Synergistic Impact Of Pre-sensitization Thiab Delayed Graft Function On Allograft Rejection in Deceased Donor Kidney Transplantation

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Hanbi Li^1,42, Yohan Park^1,6,42ua al

Lub hom phiaj ntawm txoj kev tshawb no yog los tshawb xyuas seb puas los yog tsis ncua kev ua haujlwm graft (DGF) thiab kev hloov pauv ua ntej muaj kev cuam tshuam tsis zoo rau cov txiaj ntsig allograft tom qab tus neeg pub dawb tuag.raumhloov pauv(DDKT) siv cov ntaub ntawv sau npe Korean Organ Transplantation Registry (KOTRY), lub teb chaws tus neeg yuav los tom ntej. Txoj kev tshawb no suav nrog 1359 tus neeg mob thaum lub Tsib Hlis 2014 txog Lub Rau Hli 2019. Cov xwm txheej tau muab faib ua 4 pawg raws li ua ntej-sensitization thiab kev loj hlob ntawm DGF tom qab hloov pauv [non - pre-sensitized - DGF(−) (n=1097} ), tsis yog pre-sensitized - DGF(ntxiv ) (n=127), pre-sensitized - DGF(−) (n=116), thiab pre-sensitized - DGF(ntxiv) (n { {11}})]. Peb piv qhov tshwm sim ntawm biopsy-proven allograft rejection (BPAR), lub sij hawm-hais txog kev hloov nyob rau hauv allograft muaj nuj nqi, allograft los yog tus neeg mob ciaj sia, thiab tom qab hloov cov teeb meem nyob rau hauv 4 subgroups. Qhov tshwm sim ntawm kev tsis lees txais cov tshuaj tiv thaiv kab mob sib kis mob hnyav (ABMR) tau nce siab dua hauv pawg ua ntej-DGF (ntxiv rau) pawg dua li lwm pawg 3 pawg. Tsis tas li ntawd, kev txheeb xyuas qhov sib txawv ntawm cox regression tau pom tias ua ntej rhiab heev ua ke nrog DGF yog ib qho kev pheej hmoo ywj pheej rau kev loj hlob ntawm ABMR mob (kev phom sij piv 4.855, 95 feem pua ntawm kev ntseeg siab 1.499–15.727). Ntxiv mus, DGF thiab pre-sensitization pom kev sib cuam tshuam tseem ceeb (p-tus nqi rau kev sib cuam tshuam=0.008). Pre-sensitization ua ke nrog DGF tsis pom qhov cuam tshuam loj rau kev ua haujlwm ntawm allograft, thiab allograft lossis tus neeg mob muaj sia nyob. Hauv kev xaus, kev sib xyaw ua ke ntawm kev xav ua ntej, thiab DGF tau pom muaj kev sib koom ua ke tseem ceeb hauv kev txhim kho allograft tsis lees paub tom qab DDKT.

cistanche extract: tiv thaiv mob raum mob

Delayed graft function (DGF) yog ib qho kev tshwm sim ntawm mob hnyavraumraug mob(AKI), uas muaj ntau dua hauv cov neeg pub dawb tuagraumhloov pauv(DDKT). Lub ntsiab txhais ntawm DGF txawv raws li txoj kev kawm; Txawm li cas los xij, nws feem ntau yog raws li kev siv lim ntshav hauv 1 lub lis piam txij li kev hloov pauv 1-3. Cov txheej txheem hauv qab ntawm kev txhim kho DGF tseem yuav tsum tau nthuav tawm, tab sis nws tau pom tias tom qab ischemic mob tubular necrosis uas tshwm sim los ntawm ischemia thiab reperfusion raug mob (IRI) txhim kho thaum lub sijhawm tuag pub dawb tswj lossis rov ua haujlwm ntawm lub cev, thiab calcineurin inhibitor (CNI) toxicity. tej zaum yuav yog tus pab txhawb nqa loj 4. Kev ua kom lub cev tiv thaiv kab mob yoog los ntawm DGF kuj ua rau muaj kev pheej hmoo ntawm allograft tsis lees paub.

Lub caij no, nws paub zoo tias qhov muaj cov neeg pub dawb tshwj xeeb los tiv thaiv tib neeg leukocyte antigen antibody (HLA-DSA), lub npe hu ua "pre-sensitized state" yog ib qho teeb meem tseem ceeb rau kev tiv thaiv kev ua tiav.raumKev hloov pauv (KT) 5-9. Hauv cov neeg mob zoo li no, HLA-DSA tuaj yeem ua rau muaj kev pheej hmoo ntawm kev mob hnyav lossis mob ntev los ntawm kev tsis lees txais tshuaj tiv thaiv kab mob sib kis (ABMR) uas ua rau muaj qhov tshwm sim tsis zoo ntawm cov txiaj ntsig 10,11. Hauv kev teeb tsa ntawm DDKT, DGF ua ke nrog kev tsis lees paub qhov chaw kho mob tau ua rau muaj qhov tshwm sim tsis zoo. Tsis tas li ntawd, qhov cuam tshuam tsis zoo ntawm DGF ntawm allograft tau txhim kho los ntawm qhov muaj kev hloov pauv ua ntej HLA-DSA hauv DDKT12.

Raws li cov keeb kwm yav dhau los saum toj no, nws muaj peev xwm hais tias DGF hauv cov neeg mob uas muaj kev nkag siab ua ntej muaj qhov cuam tshuam tsis zoo rau cov txiaj ntsig ntawm allograft. Txawm li cas los xij, nws tseem tsis tau tshawb xyuas tag nrho thiab tsuas yog ib qho kev tshawb fawb hauv ib qho chaw muaj 12. Nyob rau hauv no hais txog, lub hom phiaj ntawm txoj kev tshawb no yog los soj ntsuam cov kev sib koom ua ke ntawm DGF thiab pre- sensitization ntawm txoj kev loj hlob ntawm allograft rejection siv lub zoo-tsim nyob rau hauv lub prospective cohort, lub Korean Organ Transplantation Registry (KOTRY).

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Cistanchedeserticola extract: tiv thaivraumkab mob

Cov txiaj ntsig

Lub hauv paus chaw kho mob thiab immunological tus neeg mob yam ntxwv.

DGF tsim nyob rau hauv 10.7 feem pua (146/1359) ntawm tag nrho cov neeg tau txais DDKT. Nruab nrab ntawm cov pab pawg ua ntej thiab tsis paub ua ntej, tsis muaj qhov sib txawv hauv qhov zaus ntawm DGF (9.6 feem pua vs. 13.0 feem pua, p=0.188). Table 1 piav qhia txog cov yam ntxwv ntawm tus neeg pub dawb thiab cov neeg tau txais ntawm plaub pawg. Lub hauv paus kwv yees kwv yees glomerular filtration rate (eGFR) tau qis dua hauv cov neeg pub dawb ntawm DGF (ntxiv rau ) pawg pab pawg tsis hais txog kev nkag siab ua ntej. Lub sij hawm txias ischemic tau pom tias muaj kev nyiam ntev dua hauv DGF (ntxiv rau) pawg pab pawg tsis hais txog qhov ua ntej ua rau tsis muaj qhov tseem ceeb. Txawm li cas los xij, lub hnub nyoog pub dawb, poj niam txiv neej, lub cev qhov hnyav (BMI), kab mob hauv qab suav nrog DM lossis ntshav siab (HTN), thiab feem pua ntawm cov neeg pub dawb tom qab lub plawv tuag (DCD) lossis cov neeg pub dawb tom qab lub paj hlwb tuag (DBD) tsis txawv ntau ntawm 4 pawg. . Hauv peb txoj kev tshawb fawb, 3 tau muaj dual-raumhloov pauv los ntawm cov txheej txheem nthuav dav pub dawb, thiab 6 muaj en-blocraumtransplantation los ntawm cov me nyuam pub dawb. Txhua tus tau muab faib rau hauv pawg uas tsis yog-sensitized-DGF(−) subgroup. Tsis muaj kev hloov pauv ua ntej ua ntej.

Ntawm cov neeg tau txais txiaj ntsig, muaj qhov ntev ntev ntawm kev lim ntshav vintage thiab tseem muaj tus lej ntxiv ntawm cov poj niam cov neeg mob nyob rau hauv ob pawg ua ntej sensitized ntau dua li cov pab pawg tsis ua ntej. Raws li qhov xav tau, cov pab pawg ua ntej nkag siab tau muaj HLA tsis sib haum ntau dua. Tsis tas li ntawd, yav dhau los KT keeb kwm thiab kev faib ua feem ntawm cov tshuaj tiv thaiv thymocyte globulin (ATG) siv los ua induction therapy yog siab dua nyob rau hauv cov pab pawg ua ntej sensitized dua nyob rau hauv cov pab pawg uas tsis yog pre-sensitized. Qhov kev faib ua feem ntawm DM raws li tus kab mob hauv lub raum tau qis dua nyob rau hauv cov pab pawg ua ntej tau txais txiaj ntsig ntau dua li cov pab pawg tsis ua ntej. Ib qho kev faib ua feem ntau dua ntawm cov neeg mob uas tau txais hemodialysis raws li kev lim ntshav ua ntej KT raug xaiv los ntawm pawg tsis-pre-sensitized-DGF (ntxiv rau) pawg thaum piv nrog cov pab pawg tsis-pre-sensitized-DGF(−) subgroup. Txawm hais tias feem coob ntawm cov neeg mob tau txais tacrolimus los ua cov tshuaj tiv thaiv kab mob tseem ceeb, ntau tus neeg mob hauv DGF (ntxiv rau) pawg pab pawg pom tau tias muaj kev nyiam noj sirolimus piv nrog DGF (−) pawg.

Table 1. Comparison of clinical and laboratory parameters among the 4 subgroups according to DGF and pre-sensitization status.

Kev sib piv ntawm tag nrho biopsy-proven allograft rejection (BPAR) thiab mob ABMR.

Lub sij hawm nruab nrab rau BPAR thiab ABMR los ntawm kev hloov pauv tsis pom qhov txawv ntawm 4 pawg (BPAR, p=0.357; ABMR, p=0.318). Txawm hais tias qhov xwm txheej ntawm BPAR tag nrho tsis txawv txav ntawm 4 pawg, cov pab pawg ua ntej-DGF (ntxiv rau ) tau zoo siab dua piv rau lwm pawg 3 pawg. Qhov tshwm sim ntawm tus mob ABMR siab dua nyob rau hauv pab pawg ua ntej-DGF (ntxiv rau) pawg (21.1 feem pua, 4/19) dua li lwm pawg 3 pawg. Tag nrho, mob ABMR tshwm sim hauv 53raumCov neeg tau txais kev hloov pauv (KTRs), thiab ntawm cov no, 3 muaj de novo DSA thaum lub sijhawm kuaj ntshav. 1 yog nyob rau hauv non-pre-sensitized-DGF(−) subgroup, 1 nyob rau hauv non-pre-sensitized-DGF(ntxiv) subgroup, lwm yam nyob rau hauv pre-sensitized-DGF(ntxiv) subgroup. Qhov xwm txheej ntawm cov kab mob ABMR muaj ntau dua nyob rau hauv cov pab pawg ua ntej tau txais txiaj ntsig piv rau cov pab pawg tsis ua ntej. Hauv qhov sib piv, qhov mob hnyav thiab mob ntev T-cell mediated rejection (TCMR) tsis pom qhov sib txawv ntawm 4 pawg (Table 2).

Txawm hais tias tsis yog qhov tseem ceeb, Kaplan–Meier nkhaus tau pom tias qhov sib sau tag nrho BPAR tus nqi muaj qhov nyiam siab dua hauv pawg ua ntej-DGF (ntxiv rau ) pawg (qib qeb p=0.052) (Daim duab . 1a). ABMR acute npaum li cas yog qhov tseem ceeb tshaj plaws nyob rau hauv lub pre-sensitized-DGF (ntxiv rau ) pab pawg [log qeb; p < 0.001="" vs.="" non-pre-sensitized-dgf(−),="" p="0.004" vs.="" non-pre-sensitized-dgf(plus),="" p="0.052" vs.="" pre-sensitized="" -dgf(−)]="" (fig.="">

Kev pheej hmoo ntawm tag nrho BPAR thiab mob ABMR. Hauv cox regression tsom xam, pre-sensitization thiab DGF ib leeg tsis muaj kev pheej hmoo ntawm tag nrho BPAR [pre-sensitization, txaus ntshai piv (HR) 1.353, 95 feem pua confdence interval (CI) 0}.874–2.{{ 14}}97, p=0.176; DGF, HR 1.292, 95% CI 0.834–2.001, p=0.252]. Txawm li cas los xij, thaum qhov kev xav ua ntej thiab DGF raug coj los ua ke, nws tau los ua ib qho kev pheej hmoo ntawm kev ywj pheej rau tag nrho BPAR (unad- justed HR 2.933, 95 feem pua CI 1.299–6.619, p=0.010, kho HR 2.663, 95 feem pua. CI 1.087–6.525, p=0.032) (Table 3a).

Hais txog tus mob ABMR, thaum DGF ib leeg tsis yog ib qho kev pheej hmoo ntawm kev ywj pheej (HR 1.787, 95 feem pua CI 0.872–3.660, p=0.113), kev nkag siab ua ntej tau txuam nrog ib qho tseem ceeb HR (HR 2.977, 95 feem pua CI 1.592–5.566, p=0.001). Hauv kev txheeb xyuas kev sib cuam tshuam, kev sib xyaw ua ke ntawm kev xav ua ntej thiab DGF muaj ntau dua HR (unad- justed HR 6.666, 95 feem pua CI 2.404–18.481, p < 0.001,="" kho="" hr="" 4.855,="" 95="" feem="" pua="" ci="" 1.499–15.7327,="" p.="" }.008)="" (table="">

Table 2. Comparison of rejection-related outcomes among the 4 subgroups according to DGF and presensitization status.

Kev sib piv ntawm kev hloov pauv hauv kev ua haujlwm ntawm allograft thiab kev tuag-censored allograft ciaj sia taus.

Txij li cov ntaub ntawv hais txog seb cov neeg tau txais KT puas tau lim ntshav thaum lub sijhawm tso tawm tsis muaj, cov ntshav creatinine los ntawm 6- hli tom qab hloov pauv tau siv los sib piv cov haujlwm allograft thoob plaws 4 pawg. Thaum lub sijhawm 3- xyoo rov qab, allograft muaj nuj nqi ntsuas los ntawm eGFR siv covmob ntevraumkab mob-epidemiology kev sib koom ua ke (CKD-EPI) qhov sib npaug poob qis hauv pawg tsis-pre-sensitized-DGF(ntxiv) pawg. Thaum qhov kev hloov pauv ntawm lub sijhawm cuam tshuam txog kev ua haujlwm ntawm 12 lub hlis los ntawm cov hauv paus ntsiab lus ntawm cov pawg tsis-pre-sensitized-DGF(−) subgroup yog qhov sib txawv ntawm cov uas tsis yog-pre-sensitized-DGF(ntxiv) hauv cov kab sib xyaw. qauv (p=0.007), lwm pab pawg tsis pom qhov txawv txav. Te hloov nyob rau hauv lub sij hawm hais txog allograft muaj nuj nqi nyob rau lwm lub sij hawm cov ntsiab lus tsis pom qhov txawv tseem ceeb nyob rau hauv 4 subgroups (p=0.435 ntawm 24 lub hlis, p=0.059 ntawm 36 lub hlis) (Fig. 2).

Tag nrho, 41 qhov teeb meem ntawm allograft tsis ua haujlwm tau tsim nyob rau lub sijhawm ua raws. Lub sijhawm nruab nrab ntawm kev ua haujlwm ntawm graf tsis ua haujlwm hauv txhua pab pawg tsis pom qhov txawv txav [non-pre-sensitized-DGF(−) 37.5 (interquartile range (IQR) 25.0–50.6 ], non-pre-sensitized-DGF(plus ) 36.8 (IQR 21.7–58.3), pre-sensitized-DGF(−) 37.7 (IQR 23.6–47.36), thiab pre-sensitized-DGF(plus ) 36.0 (IQR 17. 44.1) hli, p=0.610). Lub ntsiab tseem ceeb ua rau kev poob nyiaj poob haujlwm yog kev tsis lees paub (15/41, 36.6 feem pua). Ntawm cov no, 5 tau txais kev kho mob tsis lees paub, thiab 10 muaj BPAR. Mob ABMR tshwm sim nyob rau hauv 6/15 (40 feem pua), ntawm uas 5 nyob rau hauv lub non-pre-sensitized-DGF (−) pawg thiab 1 nyob rau hauv lub pre-sensitized-DGF (−) subgroup. Nyob rau hauv pawg uas tsis yog-sensitized-DGF(−) subgroup, kev tsis lees paub yog lub ntsiab ua rau poob allograft (11/30, 36.7 feem pua), tom qab los ntawm tsis paub (10/30, 33.3 feem pua). Nyob rau hauv pawg neeg uas tsis yog-pre-sensitized-DGF (ntxiv rau) subgroup, lub ntsiab ua rau allograft poob yog tsis lees paub (3/8, 37.5 feem pua). Hauv pab pawg ua ntej-DGF (−) pawg, ob qho kev tsis lees paub (1/3, 33.3 feem pua) thiab cov teeb meem tom qab phais (1/3, 33.3 feem pua) suav rau tib qhov kev faib ua feem. Hauv pawg ua ntej-sensitized-DGF(ntxiv) subgroup, tsis muaj allograft poob lawm. Te Kaplan–Meier nkhaus tsis muaj qhov sib txawv tseem ceeb hauv kev tuag-censored allograft ciaj sia taus ntawm 4 pawg (log-rank p=0.114) (Fig. 3).

Kev sib piv ntawm cov neeg mob ciaj sia thiab cov teeb meem tom qab hloov pauv. Tag nrho ntawm 55 (4.0 feem pua ) cov neeg mob tuag hauv peb pawg vim muaj kab mob plawv hauv 9 tus neeg mob, kis mob hauv 26, mob qog noj ntshav hauv 4, lwm tus (mob siab, mob hlwb, mob CNI toxicity, plab hnyuv los ntshav, mob tsis lees paub, thiab lwm yam) hauv 11, thiab tsis paub etiology hauv 5 kis. Hauv txhua pab pawg, 37 (3.4 feem pua ) tuag nyob rau hauv pawg uas tsis yog-sensitized-DGF(−) subgroup, 14 (11.0 feem pua ) nyob rau hauv pre-sensitized-DGF(ntxiv) subgroup, 4 (3.4 feem pua ) hauv pawg ua ntej-DGF(−) subgroup, thiab tsis muaj (0.0 feem pua ) nyob rau hauv pawg pre-sensitized-DGF(ntxiv) subgroup. Tag nrho cov neeg tuag yog qhov siab tshaj plaws nyob rau hauv pawg uas tsis yog-sensitized-DGF(ntxiv) subgroup (p=0.001) (Table 4a).

Tsis muaj qhov sib txawv tseem ceeb hauv kev txhim kho ntawm BK tus kab mob ntsig txog nephropathy (BKVAN), kab mob cerebrovascular, kab mob sib kis, thiab mob qog noj ntshav thoob plaws 4 pawg (Table 4b).

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Dab tsi yog cistanche siv rau: kho mob raum kab mob

Kev sib tham

Pre-sensitization rau HLA yog qhov paub zoo ua ntej hloov pauv, uas tuaj yeem ua rau muaj kev pheej hmoo rau allograft rejection thiab allograft tsis ua haujlwm. Lub caij no, DGF yog qhov paub zoo tom qab hloov pauv, uas tseem ua rau cov txiaj ntsig tsis zoo. Txoj kev tshawb no pom tau hais tias kev sib xyaw ua ke ntawm kev hloov pauv tom qab hloov pauv (DGF) thiab kev pheej hmoo ntawm kev hloov pauv ua ntej (pre-sensitization) tau muaj kev cuam tshuam tsis zoo rau cov txiaj ntsig ntawm allograft, tshwj xeeb tshaj yog qhov tshwm sim ntau dua ntawm allograft rejection.

Ua ntej, peb piv cov yam ntxwv ntawm cov neeg pub dawb thiab cov neeg tau txais thoob plaws 4 pawg kho mob. Nyob rau hauv cov nqe lus ntawm tus neeg pub khoom, lub hauv paus raum kev ua haujlwm tau qis dua hauv cov neeg mob uas tau pom DGF, uas tau ua raws li cov kev tshawb fawb yav dhau los, uas tau tshaj tawm tias lub raum tsis ua haujlwm hauv lub raum yog qhov pheej hmoo rau DGF13. Hauv qhov sib piv, tsis muaj qhov sib txawv tseem ceeb ntawm qhov zaus ntawm DGF ntawm cov pab pawg ua ntej thiab tsis muaj kev nkag siab ua ntej, uas qhia tias kev hloov pauv ua ntej yuav tsis muaj txiaj ntsig zoo rau kev txhim kho DGF. Ntawm cov neeg tau txais txiaj ntsig, kev lim ntshav tau ntev ntev hauv cov pab pawg ua ntej tau txais kev nkag siab, uas tau qhia tias cov neeg tau txais txiaj ntsig xav tau lub sijhawm tos ntev dua rau DDKT faib 14–16. Raws li qhov xav tau, qhov feem pua ntawm cov poj niam tau txais ntau dua nyob rau hauv ob pawg neeg ua ntej 15 thiab feem pua ntawm cov neeg tau txais nrog KT keeb kwm yav dhau los tau siab dua thiab zoo li siab dua nyob rau hauv ob pawg ua ntej sensitized ntau dua li cov pab pawg tsis ua ntej. Tsis tas li ntawd, txawm hais tias feem coob ntawm cov neeg mob tau txais kev tiv thaiv kev tiv thaiv thawj zaug nrog tacrolimus, cov neeg mob ntau dua tau txais cov tshuaj sirolimus hauv pawg uas tsis yog-sensitized-DGF (ntxiv rau ) pawg. Qhov kev tshawb pom no tau qhia tias cov kws kho mob tau txiav txim siab hloov ntawm CNI mus rau lub hom phiaj ntawm cov tsiaj nyeg ntawm rapamycin (mTOR) inhibitor, vim tias CNI tuaj yeem pab txhawb kev rov qab qeeb ntawm allograft function17.

Table 3. Multivariable Cox regression for independent predictors of (a) overall BPAR and (b) acute ABMR. (a) Multivariable regression model was adjusted with parameters showing signifcant diferences in univariable analysis or known to afect overall BPAR.

Qhov thib ob, peb piv qhov tshwm sim ntawm tag nrho BPAR raws li kev xav ua ntej lossis kev txhim kho ntawm DGF. Raws li qhov tshwm sim, qhov tshwm sim ntawm BPAR tag nrho pom tias muaj kev nyiam siab dua hauv pawg ua ntej-DGF (ntxiv rau) pawg, thiab qhov mob ABMR yog qhov siab tshaj plaws hauv pawg ua ntej-DGF (ntxiv) pawg. Interestingly, pre- sensitization thiab DGF pom muaj kev cuam tshuam nrog ib leeg, uas qhia lawv synergistic cuam tshuam rau txoj kev loj hlob ntawm tag nrho cov BPAR thiab mob ABMR. Cov nyiaj no tuaj yeem piav qhia los ntawm ob yam. Ua ntej, DGF per se tuaj yeem ua rau muaj kev tiv thaiv kab mob ntawm allograft, thiab yog li ua rau muaj qhov tsis zoo rau cov tshuaj tiv thaiv kab mob ua ntej HLA-DSA. Tseeb tiag, IRI hauv DGF tuaj yeem tswj hwm qhov loj histocompatibility complex (MHC) chav kawm I thiab II antigens, thiab txhim kho kev qhia ntawm adhesion thiab costimulatory molecules ntawm allograft cov ntaub so ntswg18-21. Ntxiv mus, IRI induces ligands ntawm tus xov tooj hu-zoo li receptors (TLRs) thiab activates hlwb ntawm lub innate lub cev tiv thaiv kab mob, inducing activation thiab maturation ntawm dendritic hlwb, ua raws li los ntawm adaptive immune teb21. Qhov tseeb, cov kev tshawb fawb yav dhau los tau pom tias DGF muaj feem cuam tshuam nrog kev pheej hmoo siab ntawm allograft poob thiab raug tsis lees paub 22,23. Qhov thib ob, kev hloov pauv ntawm CNI rau mTOR inhibitor tau tshawb pom ntau dua hauv cov neeg mob uas raug kev txom nyem los ntawm DGF hauv txoj kev tshawb no, tej zaum vim tias CNI yuav raug suav hais tias yog tus pab txhawb rau DGF. Kev txo qis qis zog ntawm mTOR inhibitor rau kev tiv thaiv kab mob hauv lub cev hauv kev sib piv nrog tacrolimus yog lwm qhov ua rau ntawm tus nqi siab dua ntawm ABMR nyob rau hauv pre-sensitized-DGF (ntxiv rau) pawg 24.

Figure 2. Comparison of the time-related changes in allograf function based on eGFR using CKD-EPI equation (mL/min/1.73 m2 ) according to DGF and pre-sensitization status.

Kuj ceeb tias, ua ntej rhiab heev lossis DGF per se tsis muaj qhov cuam tshuam loj rau kev loj hlob ntawm BPAR tag nrho. Yog vim li cas tsis paub meej, tab sis nws yuav raug ntaus nqi los ntawm kev txwv tsis pub dhau ntawm ob qho tib si pre-sensitization thiab DGF nyob rau hauv txoj kev tshawb no siv ib tug thoob lub teb chaws cohort, retrospectively. Nyob rau hauv cov ntaub ntawv ntawm pre-sensitization, txij li thaum cov ntaub ntawv ntawm DSA tau sau nyob rau hauv 2017, cov txiaj ntsig ntawm HLA-DSA tsis muaj nyob rau hauv qee tus neeg tau txais. Yog li ntawd, hauv cov neeg tau txais txiaj ntsig zoo li no, peb tau txiav txim siab qhov kev xav rau HLA los ntawm kev muaj vaj huam sib luag cov tshuaj tiv thaiv kab mob (PRA), ua ke nrog cov txiaj ntsig zoo crossmatch xeem. Txawm hais tias qhov kev txhais no yog siv rau "pre-sensitization", peb tsis tuaj yeem ntsuas qhov kev xav tau kom meej. Nyob rau hauv rooj plaub ntawm DGF, lub ntsiab lus ntawm DGF yog txawv ntawm cov kev tshawb fawb yav dhau los25. Tseeb, lub ntsiab lus ntawm DGF tsuas yog nyob ntawm qhov ua tau zoo ntawm kev lim ntshav tom qab KT, thiab qhov kev txiav txim siab seb puas yuav ua lim ntshav tuaj yeem txawv raws li cov chaw hloov pauv. Tsis tas li ntawd, vim tsis muaj cov ntaub ntawv ntxaws ntxaws, ib qho kev tiv thaiv kev tiv thaiv tus kheej raws li kev pheej hmoo ntawm kev tiv thaiv kab mob thiab cov qib ntshav ntawm cov tshuaj tiv thaiv kab mob hauv txhua tus neeg tau txais kev pab tsis tau txiav txim siab hauv peb qhov kev tshuaj ntsuam. Yog li ntawd, cov lus hais saum toj no tuaj yeem ua rau muaj kev tsis ncaj ncees uas tuaj yeem cuam tshuam qhov txiaj ntsig ntawm txoj kev tshawb no.

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cistanche tubolosa testosterone: tiv thaiv kev laus

Interestingly, pab pawg neeg uas tsis yog-sensitized-DGF (ntxiv) tau pom qhov ua haujlwm tsis zoo tshaj plaws ntawm 36 lub hlis tom qab hloov pauv hloov. Ib qho laj thawj yog vim li cas yog lub hauv paus txheej xwm ntawm tus neeg mob lub raum sib xws (Table 1). Cov neeg pub dawb ntawm pab pawg no tau pom tias lub raum ua haujlwm qis dua ntawm lub hauv paus, lub sijhawm txias ischemic ntev, thiab siab duaraumtus qhab nia pub dawb profile (KDPI), txawm tias tsis tseem ceeb. Txhua qhov kev tshawb pom yav dhau los qhia tau hais tias lub hauv paus txheej xwm ntawm tus neeg pub lub raum yog qhov phem tshaj plaws hauv pab pawg no, uas yuav ua rau muaj kev ua haujlwm tsis zoo ntawm allograft. Hais txog kev ua haujlwm ntawm allograft, qhov cuam tshuam ntawm lub hauv paus raum kev ua haujlwm tuaj yeem tseem ceeb dua li kev tsis lees paub allograft thaum lub sijhawm ua raws li kev txwv. Yog li ntawd, kev muaj sia nyob ntawm allograft tsis txawv ntawm 4 pawg sub.

Figure 3. Kaplan–Meier estimates of death-censored allograf survival according to DGF and pre-sensitization status.

Thaum kawg, peb piv cov teeb meem tom qab hloov pauv ntawm 4 pawg sub. Non-pre-sensitized-DGF(ntxiv) pab pawg tau pom tias tus neeg mob tuag ntau dua. Txawm li cas los xij, tsuas yog 55 tus neeg mob ntawm 1359 KTRs tau pom thiab tsis muaj tus neeg mob tuag hauv pawg ua ntej-DGF (ntxiv rau ) pawg. Yog li ntawd, kev soj ntsuam ntev dua yuav tsum tau los txog ntawm txhua qhov kev txiav txim siab. Muab piv nrog cov teeb meem tom qab hloov pauv, tsis muaj qhov sib txawv ntawm 4 pawg hauv kev txhim kho BKVAN, kab mob plawv, kab mob cerebrovascular, kab mob, thiab malignancy. Txawm li cas los xij, kev tshawb nrhiav ntxiv yuav tsum tau hais kom meej txog qhov teeb meem no26.

Txoj kev tshawb no muaj qee qhov kev txwv. Ua ntej, qhov kev ntsuam xyuas kev sau npe thoob tebchaws no cuam tshuam cov kev txwv zoo sib xws hauv cov ntawv sau npe loj zoo sib xws raws li qhia hauv peb cov kev tshawb fawb yav dhau los27. Thaum cov neeg mob cov lej tau txhim kho, cov ntsiab lus tseem ceeb rau cov ntsiab lus kawg tau ploj lawm, yog li txo qhov kev siv tshuaj kho mob ntawm qhov kev tshawb pom. Piv txwv li, HLA-DSA tsis muaj rau kev tshuaj xyuas hauv qee tus neeg mob (22.6 feem pua ). Tsis tas li ntawd, MFI txiav tawm los txiav txim siab qhov zoo ntawm cov chaw zov me nyuam tsis muaj, thiab peb tsis tuaj yeem siv cov chav kawm thiab lub zog ntawm DSA hauv kev tshuaj xyuas, uas tau tshaj tawm tias yog ib qho tseem ceeb ntawm kev pheej hmoo rau allograft tsis lees paub thiab ua tsis tiav6,10,28– 30. Qhov thib ob, lub sijhawm ua raws li qhov kev sau npe no raug txwv raws li tau hais dhau los. Yog li ntawd, ib txwm muaj feem cuam tshuam rau allograft tsis ua hauj lwm xws li DGF thiab pre-sensitization tsis cuam tshuam rau allograft cov txiaj ntsig. Qhov thib peb, peb tsis tuaj yeem txiav txim siab txog cov txheej txheem teev tseg ntawm txhua qhov chaw hauv DDKT rau cov neeg tau txais txiaj ntsig zoo heev, xws li desensitization thiab soj ntsuam biopsy raws tu qauv. Txawm hais tias kev hloov pauv ua ntej desensitization tau ua nyob rau hauv 35 tus neeg tau txais kev pab, suav nrog cov neeg uas muaj B-cell crossmatch zoo, tsis muaj cov ntaub ntawv muaj nyob rau ntawm txoj cai. Qee lub chaw siv rituximab los kho cov neeg mob zoo li no, thiab lwm tus tsis tau, tab sis hmoov tsis, nws tsis tau txiav txim siab hauv qhov kev tshuaj ntsuam no. Txawm li cas los xij, peb txoj kev tshawb fawb yog qhov kev tshawb fawb ntau lub hauv paus los tshawb xyuas lub koom haum ntawm DGF thiab kev nkag siab ua ntej hauv cov txiaj ntsig allograft.

Hauv kev xaus, peb tau pom tias kev sib xyaw ua ke ntawm DGF thiab kev nkag siab ua ntej rau HLA muaj kev cuam tshuam tsis zoo rau cov txiaj ntsig allograft nyob rau hauv cov nqe lus ntawm kev tsis lees paub. Yog li ntawd, peb xav tias yuav tsum tau saib xyuas kom zoo dua lossis kev soj ntsuam ntawm allograft rejection. Tsis tas li ntawd, peb yuav tsum tau siv cov txheej txheem tiv thaiv kab mob ntau dua los tiv thaiv kev tsis lees paub thaum DGF tshwm sim hauv DDKT nrog kev ua ntej.

Table 4. (a) Causes of death and (b) clinical outcomes among the 4 subgroups according to DGF and pre-sensitization status

Cov txheej txheem

Kawm cov pej xeem.

Peb tau txheeb xyuas KOTRY cov ntaub ntawv los ntawm Kaus Lim Kauslim Society for Transplantation31, sau cov ntaub ntawv los ntawm 30 lub raum hloov chaw hauv Kaus Lim Kauslim32. Te KOTRY cov ntaub ntawv suav nrog 1945 DDKT rooj plaub thaum lub Tsib Hlis 2014 thiab Lub Rau Hli 2019, los ntawm qhov uas peb tsis suav nrog 586 DDKT cov neeg tau txais nrog cov ntaub ntawv tsis muaj txog PRA, HLA-DSA, kev sib tw sib tw, lossis kev txhim kho DGF, thiab nrog thawj qhov tsis ua haujlwm ntawm lub raum allograft. Yog li ntawd, peb suav nrog 1359 tus neeg tau txais DDKT hauv qhov kev tshawb nrhiav tam sim no thiab faib cov neeg mob ua plaub pawg raws li kev nkag siab ua ntej thiab kev txhim kho ntawm DGF tom qab hloov pauv: tsis ua ntej-sensitized- DGF(−) (n=1097 ), non-pre-sensitized-DGF( plus ) (n=127), pre-sensitized-DGF(−) (n=116), pre-sensitized- DGF(plus ) (n {{ 25}}) (Fig. 4). Lub sijhawm nruab nrab ntawm qhov kev tshawb fawb no yog 38.1 (IQR 25.2–50.8) lub hlis.

Peb tau txiav txim siab ua ntej rau HLA los ntawm qhov muaj (i) HLA-DSA (los ntawm Luminex ib qho tshuaj tiv thaiv kab mob) lossis (ii) PRA (los ntawm kev tshuaj ntsuam xyuas HLA antibody), ua ke nrog cov txiaj ntsig zoo sib xws. HLA-DSA cov ntaub ntawv muaj nyob rau hauv 1052 tus neeg tau txais (77.4 feem pua). Yog li ntawd, qhov rhiab heev rau HLA tau txhais los ntawm kev kuaj pom HLA-DSA hauv cov neeg mob. Hauv lwm qhov 307 (22.6 feem pua) DDKT cov neeg tau txais kev pab rau cov neeg uas HLA-DSA cov ntaub ntawv tsis muaj, peb tau txiav txim siab rhiab heev rau HLA raws li cov txiaj ntsig zoo ntawm PRA thiab kev sib tw sib tw, tsis hais seb puas muaj kev cuam tshuam nrog cytotoxicity lossis flow cytometry. DGF tau txhais raws li qhov xav tau rau kev lim ntshav hauv 1 lub lis piam ntawm kev hloov pauv. Cov ntaub ntawv kho mob raug tshuaj xyuas tom qab tau txais kev tso cai pom zoo32. Txoj kev tshawb no tau ua raws li Kev Tshaj Tawm ntawm Helsinki thiab Tshaj Tawm ntawm Istanbul. Txoj kev tshawb no tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm Seoul St. Mary's Tsev Kho Mob (KC14ONMI0460).

Figure 4. Distribution of the patient population according to DGF or pre-sensitization to HLA. DGF delayed graf function, HLA human leukocyte antigen, DDKT deceased donor kidney transplantation, DSA donorspecifc antibody

Kev txhais cov txiaj ntsig kho mob.

Cov txiaj ntsig tau soj ntsuam hauv qhov kev tshawb fawb no suav nrog qhov tshwm sim ntawm BPAR tag nrho, mob ABMR, lub sijhawm hloov pauv hauv kev ua haujlwm allograft ntsuas raws li eGFR, kev tuag-censored allograft ciaj sia taus tus nqi, thiab tom qab hloov cov teeb meem xws li BKVAN, kab mob plawv, kab mob cerebrovascular, kab mob, thiab malignancy. BPAR tau kuaj pom raws li Banf 2013 classifcation33. Kev tsis lees paub-dawb allograft muaj sia nyob tau txhais tau tias yog lub sijhawm dhau los ntawm kev hloov pauv mus rau frst rov ntawm BPAR. Cov qib creatinine hauv cov ntshav tau sau rau ntawm rau lub hlis thiab tom qab ntawd ntawm ib xyoos tom qab hloov pauv. Te eGFR rau txhua lub sijhawm sib koom ua ke tau soj ntsuam siv CKD-EPI equation34. Allograft ciaj sia taus tau txhais tias yog lub sij hawm los ntawm kev hloov mus rau qhov pib nrog rau lwm txoj kev kho raum hloov. Kab mob plawv yog txhais tau tias yog mob plawv tuag, myocardial infarction, kab mob plawv ischemic nrog cov ntaub ntawv pov thawj kho mob (nrog rau kev kho mob lossis kev tshawb pom lub hom phiaj), qhov pib mob plawv tsis ua haujlwm tshiab yuav tsum tau mus pw hauv tsev kho mob, thiab arrhythmia. Cov kab mob cerebrovascular suav nrog cov kab mob uas tsis yog mob hemorrhagic lossis ischemic hlwb paub tseeb los ntawm kev suav tomography lossis sib nqus resonance imaging32. BKVAN tau kuaj pom los ntawm kev kuaj ntshav kuaj ntshav. Txhua qhov chaw kho mob tau muab piv rau ntawm plaub pawg neeg mob.

Txoj kev txheeb cais.

Tag nrho cov kev hloov pauv tsis tu ncua tau qhia tias txhais tau tias ± tus qauv sib txawv. Yog tias qhov hloov pauv tau ua raws li qhov kev faib tawm ib txwm, kev tshuaj ntsuam ntawm qhov sib txawv (ANOVA) tau ua. Yog tias qhov sib txawv tau pom tias tsis yog ib txwm faib, Kruskal-Wallis xeem tau ua. Tukey txoj kev los yog Mann-Whitney xeem tau ua raws li kev soj ntsuam tom qab doc. Tag nrho cov kev sib txawv categorical tau muab piv nrog qhov kev xeem chi-square los yog Fisher qhov kev xeem thiab qhia raws li proportions. Tshem tawm-censored allograft rejection tus nqi thiab kev tuag-censored allograft ciaj sia taus tus nqi raug soj ntsuam los ntawm kev siv lub Kaplan-Meier ciaj sia taus tsom xam thiab tau muab piv nrog rau cov log-qib xeem. Cov teebmeem ntawm DGF thiab pre-sensitization thiab kev cuam tshuam ntawm DGF thiab pre-sensitization ntawm tag nrho BPAR los yog mob ABMR raug soj ntsuam los ntawm Cox proportional-hazards regression analysis. Lub hauv paus kev soj ntsuam thiab kuaj tsis pom qhov sib txawv tseem ceeb (p-value < {{10}}}.05)="" hauv="" kev="" tshuaj="" ntsuam="" tsis="" sib="" xws="" lossis="" paub="" tias="" cuam="" tshuam="" rau="" allograft="" rejection="" tau="" haum="" rau="" hauv="" cov="" qauv="" sib="" txawv.="" peb="" xaiv="" cov="" khoom="" pub="" dawb="" (lub="" sijhawm="" txias="" ischemic,="" kdpi)="" thiab="" cov="" neeg="" tau="" txais="" txiaj="" ntsig="" (bmi,="" lub="" sijhawm="" lim="" ntshav,="" tus="" lej="" tsis="" sib="" haum,="" yav="" dhau="" los="" kt="" keeb="" kwm,="" pra=""> 50 feem pua) raws li kev tsis sib haum xeeb. Lub sij hawm hais txog allograft muaj nuj nqi ntawm pawg sub yog muab piv nrog cov qauv sib xyaw linear. Qhov kev soj ntsuam zaum kawg nqa mus tom ntej (LOCF) kev tshuaj xyuas tau siv rau qhov tsis muaj eGFR qhov tseem ceeb. Tag nrho cov ntaub ntawv uas ploj lawm tau censored los ntawm hnub ua ntej kawg. p qhov tseem ceeb <0.05 yog="" qhov="" tseem="" ceeb.="" txhua="" qhov="" kev="" txheeb="" cais="" tau="" ua="" tiav="" siv="" spss®="" software,="" version="" 24="" (ibm="" corporation,="" armonk,="" ny,="" usa)="" thiab="" microsoft="" excel="">

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Cov ntaub ntawv muaj

Cov ntaub ntawv tsim tawm thaum lub sijhawm thiab / lossis tshuaj xyuas thaum lub sijhawm kawm tam sim no muaj los ntawm tus kws sau ntawv raws li kev thov tsim nyog.

Cov ntaub ntawv

1. Agarwal, A., Murdock, P. & Fridell, JA Kev sib piv ntawm histidine-tryptophan ketoglutarate tov thiab University of Wisconsin cov tshuaj nyob rau hauv lub caij txias preservation ntawm lub raum allografts. Kev hloov pauv 81, 480–482. (2006).

2. Roels, L. et al. Cov txiaj ntsig tsis zoo ntawm lub raum cadaveric khaws cia rau ntau tshaj 24 teev hauv cov tshuaj histidine-tryptophan-ketoglutarate. Leuven Collaborative Group for Transplantation. Kev hloov pauv 66, 1660–1664.

3. Yarlagadda, SG et al. Cov cim kev hloov pauv hauv lub ntsiab lus thiab kev kuaj mob ncua sij hawm graft muaj nuj nqi: Kev tshuaj xyuas zoo. Nephrol.Dial. Hloov. 23, 2995–3003, ib.

4. Schroeppel, B. & Legendre, C. Ncua lub raum graf muaj nuj nqi: los ntawm cov txheej txheem rau kev txhais lus. Raum Int. 86, 251–258.

5. Sethi, S. et al. Desensitization: kov yeej cov kab mob immunologic rau kev hloov pauv. J. Immunol. Res.

6. Chung, BH et al. Kev soj ntsuam kev cuam tshuam ntawm lub hauv paus pub dawb-tshwj xeeb los tiv thaiv tib neeg leukocyte antigen antibody ntsuas los ntawm Luminexsingle antigen assay nyob rau hauv cov neeg pub lub raum hloov cov neeg tau txais kev pab tom qab desensitization kho. Transpl. Int. 27, 49–59 : kuv.

7. Hariri, A. et al. Qhov zoo ntawm kev sib tw ua neej nyob pub rau lub raum hloov pauv: Cov txiaj ntsig ntev ntev ntawm kev sau ntawv tawm tswv yim. J. Urol.182, 1138–1138 (2009).

8. Marfo, K., Lu, A., Ling, M. & Akalin, E. Desensitization raws tu qauv thiab lawv qhov tshwm sim. Clin. J. Am. Soc. Nephrol. 6, 922–936 : kuv.

9. Caro-Oleas, JL et al. Kev soj ntsuam qhov cuam tshuam ntawm HLA pub dawb-cov tshuaj tiv thaiv tshwj xeeb uas kuaj pom los ntawm ib qho tshuaj tiv thaiv kab mob hauv lub raum hloov pauv. Nephrol. Hu rau. Transpl. 27 Ib., 1231–1238.

10. Lefaucheur, C. et al. Preexisting pub-specific HLA antibodies kwv yees qhov tshwm sim hauv kev hloov raum. J. Am. Soc. Nephrol. 21, 1398–1406.

11. Mohan, S. et al. Cov tshuaj tiv thaiv tshwj xeeb pub dawb cuam tshuam rau lub raum allograft cov txiaj ntsig. J. Am. Soc. Nephrol. 23 Ib., 2061–2071.

12. Haller, J. et al. Qhov sib txawv ntawm kev ncua sij hawm graft muaj nuj nqi hauv cov neeg tuag pub rau lub raum hloov cov neeg tau txais nrog thiab tsis muaj tus neeg pub dawb tshwj xeeb HLA-antibodies. Kev hloov pauv 103, e273–e280.

13. Mannon, RB Delayed graf function: Te AKI ntawm lub raum hloov. 140, 94–98.

14. Keith, DS & Vranic, GM Txoj hauv kev rau tus neeg sib tw hloov lub raum rhiab heev. Clin. J. Am. Soc. Nephrol. 11, 684–693 : kuv.

15. Bostock, IC thiab al. Qhov tshwm sim ntawm cov neeg tuag pub raum hloov pauv raws li feem pua PRA. Transpl. Immunol. 28, 154–158.

16. Jeon, HJ et al. Cov txiaj ntsig ntawm cov neeg mob raum raum kawg ntawm cov neeg mob nyob rau hauv cov npe tos rau cov neeg tuag pub rau lub raum hloov pauv: Ib qho kev tshawb fawb ib leeg. Lub raum Res. Clin. Xyaum. 38, 116–123, ib.

17. Diekmann, F. et al. Sequential quadruple immunosuppression nrog rau sirolimus nyob rau hauv cov txheej txheem txuas ntxiv thiab tsis yog lub plawv dhia pub rau lub raum hloov pauv. Kev hloov pauv 84, 429–432.

18. de Sandes-Freitas, TV et al. Lub sijhawm ncua sij hawm graft muaj feem cuam tshuam nrog cov neeg mob qis dua thiab lub raum allograft muaj sia nyob. PLoS ONE 10, e0144188.

19. Shoskes, DA, Parfrey, NA & Halloran, PF Nce loj histocompatibility complex antigen qhia nyob rau hauv unilateral ischemic mob tubular necrosis nyob rau hauv nas. Kev hloov pauv 49, 201–207.

20. Doshi, MD, Garg, N., Reese, PP & Parikh, CR Cov neeg txais kev pheej hmoo cuam tshuam nrog kev ncua sij hawm graft ua haujlwm: Kev soj ntsuam ob lub raum. Kev hloov pauv 91, 666–671.

Inhibition Ntawm Crandell-Rees Feline Raum Cell Proliferation Los Ntawm X-ray-induced Senescence

Lub raum cov ntaub so ntswg Elasticity Los ntawm Acoustic Radiation Force Impulse