Erythropoietin-Stimulating Agent Hyporesponsiveness nyob rau hauv cov neeg mob nyob nrog mob raum kab mob

Abstract

1. Keeb kwm

Erythropoietin-stimulating tus neeg saib xyuas (ESA) hyporesponsiveness feem ntau pom nyob rau hauv cov neeg mob ntshav qab zib theem nrab mus rau mob raum mob (CKD). Vim tias nws txoj kev nyuaj, kev pom zoo thoob ntiaj teb ntawm qhov peb yuav tsum txhais li cas ESA hyporesponsiveness tseem tsis muaj. Cov ntaub ntawv tshaj tawm thiab cov ntaub ntawv pej xeem ntawm ESA hyporesponsiveness nyob rau hauv cov pej xeem CKD yog qhov sib txawv uas tsis muaj kev pom zoo txhais.

2. Cov ntsiab lus

ESA hyporesponsiveness txhais tau tias tsis muaj qhov nce hauv hemoglobin concentration los ntawm cov hauv paus ntsiab lus tom qab thawj lub hlis ntawm kev kho mob ntawm kev noj tshuaj raws li qhov tsim nyog. Cov yam tseem ceeb uas cuam tshuam nrog ESA hyporesponsiveness muaj xws li cov hlau tsis muaj peev xwm, kev mob, thiab uremia. Hepcidin tau pom tias ua lub luag haujlwm tseem ceeb hauv cov txheej txheem no. Mineral pob txha kab mob thib ob rau CKD thiab tsis muaj hlau tsis txaus ntawm lwm yam kuj tseem cuam tshuam nrog ESA hyporesponsiveness. Muaj kev sib cav txuas ntxiv mus rau kev txiav txim siab txoj kev kho mob kub los tswj ESA hyporesponsiveness. Kev txhim kho ntawm hypoxia-inducing factor stabilizers coj cov kev nkag siab tshiab thiab cov hauv kev hauv kev tswj hwm ntawm ESA hyperresponsiveness.

3. Ntsiab lus

Kev tswj hwm ntawm ESA hyporesponsiveness suav nrog kev qhia ntau yam pab pawg neeg txoj hauv kev los daws nws cov kev pheej hmoo. Kev nce qib ntawm cov kev tshawb fawb hauv paus thiab kev kho mob ntawm kev txheeb xyuas cov xwm txheej txaus ntshai thiab kev tswj hwm ntawm ESA hyporesponsiveness ua rau muaj kev cia siab ntau dua hauv kev nrhiav kev daws teeb meem thaum kawg los daws ib qho teeb meem nyuaj tshaj plaws hauv cov ncauj lus ntawm anemia hauv CKD.

Ntsiab lus

Anemia · Erythropoietin-stimulating agent · Hyporesponsiveness · Mob raum mob.

Nyem qhov no kom paub seb cov txiaj ntsig Cistanche yog dab tsi

Taw qhia

Anemia feem ntau pom nyob rau hauv cov neeg mob uas muaj kab mob raum ntev (CKD) thiab cuam tshuam nrog cov txiaj ntsig tsis zoo [1]. Txij li thaum tau txais kev pom zoo los ntawm US FDA xyoo 1989, erythropoietin-stimulating agents (ESAs) sawv cev rau tus kws kho mob tseem ceeb hauv kev tswj ntshav qab zib rau cov neeg mob CKD siab heev. USRDS 2020 Daim ntawv tshaj tawm Cov Ntaub Ntawv Txhua Xyoo tau hais txog ntau dua 85 feem pua ​​​​ntawm cov neeg mob hemodialysis (HD) tau txais kev kho ESA [2].

ESA hyporesponsiveness tseem yog ib qho teeb meem nyuaj hauv kev kho mob. Tam sim no, tsis muaj cov txheej txheem thoob ntiaj teb txhais los txhais ESA hyporesponsiveness. Txij li tsis muaj kev sib koom ua ke txhais tau txiav txim siab, qhov tshaj tawm tshaj tawm ntawm ESA hyporesponsiveness txawv raws li kev txhais tau siv. ESA hyporesponsiveness portrays phem prognosis [3]. Kev nce ESA koob tshuaj kom ua tiav hemoglobin (HgB) lub hom phiaj tuaj yeem ua rau cov hlab plawv, thrombotic, thiab kev pheej hmoo tuag tom ntej [4]. Kev sib raug zoo ntawm ESA koob tshuaj thiab HgB qib tau txais txiaj ntsig ntau ntxiv. Kev tshawb fawb txuas ntxiv nthuav dav rau ntau yam uas cuam tshuam rau qhov kev sib raug zoo thiab tsis muaj kev sib raug zoo. Hlau deficiency, o, thiab lub luag hauj lwm ntawm hepcidin nyob rau hauv cov txheej txheem no yog ib tug tsis ntev los no lub ntsiab lus ntawm kev txaus siab nyob rau hauv cov ntaub ntawv hais txog ESA hyporesponsiveness [5, 6]. Lwm yam xws li uremia, CKDmineral pob txha kab mob (CKD-MBD), thiab tsis muaj hlau tsis txaus noj kuj tau kawm ntxiv [7, 8].

Kev txheeb xyuas cov xwm txheej thiab kho cov laj thawj rov qab yuav tsum tau pib ua raws thaum tswj ESA hyporesponsiveness [9]. Qhov kev txiav txim siab, seb puas yuav txuas ntxiv ESA kev kho mob, hinges ntawm cov tsos mob ntawm kev tswj ntshav qab zib, morbidity, lub neej zoo, thiab lub sijhawm yav tom ntej rau kev hloov lub raum [9]. Xyoo kaum xyoo dhau los tau dhau los nrog kev tsim kho tshiab los tswj ntshav ntshav hauv CKD suav nrog kev ua tiav kev lim ntshav txaus hauv HD cov neeg mob los ntawm cov kab mob HD, vitamin E-bonded dialysis membrane daim ntawv thov, thiab lwm txoj hauv kev los txhim kho membrane permeability [10–12]. Kev loj hlob ntawm hypoxia-inducible factor (HIF) prolyl-hydroxylase inhibitors (HIF-stabilizers), tam sim no nyob rau hauv theem III kev soj ntsuam, tso cai rau endogenous zus tau tej cov erythropoietin [13-15]. Kev tswj hwm qhov ncauj, cov txiaj ntsig zoo ntawm HIF stabilizers los tswj ntshav qab zib hauv CKD yog pom tseeb [16]. Muaj kev txhawj xeeb txog cov teebmeem carcinogenic ntawm HIF stabilizers, txawm li cas los xij, thiab nws tseem yuav pom tias lawv puas yog qhov kev daws teeb meem zoo rau lub sijhawm ntev [17].

Hauv qhov kev tshuaj xyuas no, peb yuav rov hais dua cov ntsiab lus tshiab thiab nthuav dav ntawm ESA hyporesponsiveness hauv CKD thiab cov kev sib cav nyob ib puag ncig. Cov pov thawj tsis ntev los no hais txog qhov tshwm sim ntawm kev kho mob ntawm ESA hyporesponsiveness yuav raug tshuaj xyuas. Peb qhov kev nkag siab zaum kawg ntawm yam uas ua rau ESA hyporesponsiveness yuav raug tham, thiab cov txheej txheem ntawm cov xwm txheej no yuav raug tshawb nrhiav. Peb yuav soj ntsuam txoj hauv kev los kho ntshav ntshav hauv CKD thiab yuav ua li cas ESA hyporesponsiveness yuav txo qis. Raws li cov ntaub ntawv pov thawj tam sim no, peb tsom mus txuas ib txoj hauv kev los daws ESA hyporesponsiveness hauv kev tswj lub raum anemia thiab txheeb xyuas qhov seem seem hauv peb lub hauv paus kev paub uas yuav muab cov kev tshawb fawb yav tom ntej.

Herba Cistanche

Txhais ESA Hyporesponsiveness hauv CKD

Tsis muaj kev pom zoo txhais rau ESA hyporesponsiveness thoob ntiaj teb. Nyob rau hauv cov kev hloov kho European Qhov Zoo Tshaj Plaws Cov Lus Qhia (ERBG) 2004, kev soj ntsuam ntawm ESA hyporesponsiveness hauv cov neeg mob CKD tau pom zoo yog tias muaj qhov nce ntawm erythropoietin koob ntau dua lossis sib npaug li 25 feem pua ​​​​kom tswj tau qib HgB tib yam lossis<1 mg/dL gain in HgB after 2–4 weeks [18]. The Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines defined initial ESA hyporesponsiveness as having no increase in HgB concentration from baseline after the first month of treatment on appropriate weight-based dosing [19]. For CKD patients receiving consistent doses of ESA treatment initially, subsequent ESA hyporesponsiveness is defined as those requiring 2 instances of increased ESA doses up to 50% beyond the dose at which they had been stable to maintain similar HgB concentration levels [19]. The Kidney Disease Outcomes Quality Initiative/National Kidney Foundation and Kidney Health Australia-Caring for Australasians with Renal Impairment guidelines currently recommend KDIGO 2012 definition for ESA unresponsiveness [20, 21]. Updated definitions of ESA hyporesponsiveness in select guidelines are summarized in Table 1 [18–23].

Ib qho kev ntsuas ntau ntawm ESA hyporesponsiveness tsim nyob rau hauv 15 xyoo dhau los yog ESA resistance index (ERI). ERI yog raws li qhov sib piv ntawm ESA koob tshuaj ib kilogram thiab HgB qib raws li qhov nruab nrab txhua lub lim tiam [24]. Nws raug nquahu kom ua lub luag haujlwm hauv kev kwv yees qhov tshwm sim thiab ESA cov lus qhia noj [3, 25]. Txawm li cas los xij, qhov siv tau ntawm ERI tseem muaj teeb meem, thiab ERI tseem tsis tau tawm tswv yim rau kev siv hauv kev kho mob los ntawm feem ntau cov lus qhia [24].

Prevalence ntawm ESA Hyporesponsiveness hauv CKD

Cov ntaub ntawv sau npe hauv tebchaws qhia txog qhov muaj feem ntau ntawm ESA hyporesponsiveness tam sim no tsis muaj. Anemia yuav tsum tau pom ntau zaus hauv kev lim ntshav ntau dua li cov neeg mob uas tsis yog CKD. Hauv kev soj ntsuam kev tshawb fawb suav nrog HD thiab peritoneal dialysis cov neeg mob, Bae li al. [26] muab faib ERI rau hauv cov tertiles los sawv cev rau qib ntawm ESA teb thiab tau sau tseg 33 feem pua ​​​​ntawm HD lossis peritoneal dialysis cov neeg mob tau muab cais ua cov tertile siab tshaj plaws, qhov siab tshaj plaws tertile sawv cev rau cov neeg mob uas tsis zoo ESA teb. Los ntawm lwm cov kev tshawb fawb cohort feem ntau tsom rau HD pawg, ESA hyporesponsiveness txawv ntawm 5 thiab 20 feem pua ​​​​hauv HD cov pej xeem [27, 28]. Minutolo et al. [29] tau ua qhov kev soj ntsuam yav tom ntej los ntsuas ESA hyporesponsiveness nyob rau hauv nondialysis CKD cov neeg mob tshaj 4 xyoo los ntawm kev faib ESA teb rau hauv zoo, nruab nrab, thiab pluag pawg, thiab pom 34 feem pua ​​ntawm cov kev tshawb fawb cohorts tau muab tso rau hauv cov neeg pluag ESA teb.

Haiv neeg tau raug sau tseg tias yog ib qho kev pheej hmoo rau ESA tsis teb rau hauv kev tshawb fawb soj ntsuam ntawm 20,516 tus neeg mob tau txais HD los ntawm Okoro li al. [30] txawm tias lub koom haum no tsis tseem ceeb thaum noj hnub nyoog, poj niam txiv neej, thiab kev lim ntshav vintage rau hauv tus account hauv ntau hom qauv. Kev ua hauj lwm ntxiv yog yuav tsum tau soj ntsuam ESA hyporesponsiveness thoob plaws ntau yam kev noj qab haus huv thoob ntiaj teb thiab kev cuam tshuam ntawm kev lag luam hauv zej zog rau qhov no.

Kev kho qhov tseem ceeb ntawm ESA Hyporesponsiveness hauv CKD

Tshaj li kaum xyoo dhau los, cov txiaj ntsig kho mob ntawm ESA hyporesponsiveness tau tshawb xyuas nrog ntau zaus. Cov txiaj ntsig hauv HD cov neeg mob tau nyiam cov kev tshawb fawb tshaj plaws [3, 31, 32]. Hauv kev tshawb fawb soj ntsuam ESA koob tshuaj thiab kev teb rau cov xwm txheej sib xyaw raws li tau hais los ntawm cov xwm txheej hauv plawv, kev kis mob, tsev kho mob, thiab kev tuag, Kuragano li al. [31] tau pom tias qhov siab ESA ntau npaum li cas thiab qhov tsis txaus siab yog cuam tshuam rau qhov tshwm sim ntawm qhov tshwm sim tsis zoo, ntawm 1,095 kev saib xyuas HD cov neeg mob ua raws li 2 xyoos. Txoj kev tshawb fawb "RISchio CARdiovascolare nei pazienti afferent all'Area Vasta In Dialis" (RISCAVID) tau tshawb xyuas 753 tus neeg mob ntawm kev saib xyuas HD dhau 36 lub hlis uas cov ntaub ntawv pej xeem, chaw kho mob, thiab chaw kuaj mob; comorbidity tej yam kev mob; muab tshuaj; tag nrho-ua rau tuag; thiab cov xwm txheej tuag taus thiab tsis tuag taus tau kaw [33]. Cov kws tshawb nrhiav tau ntsuas ERI, C-reactive protein (CRP), thiab interleukin -6 (IL-6) hauv cov neeg mob kawm. Nrog ERI qhov tseem ceeb categorized hauv quartiles (quartile I<5.6, quartile II 5.7–9.6, quartile III 9.7–15.4, and quartile IV >15.4), ERI tau pom muaj kev sib raug zoo nrog tag nrho cov neeg tuag nrog rau cov xwm txheej mob plawv thiab tsis tuag (RR 1.97, 95 feem pua ​​​​CI 1.39–2.79 thiab RR 1.62, 95 feem pua ​​​​CI 1.12–2.33, raws li txoj kev tshawb fawb) ]. Tsis tas li ntawd, cov qib CRP tau siab dua rau cov neeg mob uas muaj qhov siab tshaj plaws quartile ntawm ESA hyporesponsiveness, piv txwv li, quartile IV (p < 0.001), thiab kwv yees tag nrho-ua rau kev tuag thiab mob plawv [33]. Hauv kev tshawb fawb RISCAVID, IL-6 tau pom tias yog ib qho kev kwv yees ntawm ESA hyporesponsiveness; Txawm li cas los xij, qhov no tsis yog rau CRP [33].

Kev sib koom ua ke ntawm ESA hyporesponsiveness thiab thawj zaug thrombotic xwm txheej tau siv dav hauv HD cov neeg mob [3, 32, 34]. Cov ntaub ntawv tsis ntev los no kuj tau hais txog qhov nce nqi kho mob cuam tshuam nrog cov txiaj ntsig kho mob tsis zoo hauv ESA hyporesponsiveness [35].

Cov kev tshawb fawb soj ntsuam tham txog qhov tshwm sim tsis zoo hauv ESA hyporesponsiveness rau cov tsis-HD CKD pawg tseem txwv [36]. Cov pov thawj nyuaj uas qhia txog kev sib koom ua ke ntawm ESA hyporesponsiveness thiab lwm yam tshwm sim, xws li lub raum ua haujlwm trajectory, tsis tshua muaj. Lub hom phiaj yav tom ntej los daws cov kev tshawb fawb no yuav tsum koom nrog ntau tus neeg mob CKD uas tau txais ntau hom kev kho mob raum.

Factors Associated nrog ESA Hyporesponsiveness hauv CKD

Cov ntsiab lus ntawm cov kev paub tam sim no cuam tshuam nrog ESA hyporesponsiveness hauv CKD thiab lawv cov kev kho mob teb tau qhia hauv Table 2.

1. Hlau Deficiency

Hlau deficiency yog feem ntau ua rau ESA hyporesponsiveness nyob rau hauv CKD, nrog erythropoiesis yog thawj neeg siv hlau nyob rau hauv tib neeg lub cev. Cov biomarkers tseem ceeb ntawm cov xwm txheej hlau yog cov ntshav ferritin thiab transferrin. Ferritin qhia txog lub cev cov hlau cia, tab sis tej zaum yuav tsis muaj tseeb nyob rau hauv lub xeev inflammatory vim nws cov theem protein profile. Nws tuaj yeem raug tsa hauv cov neeg mob uas tsis muaj hlau tsis muaj ntshav liab thaum muaj kab mob siab ua ke lossis mob qog nqaij hlav [37]. Transferrin yog plasma protein uas thauj cov hlau hla cov hlab ntshav rau kev siv thiab yog qhov qhia txog kev ua haujlwm muaj hlau. Transferrin qib poob hauv cov hlau tsis muaj peev xwm [37].

Tsis muaj hlau tsis txaus yog txhais los ntawm qhov txo qis transferrin saturation (TSAT) qib tsawg dua lossis sib npaug li 20 feem pua, thiab cov ntshav ferritin concentration tsawg dua lossis sib npaug li 100 ng / mL rau kev lim ntshav ua ntej thiab cov neeg mob ntshav qab zib peritoneal lossis tsawg dua lossis sib npaug. rau 200 ng / mL rau cov neeg mob HD [37, 38]. Cov ntshav poob, xws li plab hnyuv los ntshav thiab kev coj khaub ncaws ntau dhau, ua rau muaj kev xav tau hlau ntxiv [39]. Tsis muaj hlau tsis txaus yog tshwm sim los ntawm kev nqus tsis txaus ntawm plab hnyuv cuam tshuam txog kev mob xws li mob plab hnyuv thiab kab mob celiac [39]. Kev noj zaub mov tsis txaus yog nquag pom hauv CKD. Kev noj zaub mov tsis zoo thiab kev haus cawv ntev ntev kuj tseem ua rau muaj qhov tsis txaus ntawm cov hlau tsis txaus [40].

Functional iron deficiency is currently defined by ferritin concentration >100 ng/ml TSAT<20% [37, 38]. Despite adequate iron stores overall, anemia develops because of inefficient iron utilization [37]. Anemia of chronic disease is the most well-known cause [37, 38]. Erythrocytes may appear normocytic or microcytic [38]. Inflammation and the role of hepcidin in functional iron deficiency will be discussed in the next subsections.

2. Mob

Kev ua xua yog ib qho tseem ceeb hauv ESA hyporesponsiveness thiab cuam tshuam cov txiaj ntsig kho mob [41]. Nyob nruab nrab ntawm 30 thiab 50 feem pua ​​​​ntawm cov neeg mob HD tau pom tias muaj qib CRP thiab IL-6 nce, txawm tias tsis muaj peev xwm txheeb xyuas qhov mob lossis kis kab mob. Kev mob tshwm sim hauv uremia tuaj yeem yog episodic lossis mob ntev tab sis cuam tshuam nrog kev ua rau tag nrho cov neeg tuag [42]. Ua rau o zoo li multifactorial. Cov kev ntxhov siab ntawm lub raum tsis zoo yog sib xyaw ua ke los ntawm comorbidities, nce oxidative kev nyuaj siab thiab kev pheej hmoo kis mob, rog rog, thiab caj ces thiab kev tiv thaiv kab mob [6, 42, 43]. Rau cov neeg mob tau txais kev lim ntshav, lim ntshav tsis txaus sau cov cytokines inflammatory [44]. Catheter thiab graft access infections ntxiv inflammatory kev pheej hmoo [45]. Cov txheej txheem ntawm yuav ua li cas o tshwm sim hauv CKD yuav muaj feem cuam tshuam rau lub raum tshem tawm ntawm cov qog necrosis factor- , interleukin -1, thiab IL-6, ntawm lwm cov pro-inflammatory cytokines [6, 46]. Kev tsim tawm ntau ntxiv ntawm cov cytokines yuav tsum tau [6, 46]. Kev ua kom muaj zog ntawm cytokines hauv uremia feem ntau tshwm sim los ntawm kev txo qis ntawm cov enzymes antioxidant, superoxide dismutase, thiab glutathione peroxidase [47]. Cov txheej txheem pathophysiological ntawm cov txheej txheem no tsis meej meej thiab lav kev tshawb nrhiav ntxiv. Dab tsi yog paub yog tias inflammatory cytokines ncaj qha inhibit erythropoiesis thiab txhawb apoptosis ntawm erythroid precursors [6, 46].

3. Hepcidin

Hepcidin yog cysteine-nplua nuj, 25-amino acid peptide hormone [48]. Nws lub luag haujlwm tseem ceeb yog txhawm rau tiv thaiv cov hlau nkag mus rau hauv cov ntshav los ntawm cov cellular ib puag ncig [49, 50]. Hepcidin txo cov hlau nyob hauv tib neeg lub cev los ntawm kev khi rau ferroportin, lub cellular hlau thauj khoom uas xa tawm cov hlau nqus los ntawm duodenal enterocytes, rov siv hlau los ntawm splenic thiab hepatic macrophages, thiab khaws cov hlau los ntawm hepatocytes rau plasma [49, 50]. Ua kom cov ntshav hepcidin nce qhov zaus ntawm hepcidin-ferroportin khi, thiab yog li ntawd ntau dua inhibition ntawm hlau efflux [49, 50]. Direct hepcidin-ferroportin binding ua rau endocytosis hauv ob qho tib si molecules, yog li ua rau lysosomal degradation [49, 50].

Hepatocytes yog qhov chaw tseem ceeb ntawm hepcidin ntau lawm txawm tias lwm hom cell xws li macrophages thiab adipocytes kuj qhia hepcidin mRNA [51]. Kev tshawb fawb tsis tu ncua txuas ntxiv tshawb nrhiav qhov chaw ntawm kev tsim cov hepatic hepcidin. Hepcidin synthesis yog txhawb los ntawm qhov sib txawv ntawm cov ntshav plasma transferrin thiab khaws cia hlau hauv hepatocytes [50]. Kev tsim tawm Hepcidin feem ntau yog tswj hwm los ntawm cov lus qhia tawm tswv yim uas cuam tshuam txog lub cev muaj zog hlau thiab khaws cia hauv tib neeg lub cev, nrog rau kev ua haujlwm ntawm lub cev erythropoiesis thiab kev tiv thaiv tus tswv [50]. Thaum cov qib hlau muaj ntau, ntau hepcidin raug tsim, thaum hepatocytes tsim cov hepcidin tsawg dua hauv cov hlau tsis muaj zog [50]. Rau qhov tsawg dua, hepcidin ntau lawm yog tswj los ntawm erythropoietic xav tau hlau hauv lub cev [50]. Hepcidin ntau lawm yog suppressed thaum lub sij hawm nquag erythropoiesis, tso cai ntau dua hlau muaj rau HgB synthesis [50]. Txawm hais tias tseem tsis tau piav qhia meej, kev tawm tsam ntawm hepcidin ntau lawm tshwm sim nyob rau hauv cov ntsiab lus no los ntawm erythroid yam, ib qho circulating factor uas tsim los ntawm cov pob txha pob txha erythroid precursors [52]. Daim duab qhia txog kev tswj hwm hepcidin thiab kev ua hauv cov hlau homeostasis yog pom hauv daim duab 1 [53].

Hauv CKD, 2 lub tswv yim tseem ceeb - ua rau lub raum tsis zoo thiab ua rau muaj kev kub ntxhov - ua rau kom cov ntshav siab hepcidin ntau ntau [52]. Rau lub raum ua haujlwm zoo, hepcidin yooj yim dhau los ntawm glomerular membrane qhov twg nws tau coj mus thiab degraded nyob rau hauv cov tubule proximal, zoo ib yam li lwm cov proteins me me. Cov feem me me ntawm lim hepcidin yuav dhau mus rau hauv cov zis uas nws nkag tau yooj yim [54]. CKD impairs hepcidin clearance thiab ua rau nws tsub zuj zuj hauv plasma [54]. Txawm hais tias muaj cov lus qhia tias cov ntshav hepcidin tuaj yeem sib txuas nrog 2-microglobulin, nws txoj kev sib raug zoo rau hepcidin yog qis, thiab feem ntau ntawm cov ntshav hepcidin yuav tsis muaj kev cuam tshuam [55]. Cov ntshav siab hepcidin txwv tsis pub muaj hlau rau erythropoiesis, ua rau ESA hyporesponsiveness.

Cov theem transcriptional ntawm hepcidin synthesis los ntawm hepatocytes yog tswj los ntawm IL-6 los ntawm STAT-3 signaling pathway [56]. Vim li no, nce hepcidin ntau lawm tau pom thaum lub sij hawm mob hnyav ntawm kev kis kab mob thiab kab mob hauv lub cev. Piv nrog rau lwm yam hepcidin-inducing mechanisms uas txo cov hlau muaj, mob hnyav, thiab o tuaj yeem txo cov qib hlau ntawm qhov ceev tshaj plaws [52]. Tus tswv tsev tiv thaiv mechanism uas muaj cov txheej txheem sib npaug ntawm cov hlau-dependent extracellular microbes raug txwv los ntawm lub cev cov khoom siv hlau [52]. Lub downside ntawm no mechanism yog nce hlau sequestration nyob rau hauv teb. Kev ua kom lub cev reticuloendothelial thiab nce hepcidin ntau lawm yuav txwv qhov muaj peev xwm ntawm erythropoiesis [52]. Anemia ntawm o (kab mob ntev) ua rau kev ua haujlwm tsis muaj hlau thiab ESA hyporesponsiveness hauv CKD.

Ntau qhov kev tshawb fawb tau pom tias muaj peev xwm kuaj tau ntawm cov ntshav hepcidin rau ESA hyporesponsiveness hauv ob qho tib si lim ntshav thiab nondialysis CKD cov neeg mob [5, 6]. Kev sib raug zoo tam sim no ntawm cov ntshav hepcidin qib thiab ESA hyporesponsiveness tseem xav tau kev soj ntsuam ntxiv thiab kev tshawb fawb yav tom ntej tau lees paub los daws qhov no.

4. CKD-Mineral Bone Disease

CKD-MBD yog ib qho kev tshwm sim ntawm CKD thiab ib qho kev lees paub ntawm ESA hyporesponsiveness. Kev sib txuas ntawm cov vitamin D tsis muaj peev xwm, theem nrab hyperparathyroidism, thiab ESA hyporesponsiveness tau tsim tau zoo [57].

Qhov tsis muaj peev xwm los tsim cov vitamin D (1,25 (OH2) D3) los ntawm nws daim ntawv tsis muaj zog 25 (OH2) D3 yog qhov ua rau muaj vitamin D tsis txaus hauv CKD [58]. Qhov no yog exacerbated los ntawm kev noj zaub mov tsis txaus, raug tshav ntuj tsis zoo, thiab nephrotic urinary poob [58]. Cov haujlwm pleiotropic ntawm vitamin D koom nrog cov kab ke hematopoietic, uas piav qhia lub luag haujlwm ntawm vitamin D tsis txaus hauv ESA hyporesponsiveness [8, 58]. 1,25 (OH2) D3 khi rau cov vitamin D receptor los siv nws cov teebmeem ntawm erythropoiesis [8].

Nce parathyroid hormone (PTH) ncig los ntawm theem nrab hyperparathyroidism yog ib qho ntawm ESA hyporesponsiveness [57, 59]. PTH ncaj qha inhibits erythroid progenitors thaum ntxov thiab txo cov endogenous erythropoiesis thiab liab cell ciaj sia [59]. Metabolic acidosis thiab hyperphosphatemia cuam tshuam nrog hyperparathyroidism theem nrab txhawb txoj kev hloov pauv ntawm oxygen dissociation nkhaus thiab downregulation ntawm erythropoietin receptors [59]. Tshaj uremic thiab inflammatory load exacerbates lub xeev hyperparathyroid los ntawm calcium-dependent thiab calcium-ywj siab mechanisms [59]. Kev hloov pauv kev loj hlob zoo- thiab zoo li insulin-zoo li kev loj hlob zoo li -1 receptor downregulation yog exacerbated nrog rau theem nrab hyperparathyroidism nyob rau hauv cov neeg mob uas muaj mob uremic xeev, yog li ua rau lub nra ntawm ESA hyporesponsiveness [59]. Pob txha pob txha fibrosis, ib qho teeb meem ntawm theem nrab hyperparathyroidism, tau tshaj tawm cov koom haum nrog ESA hyporesponsiveness [57, 59].

Nyob rau hauv xyoo tas los no, fibroblast kev loj hlob zoo tshaj -23 (FGF-23) thiab alkaline phosphatase tau tawm tswv yim ua biomarkers los cuam tshuam ESA hyporesponsiveness xwm txheej; Txawm li cas los xij, yuav tsum muaj kev ntsuam xyuas ntau dua [60, 61]. FGF-23 yav dhau los tau pom tias yog tus tswj tsis zoo ntawm erythropoiesis hauv nas [60]. Txawm hais tias cov hlau txwv erythropoiesis tsis tu ncua txhim kho nrog kev txo qis ntawm FGF-23 qib hauv CKD yuav tsum muaj kev lees paub ntxiv [62].

5. Kev tsis muaj hlau tsis zoo

Qhov cuam tshuam ntawm kev noj zaub mov tsis muaj hlau ntawm ESA hyporesponsiveness yuav tsum tsis txhob kwv yees. Folic acid yog qhov tseem ceeb los txhawb cov txheej txheem koom nrog hauv erythroid proliferation, xws li nucleotide synthesis, kho DNA, thiab homocysteine ​​re-methylation [63]. Vitamin C txhawb nqa kev nqus hlau thiab siv los ntawm cov khw muag ntaub so ntswg thiab downregulates cytokine synthesis los ntawm hepatocytes los ntawm nws lub luag hauj lwm raws li ib tug antioxidative tsis muaj oxygen scavenger [64]. Tooj liab txhawb kev nqus hlau los ntawm txoj hnyuv [65]. Ob leeg-lipoic acid thiab L-carnitine ua si lub luag haujlwm txhawm rau txo qhov mob [66, 67]. -Lipoic acid, xav tau rau ATP synthesis, txo oxidative kev nyuaj siab los ntawm kev txo cov ntshav concentration ntawm symmetric-dimethyl arginine [66]. L-Carnitine txhawb nqa heme-oxygenase 1, uas muaj cov teebmeem antioxidant, thiab sib koom tib txoj kev metabolic nrog erythropoietin [67]. Protein-zog nkim thiab vitamin B12 tsis muaj peev xwm yav dhau los tau pom tias muaj kev koom tes nrog ntshav ntshav thiab ESA hyporesponsiveness [42, 68]. Cov txiaj ntsig tsis sib haum xeeb tau piav qhia txog kev sib raug zoo ntawm vitamin B6 thiab ESA hyporesponsiveness [69]. Cov txheej txheem ntawm cov koom haum no xav tau kev tshawb nrhiav ntxiv.

6. Lwm yam

Angiotensin-hloov enzyme inhibitors thiab angiotensin-receptor blockers txhawb ESA hyporesponsiveness los ntawm ntau lub tswv yim, uas inhibition ntawm angiotensin-II-induced erythropoietin tso tawm thiab augmentation ntawm N-acetyl-seryl-aspartyl-lysyl-proline los tiv thaiv kev nrhiav neeg ntawm pluripotent hematopoietic hlwb. yog cov mechanisms loj [70]. Cov neeg mob uas mob qog noj ntshav, nrog lossis tsis muaj CKD, feem ntau ua rau ESA hyporesponsiveness [71]. Qhov no feem ntau pom nyob rau hauv cov neeg mob uas muaj hematological malignancies xws li ntau yam myeloma thiab chronic lymphocytic leukemia [71]. ESA hyporesponsiveness tau pom tias koom nrog cov kab mob hauv cov pob txha hauv nruab nrab thiab theem nrab rau cov neeg ua haujlwm myelosuppressive; Txawm li cas los xij, qhov no tsis tshua muaj [72]. Antibody-mediated pure red cell aplasia los ntawm kev tsim tawm ntawm neutralizing anti-ESA cov tshuaj tiv thaiv thaum lub sij hawm ESA tswj tsis tshua muaj [73]. ESA hyporesponsiveness stemming los ntawm txhuas overload vim distortion nyob rau hauv cov txheej txheem koom nrog hauv heme synthesis yog tsis tshua muaj qhia [74].

Cistanche capsules

Kev tswj ntawm ESA Hyporesponsiveness thiab Anemia hauv CKD

1. Hlau ntxiv

Tsis muaj kev taw qhia meej rau kev pom zoo hlau ntxiv rau hauv CKD. KDIGO 2012 pom zoo kom cov hlau repletion yog TSAT Tsawg dua lossis sib npaug li 30 feem pua ​​thiab cov ntshav ferritin tsawg dua lossis sib npaug li 500 ng / mL [19]. ERBG 2013 pom zoo cov hlau repletion tsuas yog TSAT<20% and serum ferritin <100 ng/mL, with aims to remain at TSAT ≤30% and serum ferritin ≤500 ng/mL [1]. More recent results show high proportions of CKD patients with ferritin ≥500 ng/mL [75]. NICE 2015 and BRA 2017 advised ferritin cutoffs of 800 ng/mL for patients receiving iron supplementation [22, 23].

Kev npaj ferrous ntawm qhov ncauj tswj hwm cov hlau feem ntau siv vim yog tus nqi thiab muaj [76]. Rau cov neeg mob CKD uas xav tau IV hlau, koob tshuaj me me thiab ntau zaus ntawm kev tswj hwm raug pom zoo los txhim kho tus nqi-txheej txheem ntawm cov hlau txwv erythropoiesis [76].

Ferritin qib hauv cov hlau ntxiv yog nruj saib xyuas vim muaj kev ntshai ntawm cov hlau overload [76]. Kev txhawj xeeb cuam tshuam txog kev puas tsuaj los ntawm oxidative kev nyuaj siab, muaj kev pheej hmoo ntawm kev kis kab mob, atherosclerosis, thiab cov ntaub so ntswg-hlau deposition [76]. Muaj ntau cov pov thawj los txhawb ntau txoj kev ywj pheej ntawm kev siv hlau ntxiv, raws li tau pom los ntawm cov txiaj ntsig hauv PIVOTAL randomized-tswj kev sim sib piv cov koob tshuaj siab thiab cov tshuaj tiv thaiv qis IV hlau ntxiv hauv HD cov neeg mob [77]. Nrog lub qab nthab ntawm ferritin<700 ng/mL and TSAT <40%, the high-dose arm demonstrated lower mortality, cardiovascular events, and hospitalization after 2 years of follow-up, with lower ESA and transfusion requirements [77].

Tsis muaj hlau tsis muaj peev xwm tuaj yeem tswj tau nrog lub qhov ncauj lossis IV hlau, thaum ua haujlwm tsis muaj hlau yuav xav tau IV hlau ntxiv vim tias tsis zoo ntawm cov hnyuv thiab siv cov khw muag khoom hlau [37, 38]. Ntau qhov kev sim siab xws li REVOKE thiab FIND-CKD tau soj ntsuam qhov kev pheej hmoo- txiaj ntsig zoo rau IV hlau piv rau kev siv hlau hauv qhov ncauj, uas pom cov txiaj ntsig sib xyaw [78, 79].

2. HIF-Stabilizers

Txij li thaum tshawb pom HIF rau EPO noob hauv xyoo 1992, kev txhim kho cov tshuaj, hu ua HIF-stabilizers lossis prolyl hydroxylase domain (Ph.D.) inhibitors, ua los ntawm HIF-PHD txoj hauv kev tau coj txoj hauv kev tshiab rau kev tswj ntshav qab zib hauv lub raum. . Erythropoiesis nyob rau hauv HIF-PHD yog nyob ntawm hypoxic xwm txheej nyob rau hauv cellular ib puag ncig vim oxygen-degradation ntawm HIF tswj nws qib [16]. Hauv CKD qib siab, txo qis oxygen diffusion mus rau hauv lub raum hlwb tshwm sim vim muaj fibrosis ntau ntxiv, nrog rau kev hloov pauv ntawm erythropoietin-ua hlwb rau hauv lub raum myofibroblasts [80]. Hypoxia yog exacerbated los ntawm lwm yam xws li kev puas tsuaj ntawm peritubular capillary tes hauj lwm, nce metabolic xav tau los ntawm lub raum tubule, thiab txo peritubular capillary ntshav txaus [80].

HIF yog heterodimer ua los ntawm thiab subunits [80]. Muaj 3 isoforms ntawm lub subunit: HIF-1 , HIF-2 , thiab HIF-3 uas txhua tus tuaj yeem ua ke nrog lub subunit los txhawb kev qhia ntawm cov hom phiaj sib txawv ntawm cov noob sib txawv [80]. Kev tswj hwm kev ua haujlwm HIF tshwm sim nrog HIF-subunit, ua ke tsis tu ncua hauv cov hlwb, ua rau hydroxylation ntawm cov khoom tshwj xeeb proline residues [80]. Cov txheej txheem no yog ua tiav los ntawm Ph.D., thiab cov hydroxylated HIF- yog ces ubiquitinated los ntawm von Hippel Lindau-E3 ligase complex ua ntej degradation los ntawm cov proteasome [81]. Thaum Ph.D. kev ua haujlwm txo qis hauv hypoxia, txo hydroxylation ntawm HIF- tso cai rau nws kom ruaj khov thiab hloov mus rau hauv lub nucleus, qhov twg dimerization tshwm sim nrog HIF- [80, 81]. Kev ua kom muaj EPO gene tshwm sim nyob rau hauv lub nucleus tom qab khi rau lub hypoxia teb lub caij (HRE) ntawm lub hom phiaj gene tswj cheeb tsam ntawm lwm cov noob [80, 81]. Nyob rau hauv lub xeev hypoxic, nce stabilization ntawm HIF- yuav nce erythropoiesis kev ua haujlwm pib [80, 81]. Nws thiaj li, HIF muaj nuj nqi thiab kev qhia tsis txaus los tswj cov kev xav tau ntawm erythropoiesis nyob rau hauv ib puag ncig hypoxic, exacerbated los ntawm ntau tshaj oxidative kev nyuaj siab, uremia, thiab inflammatory cytokine ntau lawm.

HIF stabilizers tau ua rau muaj kev cia siab rau qhov teeb meem no los ntawm kev kho erythropoiesis ntawm tus nqi sib xws thiab hais txog ESA hyporesponsiveness. Kev tswj cov hlau homeostasis kom tau raws li cov kev xav tau hlau yog qhov tseem ceeb. Cov cuab yeej koom nrog hauv cov txheej txheem no nce kev hloov pauv, hloov pauv receptor concentration, duodenal cytochrome B, divalent hlau thauj khoom -1, thiab qib ceruloplasmin [82]. Cov teebmeem ntawm HIF-stabilizers hauv kev tawm tsam hepcidin thiab lwm yam pro-inflammatory cytokine ntau lawm tau zoo-validated [16, 83]. Cov koom haum nrog kev noj zaub mov zoo dua qub thiab cov pob txha noj qab haus huv tau pom nyob rau hauv kev sim hais txog HIF stabilizers [83]. Kev txhim kho thiab kev koom ua ke ntawm HIF stabilizers rau hauv kev kho mob tau dhau los ntawm lub zog mus rau lub zog nrog rau feem ntau tau ua tiav, lossis yog nyob rau theem III txuas ntxiv tam sim no [15, 84–87]. Lawv tau nyob rau hauv kev saib xyuas nyob rau hauv kev soj ntsuam tom qab kev ua lag luam nyob rau hauv lub xyoo caum tom ntej, nrog kev pom zoo rau kev siv tshuaj nyob rau hauv Asia-Pacific lub teb chaws xws li Tuam Tshoj thiab Nyiv tam sim no [88]. Nws tseem yuav pom tias HIF stabilizers puas yuav raug pom zoo los ntawm United States Food and Drug Administration, tom qab daim ntawv thov ua tsis tiav rau roxadustat thaum Lub Xya Hli 2021.

Txawm hais tias muaj ntau qhov zoo ntawm HIF stabilizers, kev txhawj xeeb txog cov tshuaj no cuam tshuam nrog lawv cov kev pheej hmoo malignancy. Kev hloov pauv ntawm VEGF noob yog tswj hwm los ntawm HIF-1 thiab HIF-2 khi rau cov ntsiab lus hypoxia teb [17]. Kev pheej hmoo ntawm neoplasia thiab ntshav qab zib retinopathy los ntawm kev siv HIF-stabilizer yuav tsum raug lees paub tias VEGF txhawb nqa angiogenesis, vascular permeability, thiab qog loj hlob [17]. Phase II cov kev tshawb fawb rau vadadustat thiab daprodustat tsis tau pom qhov hloov pauv hauv VEGF qib dhau ntawm cov koob tshuaj uas tau npaj rau theem III kev sim tshuaj [89, 90]. Lwm yam kev phiv xws li metabolic acidosis, hyperkalemia, thiab kab mob ua pa sab sauv tau tshaj tawm hauv ntiaj teb thawj HIF-stabilizer theem III kev sim tshuaj rau roxadustat hauv caj npab kho [15, 86]. Mus rau pem hauv ntej, peb tos ntsoov cov ntsiab lus tseem ceeb ntxiv los txiav txim siab seb HIF-stabilizers yog qhov kev daws teeb meem los daws ESA hyporesponsiveness hauv ntshav ntshav hauv CKD nyob rau lub sijhawm ntev.

Cistanche extract

3. Kev tswj cov kab mob ua paug

Txoj hauv kev ib txwm siv los tswj kev mob hauv CKD yog los kho cov kab mob ua rau, txawm tias yog tshuaj tua kab mob rau tus kab mob hnyav lossis kev kho mob steroid rau cov kab mob ntev. Iron supplementation thiab txaus dialysis nyob rau hauv anemia ntawm o thiab txo hepcidin ntau ntau. Cov kev kho tshiab tshiab tsom rau inhibit hepcidin ntau lawm raug soj ntsuam. Anti-IL-6 thiab IL-6 monoclonal antibody kev kho mob xws li tocilizumab thiab sultuximab yog touted raws li cov kev xaiv muaj peev xwm [91, 92]. Kev siv Atorvastatin hauv CKD tau tham txog kom txo cov ntshav hepcidin qib [93]. Kev tshawb fawb tsis ntev los no kuj tau hais txog kev siv pentoxifylline, ib qho methylxanthine derivative, yuav muaj kev tiv thaiv kab mob thiab txhim kho ESA teb rau CKD cov neeg mob ntshav qab zib [94]. Nyob rau hauv ib qho kev pom zoo ntau yam, pentoxifylline inhibits zus tau tej cov pro-inflammatory cytokines, xws li interleukin -2 thiab interferon-gamma [94].

4. Dialysis txaus

Kev ua kom lub zog ntawm kev lim ntshav thiab dialysate ntws los txo ESA hyporesponsiveness tuaj yeem ua tiav los ntawm ntau lub tshuab. Qhov muaj ntawm convective HD tso cai rau kev tshem tawm ntawm nruab nrab-qhov hnyav molecules, xws li inflammatory cytokines, thiab peptides xws li hepcidin [10]. Txoj kev tshawb REDERT yog ib qho kev sib tw hla kev sib piv piv cov txiaj ntsig hauv cov neeg mob uas tau txais cov ntim hauv online hemodiafiltration nrog high-flux polysulfone membranes thiab pauv ntim 20L / ntu piv rau tus qauv bicarbonate dialysis nrog low-flux polysulfone membranes [10]. Txhim kho ESA teb thiab txo cov ntshav hepcidin qib tau pom nyob rau hauv online hemodiafiltration pab pawg hauv 3- thiab 6- hli rov qab, raws li [10].

Cov kev xaiv los hloov cov membrane permeability thaum lub sij hawm lim ntshav tau nthuav dav nyob rau lub sijhawm tsis ntev los no. Vim muaj cov teebmeem antioxidant ntawm vitamin E, daim ntawv thov ntawm hluavtaws vitamin E-bonded dialysis membranes thaum lub sij hawm lim ntshav tau raug txiav txim siab. Ib tug multicenter, randomized, tswj mus sib hais los ntawm Locatelli li al. [11] tau piav qhia txog kev txhim kho ESA kev teb rau cov neeg mob tau txais HD nrog cov vitamin E-coated polysulfone piv rau cov tshuab hluav taws xob qis qis. Cov pov thawj ntsuas qhov cuam tshuam ntawm daim nyias nyias permeability ntawm ESA cov lus teb feem ntau tseem ntxov ntxov, thiab yuav tsum muaj kev siv tau ntxiv ntawm cov kev ntsuas no.

5. CKD-MBD Management

Kev kho kom zoo CKD-MBD tuaj yeem txhim kho ESA teb rau cov neeg mob nyob nrog CKD. Vitamin D muab tshuaj noj txhua hnub, txhua lub lim tiam, lossis txhua hli yog qhov tseem ceeb raws li kev kho mob tiv thaiv kab mob [95]. Kev siv ntau yam vitamin D analogs thiab vitamin D receptor activators tau pom tias nce hauv ESA teb, tshwj xeeb tshaj yog rau HD pawg [96]. Vitamin D supplementation muaj qhov cuam tshuam ncaj qha rau PTH thiab qib hepcidin qib [97].

KDIGO 2017 cov lus qhia ntawm CKD-MBD pom zoo kev tswj hwm kev kho mob ntawm theem nrab hyperparathyroidism thawj zaug thiab xav txog kev txiav txim siab parathyroidectomy yog tias kev kho mob yog refractory [98]. Cov ntaub ntawv pov thawj tshaj tawm tau txhim kho ESA cov lus teb tom qab parathyroidectomy lossis kho calcimimetic [99, 100]. Txawm hais tias nws muaj peev xwm tau txais txiaj ntsig, muaj kev pheej hmoo ntau ntxiv ntawm kev tuag mob hnyav los ntawm kev phais mob yuav tsum tau lees paub rau cov uas tab tom ua rau parathyroidectomy [99]. Hyperphosphatemia los ntawm theem nrab hyperparathyroidism tau pom tias cuam tshuam nrog ESA hyporesponsiveness; Txawm li cas los xij, lub tshuab yuav tsum tau ntsuas ntau dua [101].

6. Kev tswj tsis muaj hlau tsis txaus

Kev rov qab los kho cov tsis muaj hlau tsis txaus tuaj yeem txhim kho ntshav qab zib hauv CKD thiab ESA cov lus teb. Cov lus qhia tam sim no tsis tawm tswv yim ntxiv txog kev ntxiv cov khoom noj rau cov neeg mob CKD uas tsis muaj txiaj ntsig, vim muaj kev txhawj xeeb txog qib kev nyab xeeb thiab kev pheej hmoo- txiaj ntsig sib npaug. Kev pom zoo rau folic acid, vitamin C, tooj liab, -lipoic acid, L-carnitine, thiab vitamin B6 thiab B12 supplementation tseem xav tau. Cov qauv loj dua randomized, tswj kev sim yuav tsum tau ua los tsim qhov no.

Cistanche tubulosa

Xaus

Peb txoj kev nkag siab txog cov teeb meem nyob ib puag ncig ESA hyporesponsiveness thiab cov kev daws teeb meem tau nthuav dav ntau xyoo dhau los. Txawm hais tias muaj kev txhawj xeeb ntxiv txog qee qhov kev cuam tshuam tsis zoo, HIF stabilizers tiag tiag yuav yog cov qauv los tshem tawm peb cov kev txhawj xeeb ntawm ESA hyporesponsiveness hauv kev tswj lub raum anemia. Daim duab 2 qhia txog peb txoj kev npaj rau kev ntsuam xyuas thiab kev tswj hwm ntawm ESA hyporesponsiveness raws li cov pov thawj tam sim no. Txawm li cas los xij, tseem muaj ntau qhov sib txawv hauv peb lub hauv paus kev paub txog cov ncauj lus no. Lub zej zog nephrology yuav tsum mob siab rau kom ncav cuag qhov kev pom zoo dav dua txog lub ntsiab lus, kev ntsuam xyuas, thiab kev tswj hwm ntawm ESA hyporesponsiveness los ntawm kev tshawb fawb txuas ntxiv los txiav txim siab txoj hauv kev kub. Lub neej yav tom ntej zoo siab tos txais los daws qhov teeb meem no.

Cov ntaub ntawv

1 Locatelli F, Bárány P, Covic A, De Francisco A, Del Vecchio L, Goldsmith D, thiab al. ERA-EDTA ERBP pawg thawj coj saib xyuas. Kab mob raum: txhim kho cov txiaj ntsig thoob ntiaj teb cov lus qhia txog kev tswj ntshav qab zib hauv cov kab mob raum ntev: European lub raum ua haujlwm zoo tshaj plaws nqe lus. Nephrol Dial Hloov. 2013 Lub Rau Hli; 28(6): 1346–59.

2 United States Renal Data System. Daim ntawv tshaj tawm cov ntaub ntawv txhua xyoo: atlas ntawm cov kab mob raum ntev thiab cov kab mob raum kawg hauv Tebchaws Meskas, lub koom haum National Health, National Institute of Diabetes thiab Digestive thiab raum kab mob. MD, Bethesda; 2020.

3 Hayashi T, Joki N, Tanaka Y, Iwasaki M, Kubo S, Matsukane A, et al. Kev tiv thaiv rau erythropoiesis-stimulating cov neeg ua haujlwm hauv pre-dialysis thiab post-dialysis mortality hauv Japanese xwm txheej hemodialysis cov neeg mob. Ntshav Purif. Peb Hlis 2019; 47(2:31-7.

4 Pérez-García R, Varas J, Cives A, Martín-Malo A, Aljama P, Ramos R, et al. Kev tuag ntau ntxiv hauv cov neeg mob hemodialysis tau siv tshuaj ntau ntawm erythropoiesis-stimulating cov neeg ua haujlwm: kev txheeb xyuas cov qhab nia sib luag. Nephrol Dial Hloov. Lub Plaub Hlis 2018; 33(4): 690–9.

5. Lee SW, Kim HJ, Kim SY, Kim SW, Kim SW, et al. Serum hepcidin tej zaum yuav yog ib qho tshiab uremic toxin, uas tej zaum yuav muaj feem xyuam rau erythropoietin tsis kam. Sci Rep. 2017 Lub Rau Hli; 7(1): 1–8.

6 El Sewefy DA, Farweez BA, Behairy MA, Yassin NR. Kev cuam tshuam ntawm cov ntshav hepcidin thiab cov cim inflammatory ntawm kev tiv thaiv erythropoiesis-stimulating txoj kev kho hauv cov neeg mob hemodialysis. Urol Nephrol Cov. 2019 Lub Ob Hlis; 51(2): 325–34.

7 Rosati A, Ravaglia F, Panichi V. Txhim kho erythropoiesis-stimulating agent hyporesponsiveness nyob rau hauv cov neeg mob hemodialysis: lub luag hauj lwm ntawm hepcidin thiab hemodiafiltration online. Ntshav Purif. 2018 Plaub Hlis Ntuj; 45(1–3): 139–46.

8 Icardi A, Paoletti E, De Nicola L, Mazzaferro S, Russo R, Cozzolino M. Renal anemia thiab EPO hyporesponsiveness txuam nrog vitamin D deficiency: lub luag hauj lwm ntawm o. Nephrol Dial Hloov. 2013 Jul; 28(7): 1672–9.

9 Fishbane S, Spinowitz B. Hloov tshiab ntawm anemia hauv ESRD thiab theem ua ntej ntawm CKD: core curriculum 2018. Am J Kidney Dis. 2018 Peb Hlis; 71(3): 423–35.

10 Panichi V, Scatena A, Rosati A, Giusti R, Ferro G, Malagnino E, et al. High-volume online haemodiafiltration txhim kho erythropoiesis-stimulating agent (ESA) tsis kam nyob rau hauv kev sib piv nrog low-flux bicarbonate dialysis: cov txiaj ntsig ntawm REDERT txoj kev tshawb fawb. Nephrol Dial Hloov. Peb Hlis 2015; 30(4): 682–9.

11 Locatelli F, Andrulli S, Viganò SM, Concetti M, Urbini S, Giacchino F, et al. Kev ntsuam xyuas ntawm qhov cuam tshuam ntawm ib qho tshiab hluavtaws vitamin Ebonded membrane ntawm hypo-responsiveness rau erythropoietin therapy nyob rau hauv cov neeg mob hemodialysis: ib tug multicenter txoj kev tshawb no. Ntshav Purif. Lub Plaub Hlis 2017; 43(4): 338–45.

12 D'Arrigo G, Baggetta R, Tripepi G, Galli F, Bolignano D. Cov teebmeem ntawm cov vitamin E-coated piv rau cov pa membranes hauv cov neeg mob hemodialysis ntev: kev tshuaj xyuas thiab kev tshuaj xyuas meta. Ntshav Purif. Peb Hlis 2017; 43(1–3): 101–22.

13 Cizman B, Sykes AP, Paul G, Zeig S, Cobitz AR. Kev tshawb nrhiav ntawm daprodustat hauv erythropoietin-hyporesponsive kev kawm. Raum Int Rep. 2018 Jul;3(4):841–50.

14 Haase VH, Chertow GM, Block GA, Pergola PE, de Goma EM, Khawaja Z, et al. Kev cuam tshuam ntawm vadadustat ntawm hemoglobin concentration hauv cov neeg mob tau txais hemodialysis yav dhau los kho nrog erythropoiesis-stimulating agents. Nephrol Dial Hloov. 2019 Lub Ib Hlis; 34(1):90–9.

15 Chen N, Hao C, Liu BC, Lin H, Wang C, Xing C, et al. Kev kho mob Roxadustat rau ntshav qab zib hauv cov neeg mob uas tau lim ntshav mus ntev. N Engl J Med. 2019 Sep; 381(11):1011–22.

16 Nair S, Trivedi M. Kev tswj ntshav qab zib hauv cov neeg mob lim ntshav: PIVOT thiab txoj hauv kev tshiab? Curr Opin Nephrol Hypertens Cov. Peb Hlis 29, 2020: 351–5.

17 Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, et al. Hypoxia-inducible yam tseem ceeb tswj lub peev xwm tumorigenic ntawm glioma qia hlwb. Mob qog noj ntshav. Peb Hlis 2009; 15(6:501–13.

18 Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckhardt KU, et al. Cameron S sawv cev ntawm European cov txheej txheem kev coj ua zoo tshaj plaws ua haujlwm pab pawg: hloov kho European cov txheej txheem kev coj ua zoo tshaj plaws rau kev tswj ntshav qab zib hauv cov neeg mob uas lub raum tsis ua haujlwm. Nephrol Dial Hloov. Peb Hlis 2004; 19(2:47).

19 Kab mob raum: Txhim kho cov txiaj ntsig thoob ntiaj teb. KDIGO cov lus qhia txog kev kho mob ntshav qab zib hauv cov kab mob raum ntev. Raum Int Suppl. 2012 Jul; 2(4): 279–335.

20 National Raum Foundation. Anaemia. New York; 2021. Muaj los ntawm: https://www.kidney.org/professionals/guidelines/guidelines_ commentaries/anemia.

21 MacGinley RJ, Walker RG. Cov txheej txheem kev kho thoob ntiaj teb rau kev mob ntshav qab zib hauv lub raum mob ntev: dab tsi hloov? Med J Aust. 2013 Jul; 199(2:84–5).

22 Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv thiab Kev Kho Mob Hauv Tebchaws. NICE Guideline (NG203) Kab mob raum mob: tswj ntshav qab zib. London; 2021 Sep 1. Muaj los ntawm: https://www.nice. org. uk/guidance/ng203.

23 British Renal Association. Clinical practice guideline anemia ntawm tus kab mob raum mob. Renal Association Cov Lus Qhia Txog Kev Ua Haujlwm: Anemia ntawm Kab Mob Raum Ntev. Bristol; 2021 Sep 1. Muaj los ntawm: https://ukkidney.org/sites/renal.org/files/Updated- 130220-Anaemia-of-Chronic-Kidney-Disease-1-1.pdf.

24 Chait Y, Kalim S, Horowitz J, Hollot CV, Ankers ED, Germain MJ, et al. Qhov kev nkag siab zoo heev ntawm erythropoietin tsis kam Performance index thiab rooj plaub rau kev ntsuas kev ua haujlwm tshiab. Hemodial Int. 2016 Jul; 20(3:392–8.

25 Tsujita M, Kosugi T, Goto N, Futamura K, Nishhira M, Okada M, et al. Cov txiaj ntsig ntawm kev tswj hwm qib siab hemoglobin ntawm lub raum mus sij hawm ntev hauv cov neeg tau txais kev hloov pauv hauv lub raum: kev sim ntsuas randomized. Nephrol Dial Hloov. 2019 Aug; 34(8):1409–16.

26 Bae MN, Kim SH, Kim YO, Jin DC, Song HC, Choi EJ, et al. Lub koom haum ntawm erythropoietin stimulating tus neeg sawv cev teb nrog kev tuag hauv hemodialysis thiab peritoneal dialysis cov neeg mob. PloS Ib. 2015 Nov; 10(11):e0143348.

27 Kanbay M, Perazella MA, Kasapoglu B, Koroglu M, Covic A. Erythropoiesis stimulatory agent-resistant anemia nyob rau hauv cov neeg mob dialysis: tshuaj xyuas qhov ua rau thiab kev tswj xyuas. Ntshav Purif. 2010 Jan; 29(1):1–2.

28 Ingrasciotta Y, Giorgianni F, Marcianò I, Bolcato J, Pirolo R, Chinellato A, et al. Kev sib piv kev ua tau zoo ntawm biosimilar, siv cov khoom siv thiab lwm yam erythropoiesis-stimulating agents (ESAs) tseem them los ntawm patent nyob rau hauv cov kab mob raum ntev thiab cov neeg mob qog noj ntshav: kev tshawb fawb ntawm cov pej xeem Italian. PLoS Ib. 2016 May; 11(5):e0155805.

29 Minutolo R, Conte G, Cianciaruso B, Bellizzi V, Camocardi A, De Paola L, et al. Hyporesponsiveness rau erythropoiesis-stimulating agents thiab lub raum ciaj sia nyob rau hauv cov neeg mob uas tsis yog-dialysis CKD. Nephrol Dial Hloov. Lub Xya Hli 2012; 27(7):2880–6.

30 Okoro T, Carroll C, Chao J, Laurent SS, Shannon J, Clifton C, et al. SP349 Kev Koom Tes ntawm haiv neeg / haiv neeg nrog erythropoietin stimulating tus neeg sawv cev siv thiab tsis kam rau cov neeg mob hemodialysis. Nephrol Dial Hloov. Lub Rau Hli 2019; 34(1):gfz103–SP349.

31 Kuragano T, Kitamura K, Matsumura O, Matsuda A, Hara T, Kiyomoto H, et al. ESA hyporesponsiveness yog txuam nrog cov xwm txheej tsis zoo hauv kev saib xyuas hemodialysis (MHD) cov neeg mob, tab sis tsis muaj hlau cia. PLoS Ib. 2016 Mar; 11(3):e0147328.

32 Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, et al. Erythropoietic teb thiab cov txiaj ntsig ntawm kab mob raum thiab ntshav qab zib hom 2. New Engl J Med. Sep 2010; 363 (12): 1146–55.

33 Panichi V, Rosati A, Bigazzi R, Paoletti S, Mantuano E, Beati S, et al. Anemia thiab tsis kam mus rau erythropoiesis-stimulating agents raws li prognostic yam nyob rau hauv cov neeg mob hemodialysis: tshwm sim los ntawm RISCAVID txoj kev tshawb no. Nephrol Dial Hloov. 2011 Aug; 26(8):2641–8.

34 Corwin HL, Geter A, Fabian TC, May A, Pearl RG, Heard S, et al. Kev ua tau zoo thiab kev nyab xeeb ntawm epoetin alfa hauv cov neeg mob hnyav. New Engl J Med. 2007 Sep; 357(10): 965–76.

35 Cizman B, Smith HT, Camejo RR, Casillas L, Dhillon H, Mu F, et al. Kev kho mob thiab kev lag luam tshwm sim ntawm erythropoiesis-stimulating tus neeg saib xyuas hyporesponsiveness nyob rau hauv lub sij hawm tom qab bundling. Raum Med. 2020 Sep; 2(5):589–99.

36 Guedes M, Robinson BM, Obrador G, Tong A, Pisoni RL, Pecoits-Filho R. Kev tswj ntshav qab zib hauv cov kab mob raum tsis ua haujlwm ntev: cov lus pom zoo tam sim no, kev coj ua hauv ntiaj teb tiag tiag, thiab cov kev xav ntawm tus neeg mob. Lub raum 360. Peb Hlis 2020, 1(1): 855–62.

37 Xav JB. Kev ntsuam xyuas cov xwm txheej hlau: tshaj li cov ntshav ferritin thiab hloov cov dej saturation. Clin J Am Soc Nephrol. 2006 Sep; 1(1):S4–8.

38 NKF Anemia Working Group. Clinical practice guideline for anemia of chronic heart disease: update 2000. Am J Kidney Dis. 2001 Jan; 37(Suppl 1): S182–238.

39 Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015 May; 372(19): 1832–43.

40 Lindenbaum J, Roman MJ. Nutritional anemia hauv cawv. Am J Clin Nutr. Kaum Ib Hlis 1980; 33(12):2727–35.

41 Karaboyas A, Morgenstern H, Fleischer NL, Vanholder RC, Dhalwani NN, Schaeffner E, et al. Inflammation thiab erythropoiesis-stimulating agent teb nyob rau hauv cov neeg mob hemodialysis: ib tug self-matched longitudinal txoj kev tshawb no ntawm anemia tswj nyob rau hauv lub dialysis tshwm sim thiab xyaum xyaum ua qauv (DOPPS). Raum Med. Peb Hlis 2020; 2(3): 286–96.

42 Jofré R, Rodriguez-Benitez P, López-Gómez JM, Pérez-Garcia R. Inflammatory syndrome nyob rau hauv cov neeg mob ntawm hemodialysis. J Am Soc Nephrol. 2006 Dec; 17(12): S274–80.

43 Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome nyob rau hauv cov neeg mob dialysis: ua rau thiab qhov tshwm sim. Am J Raum Dis. 2003 Nov; 42(5):864–81.

44 Schulman G. Kev noj zaub mov tsis zoo thiab o: koob tshuaj lim ntshav hauv cov neeg mob hemodialysis: cuam tshuam rau kev noj haus. Semin Dial. 2004 Nov; 17(6:479–88).

45 Nassar GM, Ayus JC. Cov teeb meem sib kis ntawm hemodialysis nkag. Raum Int. 2001 Jul; 60(1:1–13).

46 Macdougall IC, Cooper AC. Erythropoietin tsis kam: lub luag haujlwm ntawm o thiab proinflammatory cytokines. Nephrol Dial Hloov. 2002 Nov; 17(11:39–43).

47 Xu G, Luo K, Liu H, Huang T, Fang X, Tu W. Kev nce qib ntawm o thiab oxidative kev nyuaj siab nyob rau hauv cov neeg mob raum mob. Ren Fail. 2015 Jan; 37(1:45–9.

48 Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, urinary antimicrobial peptide synthesized nyob rau hauv daim siab. J Biol Chem. Peb Hlis 2001; 276(11): 7806–10.

49 Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin tswj cov cellular hlau efflux los ntawm kev khi rau ferroportin thiab inducing nws internalization. Kev tshawb fawb. 2004 Dec; 306(5704): 2090–3.

50 De Domenico I, Ward DM, Kaplan J. Hepcidin regulation: ironing out the details. J Clin Invest. 2007 Lub Xya Hli; 117(7): 1755–8.

51 Liu XB, Nguyen NB, Marquess KD, Yang F, Haile DJ. Kev tswj hwm ntawm hepcidin thiab ferroportin qhia los ntawm lipopolysaccharide hauv splenic macrophages. Ntshav Cells Mol Dis. 2005 Jul; 35(1:47–56).

52 Ganz T, Nemeth E. Hepcidin thiab hlau homeostasis. Biochim Biophys Acta. Sep 2012; 1823 (9): 1434–43.

53 Locatelli F, Fishbane S, Thaiv GA, Macdougall IC. Targeting hypoxia-inducible yam tseem ceeb rau kev kho mob ntshav qab zib hauv cov neeg mob raum mob ntev. Yog J Nephrol. 2017 Peb Hlis; 45(3):187–99 : kuv.

54 Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay rau human serum hepcidin. Ntshav. 2008 Nov; 112(10): 4292–7.

55 Peslova G, Petrak J, Kuzelova K, Hrdy I, Halada P, Kuchel PW, et al. Hepcidin, cov tshuaj hormones ntawm cov hlau metabolism, raug khi tshwj xeeb rau -2-macroglobulin hauv cov ntshav. Ntshav. 2009 Lub Ib Hlis; 113(24): 6225–36.

56 Wrighting DM, Andrews NC. Interleukin -6 induces hepcidin qhia los ntawm STAT3. Ntshav. 2006 Nov; 108(9):3204–9.

57 BAMBOLA OF. Cov qauv ntawm kev tiv thaiv rau erythropoietin-stimulating cov neeg ua haujlwm hauv cov kab mob raum ntev. Raum Int. 2011 Sep; 80(5): 464–74.

58 Koenig KG, Lindberg JS, Zerwekh JE, Padalino PK, Cushner HM, Copley JB. Dawb thiab tag nrho 1,25-dihydroxy vitamin D qib hauv cov neeg mob raum. Raum Int. 1992 Jan; 41(1): 161–5.

59 Del Vecchio L, Pozzoni P, Andrulli S, Locatelli F. Inflammation and resistance to treatment with recombinant human erythropoietin. J Ren Nutr. 2005 Jan; 15(1): 137–41.

60 Coe LM, Madathil SV, Casu C, Lanske B, Rivella S, Sitara D. FGF-23 yog tus tswj tsis zoo ntawm kev ua ntej yug menyuam thiab postnatal erythropoiesis. J Biol Chem. 2014 Plaub Hlis Ntuj; 289(14): 9795–810.

61 Usui T, Zhao J, Fuller DS, Hanafusa N, Hasegawa T, Fujino H, et al. Lub koom haum ntawm erythropoietin Resistance thiab fibroblast kev loj hlob yam

23 nyob rau hauv cov neeg mob dialysis: tshwm sim los ntawm Japanese dialysis tshwm sim thiab xyaum xyaum xyaum. Nephrology. 2021 Jan; 26(1:46–53). 62 Maruyama N, Otsuki T, Yoshida Y, Nagura C, Kitai M, Shibahara N, et al. Ferric citrate txo qhov kev loj hlob ntawm fibroblast 23 thiab txhim kho erythropoietin teb rau cov neeg mob hemodialysis. Yog J Nephrol. Lub Xya Hli 2018; 47(6):406–14 : kuv.

63 Bamonti-Catena F, Buccianti G, Porcella A, Valenti G, Como G, Finazzi S, et al. Kev ntsuas folate hauv cov neeg mob ntawm kev kho hemodialysis tsis tu ncua. Am J Raum Dis. Peb Hlis 1999; 33(3):492–7 : kuv.

64 Bridges KR, Hoffman KE. Cov teebmeem ntawm ascorbic acid ntawm cov metabolism hauv intracellular ntawm hlau thiab ferritin. J Biol Chem. Peb Hlis 1986; 261(30):14273-7.

65 Ikee R, Tsunoda M, Sasaki N, Sato N, Hashimoto N. Cov kev kho mob cuam tshuam nrog cov qib tooj liab thiab cov txiaj ntsig zoo ntawm sevelamer hauv cov neeg mob hemodialysis. Urol Nephrol Cov. Peb Hlis 2013; 45(3): 839–45.

66 Tan BL, Norhaizan ME, Liew WP. Khoom noj khoom haus thiab oxidative kev nyuaj siab: phooj ywg los yog foe? Oxid Med Cell Longev. 2018 Lub ib hlis ntuj 2018: 9719584.

67 Calò LA, Davis PA, Pagnin E, Bertipaglia L, Naso A, Piccoli A, et al. Carnitine-mediated txhim kho cov lus teb rau erythropoietin suav nrog induction ntawm haem oxygenase-1: kev tshawb fawb hauv tib neeg thiab tus qauv tsiaj. Nephrol Dial Hloov. Peb Hlis 2008; 23(3:890–5.

68 Killen JP, Brenninger VL. Hydroxocobalamin supplementation thiab erythropoiesis-stimulating tus neeg saib xyuas hyporesponsiveness hauv cov neeg mob hemodialysis. Nephrology. 2014 Mar; 19(3): 164–71.

69 Obi Y, Mikami S, Hamano T, Obi Y, Tanaka H, ​​Shimomura A, et al. Intravenous Vitamin B6 tsub kom tsis kam mus rau erythropoiesis-stimulating agents nyob rau hauv cov neeg mob hemodialysis: ib tug randomized tswj mus sib hais. J Ren Nutr. 2016 Nov; 26(6):380–90.

70 Azizi M, Rousseau A, Ezan E, Guyene TT, Michelet S, Grognet JM, et al. Mob angiotensin-hloov enzyme inhibition nce qib plasma ntawm lub ntuj qia cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest. 1996 Feb; 97(3): 839–44.

71 Latcha S. Kev tswj ntshav qab zib hauv cov neeg mob qog noj ntshav uas muaj kab mob raum ntev. Semin Dial. 2019 Nov; 32(6:513–9.

72 Drüeke T. Hyporesponsiveness rau recombinant human erythropoietin. Nephrol Dial Hloov. 2001 Peb.; 16(7:25–8.

73 Del Vecchio L, Locatelli F. Ib qho kev piav qhia ntawm cov teeb meem kev nyab xeeb ntsig txog erythropoiesis-stimulating agents rau kev kho mob ntshav qab zib hauv cov neeg mob uas mob raum. Expert Opin Drug Safe. 2016 Aug; 15(8):1021–30.

74 Casadevall N. Cellular mechanism ntawm kev tiv thaiv erythropoietin. Nephrol Dial Hloov. 1995 Jan; 10(Suppl 6:27–30).

75 Fuller DS, Pisoni RL, Bieber BA, Port FK, Robinson BM. Lub DOPPS xyaum saib xyuas rau US dialysis care: hloov tshiab ntawm kev hloov hauv kev tswj ntshav qab zib 2 xyoo rau hauv pob. Am J Raum Dis. 2013 Dec; 62(6): 1213–6.

76 Del Vecchio L, Longhi S, Locatelli F. Kev nyab xeeb kev txhawj xeeb txog kev kho mob hlau hauv cov neeg mob uas mob raum. Clin Kidney J. 2016 Plaub Hlis Ntuj 9(2):260–7.

77 Macdougall IC, White C, Anker SD, Bhandari S, Farrington K, Kalra PA, et al. Intravenous hlau nyob rau hauv cov neeg mob tau kho hemodialysis. N Engl J Med. 2019 Lub Ib Hlis; 380(5): 447–58.

78 Agarwal R, Kusek JW, Pappas MK. Ib qho kev sim randomized ntawm cov hlab ntsha thiab qhov ncauj hlau hauv cov kab mob raum ntev. Raum Int. Peb Hlis 2015; 88(4):905–14 : kuv.

79 Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, et al. FINDCKD: ib qho randomized sim ntawm intravenous ferric carboxymaltose piv rau qhov ncauj hlau nyob rau hauv cov neeg mob uas mob raum kab mob thiab hlau deficiency anemia. Nephrol Dial Hloov. 2014 Nov; 29(11): 2075–84.

80 Rosenberger C, Mandriota S, Jürgensen JS, Wiesener MS, Hörstrup JH, Frei U, et al. Kev nthuav qhia ntawm hypoxia-inducible factor-1 thiab - 2 hauv hypoxic thiab ischemic nas raum. J Am Soc Nephrol. 2002 Jul; 13(7): 1721–32.

81 Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, et al. Lub hom phiaj ntawm HIF- mus rau von Hippel-Lindau ubiquitylation complex los ntawm O2- tswj hwm prolyl hydroxylation. Kev tshawb fawb. 2001 Plaub Hlis Ntuj; 292(5516): 468–72.

82 Kular D, Macdougall IC. HIF stabilizers nyob rau hauv kev tswj ntawm lub raum anemia: los ntawm lub rooj ntev zaum mus rau lub txaj rau menyuam yaus. Pediatr Nephrol. Peb Hlis 2019; 34(3): 365–78.

83 Panwar B, Gutiérrez OM. Kev puas tsuaj ntawm hlau metabolism thiab anemia hauv cov kab mob raum ntev. Semin Nephrol. 2016 Jul;36(4):252–61.

84 Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, Onoue T, et al. Kev ua tau zoo thiab kev nyab xeeb ntawm daprodustat piv nrog darbepoetin alfa hauv Japanese hemodialysis cov neeg mob uas muaj ntshav qab zib: ib qho randomized, ob-dig muag, theem 3 mus sib hais. Clin J Am Soc Nephrol. 2020 Aug; 15(8): 1155–65.

85 Eckardt KU, Agarwal R, Farag YM, Jardine AG, Khawaja Z, Koury MJ, et al. Ntiaj teb no Phase 3 qhov kev pab cuam ntawm vadadustat rau kev kho mob ntshav qab zib ntawm cov kab mob hauv lub raum ntev: qhov laj thawj, kev tsim qauv, thiab cov yam ntxwv ntawm cov neeg mob ntshav lim ntshav hauv INNO- 2VATE kev sim. Nephrol Dial Hloov. 2020.

86 Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, et al. Roxadustat rau anemia hauv cov neeg mob lub raum tsis tau txais kev lim ntshav. New Engl J Med. 2019 Sep; 381(11):1001–10.

87 Macdougall IC, Akizawa T, Berns JS, Bernhardt T, Krueger T. Cov teebmeem ntawm solid-state hauv kev kho mob ntshav qab zib hauv CKD. Clin J Am Soc Nephrol. 2019 Jan; 14(1):28–39. 88 Yap DY, McMahon LP, Hao CM, Hu N, Okada H, Suzuki Y, et al. Cov lus pom zoo los ntawm Asian pacific Society of Nephrology (APSN) txog kev siv HIF-PH inhibitors tsim nyog. Nephrology. 2021 Peb; 26(2):105–18.

89 Yousaf F, Spinowitz B. Hypoxia-inducible factor stabilizers: ib txoj hauv kev tshiab los txo BP thaum pab hemoglobin? Curr Hypertens Rep. 2016 Mar;18(3):23.

90 Seeley TW, Sternlicht MD, Klaus SJ, Neff TB, Liu DY. Induction ntawm erythropoiesis los ntawm hypoxia-inducible yam prolyl hydroxylase inhibitors yam tsis muaj kev txhawb nqa ntawm qog pib, kev loj hlob, lossis metastasis hauv VEGFsensitive qauv ntawm spontaneous cancer mis. Hypoxia. Peb Hlis 2017; 5:1–9.

91 Nkauj SN, Tomosugi N, Kawabata H, Ishikawa T, Nishikawa T, Yoshizaki K. Down-txoj cai ntawm hepcidin tshwm sim los ntawm kev kho mob mus sij hawm ntev nrog cov tshuaj tiv thaiv-IL-6 receptor antibody (tocilizumab) txhim kho anemia ntawm o hauv multicentric Castleman kab mob. Ntshav. 2010 Nov; 116(18):3627–34.

92 Casper C, Chaturvedi S, Munshi N, Wong R, Qi M, Schaffer M, et al. Kev soj ntsuam ntawm inflammatory thiab anemia-txog biomarkers nyob rau hauv ib tug randomized, ob-dig muag, placebo-tswj txoj kev tshawb no ntawm siltuximab (anti-IL6 monoclonal antibody) nyob rau hauv cov neeg mob uas muaj kab mob multicentric Castleman. Clin Cancer Res. 2015 Peb.; 21(19):4294–304.

93 Masajtis-Zagajewska A, Nowicki M. Cov nyhuv ntawm atorvastatin ntawm kev tswj cov metabolism hauv hlau hauv cov neeg mob uas muaj kab mob raum ntev: kev kawm randomized ob-dig muag crossover. Ren Fail. Peb Hlis 2018, 40(1): 700-9.

94 Johnson DW, Pascoe EM, Badve SV, Dalziel K, Cass A, Clarke P, et al. Ib qho randomized, placebo-tswj kev sim ntawm pentoxifylline ntawm erythropoiesis-stimulating tus neeg saib xyuas hyporesponsiveness hauv cov neeg mob ntshav qab zib nrog CKD: kev tuav erythropoietin tsis kam nrog oxpentifylline (HERO) sim. Am J Raum Dis. 2015 Jan; 65(1:49–57).

95 Yin K, Agrawal DK. Vitamin D thiab inflammatory kab mob. J Inflamm Res. Peb Hlis 2014; 7:69–87.

96 Moorthi RN, Kandula P, Moe SM. Qhov zoo tshaj plaws vitamin D, calcitriol, thiab vitamin D analog hloov nyob rau hauv cov kab mob raum ntev: mus rau D los yog tsis mus rau D: uas yog cov lus nug. Curr Opin Nephrol Hypertens Cov. 2011 Jul; 20(4:354–9.

97 Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, et al. Tiv thaiv cov hlau tswj hepcidin los ntawm vitamin D. J Am Soc Nephrol. 2014 Mar; 25(3:564–72.

98 Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al. Cov ntsiab lus tseem ceeb ntawm 2017 KDIGO mob raum kab mob - ntxhia thiab pob txha mob (CKD-MBD) cov lus qhia hloov tshiab: dab tsi hloov thiab vim li cas nws tseem ceeb. Raum Int. 2017 Jul;92(1:26–36).

99 Trunzo JA, McHenry CR, Schulak JA, Wilhelm SM. Kev cuam tshuam ntawm parathyroidectomy ntawm anemia thiab koob tshuaj erythropoietin hauv cov neeg mob lub raum kawg ntawm cov neeg mob hyperparathyroidism. Kev phais. 2008 Dec; 144(6:915–9.

100 Tanaka M, Yoshida K, Fukuma S, Ito K, Matsushita K, Fukagawa M, et al. Cov txiaj ntsig ntawm kev kho mob hyperparathyroidism theem nrab ntawm kev txhim kho hauv cov ntshav ntshav: tau los ntawm MBD-5D txoj kev tshawb fawb. PLoS Ib. 2016 Nov; 11(10): e0164865.

101 Kuwahara M, Mandai S, Kasagi Y, Kusaka K, Tanaka T, Shikuma S, et al. Teb rau erythropoiesis-stimulating agents thiab lub raum ciaj sia nyob rau hauv cov neeg mob uas mob raum kab mob. Clin Exp Nephrol. 2015 Aug; 19(4): 598–605.

Henry HL Wu a, b Rajkumar Chinnadurai b, c

Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob Raum, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK;

b Kws qhia ntawv ntawm Biology, Tshuaj, thiab Kev Noj Qab Haus Huv, University of Manchester, Manchester, UK;

c Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford, UK