pom ntxov ntawm cov neeg mob uas muaj feem yuav mob los yog mob raum [33–35].

Muaj ob qhov kev ntsuam xyuas hais hauv cov ntaub ntawv equine (Table 5). BioPorto porcine ELISA (Bioporto, Copenhagen, Denmark, cov khoom siv 044) tau raug lees paub rau NGAL ntsuas ntawm equine serum. Los ntawm txhua hom sib txawv tshwj xeeb NGAL ELISA uas muaj kev lag luam los ntawm BioPorto, tsuas yog cov porcine uas txheeb xyuas qhov teeb meem NGAL equine. Equine NGAL tuaj yeem ntseeg tau tias muaj nuj nqis siv cov porcine-specific test thiab cov ntaub ntawv siv tau raug luam tawm [36]. Tom qab qhov tseeb ntawm cov qauv kuaj ntshav, cov khoom lag luam muaj porcine ELISA kuj tau siv los ntsuas NGAL hauv cov kua dej synovial [37] thiab cov kua dej peritoneal [38]. BioPorto ELISA tau siv rau tag nrho tab sis ib qho kev tshaj tawm [25]. Qhov kev tshaj tawm yav dhau los no siv lwm qhov kev lag luam muaj NGAL ELISA xeem tsim los ntawm MyBioSource (San Diego, CA, USA). Qhov ELISA no tau raug lees paub los ntawm cov chaw tsim khoom siv rau cov ntshav thiab cov zis kuaj ntawm equine keeb kwm [25], txawm li cas los xij, tsis muaj cov ntsiab lus muaj nyob hauv cov ntaub ntawv. Cov kws sau ntawv tshaj tawm cov txiaj ntsig zoo sib xws piv nrog lwm cov kev tshawb fawb uas suav nrog cov nees noj qab haus huv thiab cov nees uas muaj kab mob raum [36,38], ntxiv dag zog rau lawv cov ntaub ntawv. Yog li ntawd, qhov kev txheeb xyuas qhov tseeb (Phase I) tau ua tiav rau BioPorto NGAL ELISA, tab sis tso qee qhov khoob rau MyBioSource xeem. Raws li ib sab, cov kev ntsuam xyuas no tsuas yog muaj raws li cov khoom siv ELISA uas muaj cov qauv ntau yuav tsum tau khiav tib lub sij hawm ua qhov kev ntsuam xyuas tsis siv rau qhov chaw kho mob [37]. Tam sim no, tsis muaj chaw soj ntsuam kev lag luam muab NGAL. Tib neeg NGAL tau pom tias muaj kev ruaj khov thiab ntev cia los yog rov ua kom khov-thaw cycles muaj qhov cuam tshuam tsawg heev rau kev ntsuas qhov ntau [37]. Tsis muaj cov ntaub ntawv ntawm qhov no muaj nyob hauv cov qauv ntawm cov nees.

Hais txog kev sib tshooj (Phase II), muaj 2 txoj kev tshawb fawb qhia txog kab mob raum. Piv nrog rau cov nees noj qab nyob zoo cov kev tshawb fawb no qhia tau tias muaj kev nce hauv cov ntshav NGAL hauv cov nees uas tsis muaj kev sib txawv ntawm azotemia [36] lossis hauv cov ntshav thiab zis NGAL concentrations hauv cov nees nrog AKI [25]. Nees uas tau txiav txim siab tias yuav muaj kev pheej hmoo rau AKI (nrog colic tab sis tsis muaj endotoxemia, sepsis lossis kab mob ua rau lub cev tsis muaj zog, thiab tsis muaj azotemia) tau pom tias muaj ntshav siab thiab zis NGAL ntau [25]. Qhov no qhia tias NGAL muaj peev xwm kuaj tau AKI ntxov ua ntej cov ntshav creatinine ntau ntxiv. Tib neeg txoj kev tshawb fawb tau pom tias NGAL tuaj yeem ntes AKI 1-2 hnub ua ntej tshaj li cov txheej txheem ib txwm muaj, tab sis kuj tuaj yeem siv los ua biomarker rau CKD [39]. Lwm cov kev tshawb fawb tsis qhia txog kab mob hauv lub raum, tab sis tsom mus rau qhov uas NGAL kuj ua raws li cov qib protein ntau thiab ua rau muaj kev mob ntxiv; Qhov no tau pom nyob rau hauv cov xwm txheej ntawm equine synovial o thiab kab mob [37] thiab equine colic-txog o [38]. Hauv tib neeg, NGAL kuj tau pom zoo tias yog biomarker rau cov mob uas tsis yog lub raum xws li kab mob, kab mob hauv plab, mob hawb pob, thiab mob hlwb thiab mob qog noj ntshav [39].

Tsuas yog ib qho kev tshawb fawb equine qhia txog kev ua haujlwm kho mob nrog kev txiav txim siab ntawm qhov zoo tshaj plaws txiav tawm qhov tseem ceeb thiab lawv qhov rhiab heev thiab tshwj xeeb rau kev kuaj mob AKI (Phase III) [25]. Qhov zoo tshaj plaws txiav tawm tus nqi rau cov ntshav NGAL yog 95.2 ng / mL nrog qhov rhiab heev ntawm 0.54 thiab qhov tshwj xeeb ntawm 0.93; rau cov zis NGAL qhov no yog ntawm 33.1 ng / mL nrog qhov rhiab heev ntawm 0.64 thiab qhov tshwj xeeb ntawm 0.71 [25]. NGAL tau zoo dua los txheeb xyuas cov nees uas tsis muaj AKI ntau dua li kom paub meej AKI, thiab tsis cuam tshuam nrog cov ntshav creatinine ntau [25]. Cov kws sau ntawv cov kev xav no yog tias qhov tsis muaj kev sib raug zoo nrog cov ntshav creatinine tuaj yeem cuam tshuam nrog qhov sib txawv ntawm cov kab mob pathophysiology (creatinine yog cov cim ua haujlwm thaum NGAL yog tus cim ntawm kev puas tsuaj), lossis los ntawm qhov tseeb tias NGAL kuj nce ntxiv raws li cov lus teb rau kev kho mob [25]. Qhov tseeb tias NGAL kuj nce ntxiv tom qab o, zoo ib yam li lwm hom [34], ua rau nws siv tshuaj kho mob raws li biomarker rau cov kab mob raum nyuaj, tshwj xeeb tshaj yog vim muaj ntau tus neeg mob AKI kuj muaj kab mob hauv lub cev. Nyob rau tib lub sij hawm qhov no ua rau nws nthuav biomarker rau o, nyob rau hauv tsis muaj cov kab mob raum los yog xav tias muaj kab mob raum. Yog li ntawd, nws tau raug pom zoo kom muaj peev xwm ua ib qho kev tshuaj ntsuam xyuas kev noj qab haus huv rau nees, kuaj xyuas qhov mob thiab kab mob raum thaum ntxov [40].

Tam sim no tsis muaj cov ntaub ntawv muaj nyob rau theem IV rau NGAL hauv nees. Sab saum toj siv qhov tseem ceeb ntawm cov ntshav NGAL ntau ntawm cov nees noj qab haus huv tau tshaj tawm txog thaj tsam ntawm 41.9 microg / L [38] txog 103.6 microg / L [36]. Ob txoj kev tshawb fawb nrog cov txiaj ntsig siab dua (95.20 thiab 103.6 microg / L) tsis tau txiav txim siab tawm tsam qhov mob hauv lawv cov pab pawg nees noj qab haus huv [25,36], uas tau ua rau cov kev tshawb fawb nrog cov ntshav NGAL qis (41.9 thiab 47.7 microg / L) [38,40]. Sib nrug los ntawm cov kev tshawb fawb no uas tau tshaj tawm cov ntshav NGAL ntau ntawm cov nees noj qab haus huv tsawg, tsis muaj kev tshawb fawb tseem tau tsim cov txiaj ntsig siv tiag tiag.

Tsis muaj kev tshawb fawb tau tshawb xyuas seb puas muaj lwm yam ntxiv xws li hnub nyoog, poj niam txiv neej, yug me nyuam, lub cev hnyav lossis lub cev tus qhab nia cuam tshuam rau NGAL concentrations. Txawm li cas los xij, muaj ib txoj kev tshawb fawb hauv kev noj qab haus huv Thoroughbred racehorses uas qhia tau hais tias kev tawm dag zog luv luv tsis muaj kev cuam tshuam rau cov ntshav NGAL ntau [40]. Qhov no tsis tuaj yeem raug ntxiv rau txhua hom kev tawm dag zog, thiab tuaj yeem sib txawv rau lub sijhawm ntev zog xws li kev ua siab ntev. Raws li tau hais los saum no, qhov mob ua rau NGAL concentrations [37,38]. Hauv lwm hom, urinary NGAL / creatinine ratio (UNCR) tau siv [41]. Tsis muaj cov ntaub ntawv ntawm qhov piv txwv tam sim no muaj nyob hauv nees.

Muaj ntau qhov kev tshawb fawb ntawm NGAL hauv cov nees uas tau nthuav tawm hauv cov rooj sib tham thiab luam tawm raws li kev sib tham hauv cov ntawv xov xwm sab hauv scientific. Vim tias qhov no tsis yog cov ntaub ntawv uas tau raug tshuaj xyuas thiab tsis tuaj rau hauv Kev Tshawb Fawb Pubmed raws li cov ncauj lus kom ntxaws hauv cov ntaub ntawv thiab cov txheej txheem, cov ntaub ntawv no tsis tau suav nrog hauv kev tshuaj xyuas saum toj no. Txawm li cas los xij, txhawm rau muab cov lus piav qhia luv luv ntawm kev tshawb fawb txuas ntxiv ntawm NGAL hauv cov nees, cov npe luv luv ntawm kev tshaj tawm cov rooj sib tham tau muab hauv qab no ntawm cov ncauj lus tshawb fawb:

- NGAL hauv neonatal foals, ua cov cuab yeej kuaj mob txhawm rau txhawm rau txheeb xyuas qhov sib txawv ntawm azotemia (abstract ECEIM 2020) [42].

- NGAL hauv cov neeg laus nees, overlaps kev ua haujlwm rau lub raum tiv thaiv kev mob (kev paub daws teeb meem ECEIM 2018) [43].

- NGAL hauv cov neeg laus nees, tom qab endotoxemia induction (abstract ECEIM 2018) [43].

- NGAL hauv cov neeg laus nees, ua ib lub cuab yeej los txheeb xyuas cov teeb meem tom qab kev ua haujlwm tom qab castration (abstract ECEIM 2018) [43].

- NGAL hauv cov neeg laus nees, hauv cov kua dej bronchoalveolar (kev paub daws teeb meem ECEIM 2020) [44].

Hauv kev xaus, cov pov thawj tam sim no ploj lawm rau daim ntawv thov kev kho mob ntawm NGAL txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau NGAL Raws li cov ntaub ntawv muaj thiab txiav txim siab tias qhov no yog cov cim cim, cov kws sau ntawv ntseeg tias NGAL muaj peev xwm ua tus biomarker ntxiv rau cov kab mob raum (xws li nws muaj peev xwm kuaj tau AKI ua ntej tshaj creatinine), tab sis kuj muaj peev xwm ua tus cim ntawm qhov mob. Txawm li cas los xij, nyob rau theem no muaj cov ntaub ntawv tshawb fawb tseem txwv los txhawb kev kho mob siv cov biomarker no. Ntxiv mus, tam sim no tsis muaj kev sim ua lag luam tam sim no rau kev kho mob, uas ntxiv txwv nws txoj hauv kev rau kev siv tshuaj kho mob ntawm lub sijhawm no.

Matrix Metalloproteinase 2 thiab 9 (MMP-2 thiab MMP-9)

Metalloproteinases (MMPs) paub txog lawv lub peev xwm los degrade extracellular matrix proteins. Lawv tau raug pom nyob rau hauv tib neeg, thiab kev tshawb fawb tsiaj hauv chaw soj nstuam kom nce qib hauv cov ntshav hauv kev sib raug zoo rau endotoxemia thiab cov zis hauv kev cuam tshuam rau lub raum puas. Cov tom kawg tau pom tias yog qhov nce ua ntej tshaj creatinine [24,45–48]. Tsuas muaj ib txoj kev kawm piav txog MMPs ua rau lub raum biomarkers hauv nees [24] (Table 4). Hauv kev tshaj tawm no los ntawm Arosalo, tsis muaj cov ntaub ntawv txheeb xyuas qhov tseeb (theem I) tau piav qhia. Tus sau hais txog ib txoj hauv kev dhau los los ntsuas MMPs [49], txawm li cas los xij, qhov no tsis yog ib txoj hauv kev tshwj xeeb, nug txog qhov siv tau ntawm cov txiaj ntsig ntawm txoj kev tshawb no. Tam sim no tsis muaj lub chaw kuaj xyuas kev lag luam uas muaj kev ntsuas MMP rau kev siv tshuaj kho mob.

Arosalo et al. [24] tshaj tawm txoj kev tshawb fawb sib tshooj sib piv cov nees colic uas tab tom tshawb xyuas laparotomy (nrog rau cov ntshav creatinine concentrations) rau cov nees noj qab haus huv tau txais kev castration; colic nees muaj ntau dua urinary MMP-9 complex thiab pro-MMP-9 kev ua ub no, thiab siab dua plasma MMP-2 kev ua ub no dua cov nees noj qab haus huv [24]. Cov kws sau ntawv no qhia tias kev nce hauv plasma MMP-2 kev ua haujlwm cuam tshuam nrog endotoxemia thiab qhov nce hauv cov zis MMP-9 complex thiab pro-MMP-9 cov dej num yog qhia txog AKI [24]. Yog li ntawd, kev ua haujlwm ntawm cov zis MMP tuaj yeem ua rau cov nees tau suav tias yog tus cim ntxov ntawm AKI nrog lub peev xwm los txheeb xyuas AKI cov neeg mob ua ntej cov ntshav creatinine ntau ntxiv. Tsis muaj cov ntaub ntawv kho mob (theem III), cov ntaub ntawv muaj txiaj ntsig (theem IV), cov ntaub ntawv siv los yog cov ntaub ntawv ntawm lub raum ntxiv muaj nyob rau hauv cov ntaub ntawv ntawm MMPs raws li lub raum biomarkers hauv nees.

Hauv kev xaus, tam sim no tsis muaj pov thawj rau kev kho mob ntawm MMP-9 txhawm rau kuaj kab mob raum hauv cov nees yog: qhov tsis muaj cov ntaub ntawv txheeb xyuas qhov tseeb, tsis muaj cov ntaub ntawv siv, txwv kev paub txog cov teebmeem extrarenal, tsuas yog 1 txoj kev tshawb fawb txog AKI thaum ntxov. tab sis tsis tau lees paub AKI cov ntaub ntawv muaj nyob rau hauv cov ntaub ntawv. Cov kws sau ntawv ntseeg hais tias cov ntaub ntawv tam sim no muaj nyob rau ntawm MMP-9 tsis tso cai ua cov lus hais txog nws lub peev xwm ua biomarker rau kab mob raum. Nyob rau theem no, tsis muaj cov ntaub ntawv tshawb fawb los txhawb kev kho mob siv cov biomarker no. Ntxiv mus, tam sim no tsis muaj kev sim ua lag luam rau kev kho mob

N-Acetyl-beta-D-glucosaminidase (NAG)

NAG yog ib qho loj lysosomal protein ntawm cov tubules proximal thiab tsis reabsorbed los yog lim nyob rau hauv lub glomeruli vim nws loj [50]. Yog li ntawd, ntsuas NAG hauv cov zis tau pom tias muaj txiaj ntsig zoo rau kev kuaj mob raum. Vim hais tias cov tubules ze ze yog ib feem tseem ceeb ntawm AKI pathology thiab cov kab mob mob hnyav uas feem ntau tshwm sim thaum lub sij hawm CKD, NAG yog qhov kev xav tau zoo raws li biomarker ntawm cov kab mob raum.

NAG tau raug soj ntsuam nyob rau hauv ib txoj kev tshawb no hauv nees, qhov twg ib tug photometric assay raug soj ntsuam ntawm equine zis siv ib tug biochemical analyzer [50] (Table 4). Phase 1 cov txiaj ntsig muaj los ntawm kev tshawb fawb ntawm 7 tsis yog azotemic thiab 7 azotemic nees. Lub intra-run coefficient ntawm variation rau Urine NAG / Urine Creatinine yog 20% ​​whereas lub intrarun coefficient ntawm variation yog 3.2% nrog ib tug siab linearity thaum lub sij hawm serial dilutions. NAG concentrations tau tshaj tawm tias muaj kev cuam tshuam los ntawm cov zis pH, nrog rau cov zis alkaline ua rau poob hauv cov concentration; Qhov no tuaj yeem siv tau rau hauv kev txhais lus hauv cov neeg mob equine, muab cov alkalinity ntawm cov zis equine [50]. Txawm li cas los xij, kev ua haujlwm ntxiv yog xav tau los txheeb xyuas qhov cuam tshuam ntawm qhov kev ntsuam xyuas sib txawv [51].

Txawm hais tias tus qauv me me, NAG cov ntsiab lus siab dua hauv cov nees azotemic piv rau cov nees uas tsis yog azotemic [50]. Txawm li cas los xij, tus naj npawb ntawm cov nees uas tau kawm hauv txoj kev tshawb no tsis txaus los ntsuas qhov ua tau zoo hauv kev noj qab haus huv thiab kab mob (theem II). Tsis muaj cov ntaub ntawv kho mob (theem III), cov ntaub ntawv muaj txiaj ntsig (theem IV) lossis cov ntaub ntawv siv rau cov nees muaj nyob hauv cov ntaub ntawv. Vim muaj pes tsawg tus nees nyob hauv txoj kev tshawb no, nws tsis tuaj yeem tsim cov kev siv ntau yam lossis kev kuaj pom tseeb. Hauv kev xaus, vim tsis muaj pov thawj, tsis muaj kev txhawb nqa rau kev siv tshuaj NAG ua biomarker ntawm cov kab mob raum hauv nees. NAG yuav tsum suav nrog hauv kev tshawb fawb yav tom ntej ntawm AKI thiab CKD hauv nees vim nws yuav muaj peev xwm. Raws li NAG tuaj yeem khiav ntawm kev lag luam tsom xam nws tuaj yeem yooj yim suav nrog hauv kev tshuaj ntsuam xyuas yav tom ntej. Nyob rau hauv Table 6 ib tug txheej txheem cej luam yog muab tawm ntawm molecular thiab physiological cov ntaub ntawv ntawm tag nrho cov biomarkers tham saum toj no.

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