Novel Approach To Unpleasant Symptom Clusters Surrounding Pruritus in Patients With Chronic Kidney Disease and On Dialysis Therapy
May 26, 2022
Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com
Lub hom phiaj ntawm kev tshuaj xyuas
Cov kab mob raum ntev-associated-pruritus (CKDaP] yog ib qho tsos mob tshwm sim hauv cov neeg mob uas muaj kab mob raum kawg [ESKD)] tab tom lim ntshav. CKD-aP feem ntau tshwm sim nrog rau lwm cov tsos mob tsis zoo thiab tej zaum yuav muaj cov kab mob hu ua pawg uas muaj kev sib koom ua ke uas cuam tshuam rau tus neeg mob txog kev noj qab haus huv ntawm lub neej zoo (HRQol]. Kev tshuaj xyuas qhov cuam tshuam ntawm CKDaP thiab nws txoj kev koom tes nrog lwm cov tsos mob qhia los ntawm cov neeg mob lim ntshav, cov txiaj ntsig kho mob ntawm kev kho mob pruritus thiab nws cov kev cuam tshuam rau lwm cov tsos mob kuj tau hais txog. Kev lim ntshav thiab cuam tshuam nrog cov txiaj ntsig tsis zoo, suav nrog kev pheej hmoo ntawm kev kis kab mob, thiab mus pw hauv tsev kho mob thiab kev tuag. Txawm hais tias cov teebmeem tsis zoo no, CKDaP tseem tsis tau lees paub thiab tsis muaj kev kho mob hauv kev kho mob, CKD-aP feem ntau cuam tshuam nrog lwm cov tsos mob. pw tsaug zog zoo, ntxhov siab vim, kev nyuaj siab, thiab mob.Clinical kev tshawb fawb ntawm antip ruritic kev kho mob qhia tau hais tias txo qhov khaus khaus kuj yuav txo tau lwm yam tsos mob, xws li pw tsaug zog tsis zoo.
Cov ntsiab lus: CKD-aP thiab nws cov tsos mob cuam tshuam yog tswj tsis tau zoo hauv kev kho mob. Kev nkag siab ntau dua thiab kev paub txog CKD-aP thiab nws cov tsos mob ib puag ncig hauv cov neeg mob ntshav lim ntshav tuaj yeem txhim kho lawv cov kev tswj xyuas tag nrho cov tsos mob thiab HRQol.
Keywords: mob raum mob, dialysis, pruritus, symptom pawg, tsis kaj siab tsos mob
Nyem qhov no kom paub txog cov txiaj ntsig ntawm cistanche tshuaj ntsuab
Taw qhia
Cov neeg uas muaj kab mob hauv lub raum kawg (ESKD), tseem hu ua theem 5mob raum mob (CKD), muaj lub nra hnyav ntawm cov tsos mob, uas ua rau tsis zoo rau lawv lub cev thiab lub siab lub ntsws ntsig txog lub neej zoo (HRQoL) nrog rau lawv lub peev xwm ua haujlwm txhua hnub [1,2]. Cov neeg uas muaj ESKD uas xav tau hemodialysis rau lub raum hloov kev kho mob muaj txiaj ntsig txo qis ntawm lawv cov tsos mob ua rau muaj sia nyob ntev [3,4], qhia txog qhov cuam tshuam loj heev rau cov tsos mob no rau lawv lub neej. Yog li ntawd, kev txheeb xyuas qhov tseeb thiab txo qis ntawm cov tsos mob yog qhov tseem ceeb rau kev tswj hwm ntawm cov tib neeg no. CKD-associated pruritus (CKD-aP; yav tas los hu ua uremic pruritus) yog ib qho mob hnyav thiab hnyav tshaj qhia los ntawm cov neeg mob CKD, thiab feem ntau "Lub Tsev Haujlwm Saib Xyuas Tshuaj, Division of Nephrology Hypertension thiab Raum Hloov, University of California Irvine (UCL), Txiv kab ntxwv, 5Division of Nephrology, Hypertension thiab raum Transplantation, University of California, Irvine, California, USA, cDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK; Tsev Kho Mob University of Leicester NHS Trust, Leicester, UK thiab "Department of Biobehavioral Nursing Science, University of Illinois ntawm Chicago, College of Nursing, Chicago, Illinois, USA
Kev xa mus rau Mark B.Lockwood, Ph.D., MSN, RN, Pronouns: he/him/his, Assistant Professor, Department of Biobehavioral Nursing Science, University of Ilinois at Chicago, College of Nursing. 845 South Damen Avenue, Room 658(MC802), Chicago, IL 60612-7350, USA. Tel: plus 312413 5181; fax: plus 312 996 4979;e-mail:lockmar@uic.edu Curr Opin Nephrol Hypertens 2022, 31:63-71 DOI:10.1097/MNH.0000000000000752
Qhov no yog ib tsab xov xwm qhib tau muab faib raws li cov ntsiab lus ntawm Creative Commons Attribution-Non-Commercial-No Derivatives License 4. nws yog raug nplua. Kev ua haujlwm tsis tuaj yeem hloov pauv txhua txoj hauv kev lossis siv kev lag luam yam tsis tau tso cai los ntawm phau ntawv xov xwm.
TSEEM CEEB
● Cov kab mob hauv lub raum-txuas ntxiv pruritus (CKD-aP) yog ib qho tshwm sim, tsis paub txog cov tsos mob hauv cov neeg mob uas muaj kab mob raum kawg (ESKD) tab tom lim ntshav.
● Cov kev tshawb fawb tau pom tias CKD-aP cuam tshuam HRQol hauv cov neeg mob ESKD tab tom lim ntshav thiab cuam tshuam nrog cov txiaj ntsig tsis zoo, suav nrog kev pheej hmoo kis mob, mus pw hauv tsev kho mob, thiab kev tuag.
● Cov etiology ntawm CKD-aP tsis to taub tag nrho, tab sis ob peb lub tswv yim muaj peev xwm cuam tshuam rau lub cim ntawm pruritus, suav nrog (1) tso tawm ntawm uremic toxins hauv daim tawv nqaij thiab cov ntaub so ntswg subcutaneous; (2)tiv thaiv kab mobqhov systemdysregulation thiabmob; (3) peripheral neuropathy; (4) dysregulation ntawm endogenous opioid system; thiab (5) kev hloov pauv hauv cov qauv thiab kev ua haujlwm ntawm daim tawv nqaij microbiome.
● Muaj pov thawj tias cov tsos mob tshwm sim los ntawm cov neeg mob ESKD tuaj yeem tshwm sim hauv pawg, yog li kev txheeb xyuas cov tsos mob hauv ESKD tuaj yeem pab qhia cov tswv yim tswj cov tsos mob ntawm tus kheej, ua rau kev txhim kho hauv HRQol thiab lwm cov txiaj ntsig kho mob.
· Difelikefalin, peripheral, xaiv KOR agonist, tsis ntev los no tau los ua thawj txoj kev kho mob pom zoo los ntawm US FDA rau kev kho mob ntawm CKD-aP. zuj zus ntxiv thaum CKD nce mus rau ESKD xav tau kev kho lub raum hloov.
Cov tsos mob ntawm cov neeg uas muaj ESKD ntawm hemodialysis yog siab thiab cov tsos mob feem ntau nyuaj. CKD-aP tsis tshua muaj tshwm sim hauv kev sib cais thiab feem ntau ua rau muaj kev ntxhov siab rau cov neeg mob uas tau lim ntshav. Feem ntau, CKD-aP tshwm sim hauv lub hnub qub nrog lwm cov tsos mob tsis zoo uas muaj kev sib koom ua ke ntawm ib leeg thiab ua kom cov neeg mob muaj kev txom nyem. Thaum ob lossis ntau qhov tsos mob tshwm sim thiab muaj feem cuam tshuam, lawv raug hu ua cov tsos mob pawg [7,8]. Vim tias cov tsos mob ntawm tus kheej muaj feem cuam tshuam, lawv tuaj yeem qhia txog cov txheej txheem lom neeg uas tuaj yeem raug tsom rau kev cuam tshuam. Yog li, tsom ib qho tsos mob hauv pawg rau kev cuam tshuam tuaj yeem cuam tshuam rau lwm cov tsos mob hauv ib pawg kab mob. Txawm li cas los xij, cov tsos mob ntawm kev tshawb fawb thoob plaws lub spectrum ntawm CKD yog nyob rau hauv nws cov me nyuam mos thiab xav tau kev tshawb fawb ntxiv los daws cov kev sib raug zoo ntawm cov tsos mob thiab cov txiaj ntsig ntawm tus neeg mob. Kev txheeb xyuas cov tsos mob ntawm cov neeg mob ESKD tab tom lim ntshav tuaj yeem pab qhia txog cov tsos mob, kev pheej hmoo-stratification, thiab kev txhim kho ntawm cov neeg mob kev cuam tshuam los txo cov tsos mob, yog li txo qhov tsis zoo ntawm tus neeg mob HRQoL.
Ntawm no, peb tshuaj xyuas qhov cuam tshuam ntawm kev kho mob ntawm CKD-aP ntawm cov tsos mob tshwm sim thiab cov txiaj ntsig tseem ceeb ntawm tus neeg mob, suav nrog HRQoL, kev pheej hmoo rau kev kis kab mob, mus pw hauv tsev kho mob, thiab kev tuag, hauv cov neeg mob ESKD tab tom lim ntshav. Cov txiaj ntsig kev kho mob muaj peev xwm ntawm kev txo qis CKD-aP thiab cov txiaj ntsig muaj feem cuam tshuam rau lwm cov tsos mob kuj tseem yuav tham txog.
CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS: EPIDEMIOLOGY, PATHOPHYSIOLOGY, THIAB CLINICAL PRESENTATION
Txawm hais tias qhov kev kwv yees ntau tshaj ntawm CKD-aP hauv cov neeg mob lim ntshav sib txawv ntawm kev tshawb fawb txog kev kis mob, cov neeg mob tau tshaj tawm cov ntaub ntawv los ntawm Dialysis Outcomes thiab Practice Patterns Study (DOPPS) qhia tias kwv yees li ob feem peb ntawm cov neeg mob hemodialysis muaj CKD-aP, 37 feem pua ntawm cov kev paub dhau los. Txawm hais tias nws muaj ntau heev, CKD-aP raug saib xyuas los ntawm cov kws kho mob thiab tsis tau tshaj tawm los ntawm cov neeg mob hauv kev kho mob; 17 feem pua ntawm cov neeg mob ib txwm lossis ze li ib txwm mob khaus khaus tsis qhia lawv cov tsos mob. rau leej twg [5,11].
Lub complex pathophysiology ntawm mob khaus khaus tseem tsis tau nkag siab; Txawm li cas los xij, nws yuav yog qhov tshwm sim ntawm kev tso tawm ntawm pruritogens (piv txwv li, histamine, prostaglandins, cytokines, neuropeptides, thiab proteases) los ntawm keratinocytes, lub cev tiv thaiv kab mob, lossis cov neurons nyob ze ntawm daim tawv nqaij [12. Cov kab mob pruritus ntev tuaj yeem txhais tau tias yog qhov tsis xis nyob ntawm daim tawv nqaij ua rau muaj lub siab xav kos, uas nyob ntev dua 6 hli [13]. CKD-aP yog ib qho mob uas tshwm sim los ntawm pruritus ntsig txog CKD, uas tsis tau piav qhia los ntawm lwm yam etiology [12". Kev txheeb xyuas thiab kev kuaj mob ntawm CKD-aP yog qhov nyuaj los ntawm nws qhov kev nthuav qhia kho mob sib txawv. Nrog CKD-aP hais txog qhov hnyav thiab qhov chaw faib tawm ntawm pruritus thaum lub sij hawm, Pruritus siv tuaj yeem nyob ntawm qhov tsis xis nyob me me mus rau qhov tsis txaus ntseeg thiab cuam tshuam [14]. los yog tuaj yeem ua rau thaj chaw tshwj xeeb ntawm lub cev, feem ntau yog lub ntsej muag, nraub qaum, lossis fistula caj npab [15]. Pruritus tuaj yeem tshwm sim txhua lub sijhawm thiab nws qhov tshwm sim lossis kev siv tsis cuam tshuam rau lub sijhawm ntawm kev lim ntshav [5,16,17 Ntau tus neeg mob yws yws ntawm cov tsos mob hnyav thaum hmo ntuj thaum lawv tuaj yeem pom ntau dua [5,18]. Cov kev tshawb fawb soj ntsuam ntsuas lub sijhawm ntawm CKD-aP qhia tau tias pruritus feem ntau tshwm sim rau ntau xyoo|19,20]. ntstst rau lwm yam khaus ntawm cov kab mob dermatological, CKD-aP tsis cuam tshuam nrog thawj cov tsos mob ntawm daim tawv nqaij, txawm hais tias qee cov neeg mob tuaj yeem tshwm sim nrog cov kab mob hauv nruab nrab [14]. Txawm li cas los xij, thaum cov tawv nqaij qhuav (xerosis) tsis xav tias yog thawj qhov ua rau tus mob, nws nquag tshwm sim nrog CKD-aP thiab tuaj yeem ua rau khaus khaus hnyav [21].
Lub etiology ntawm CKD-aP tsis to taub tag nrho, tab sis ob peb lub tswv yim tau raug cuam tshuam rau hauv tiam neeg ntawm pruritus, suav nrog (1) tso tawm ntawm uremic toxins hauv daim tawv nqaij thiab cov ntaub so ntswg subcutaneous; (2) kev tiv thaiv kab mob thiab o; (3) ) peripheral neuropathy; (4) dysregulation ntawm endogenous opioid system thiab; (5) kev hloov pauv hauv cov qauv thiab kev ua haujlwm ntawm daim tawv nqaij microbiome.
BURDEN OF CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS IN HEMODIALYSIS PATIENTS
Kev cuam tshuam ntawm cov kab mob raum ntev-koom nrog pruritus ntawm cov txiaj ntsig kho mob
CKD-aP yog qhov tsis txaus siab thiab muaj feem cuam tshuam rau cov neeg mob uas muaj hemodialysis, thiab tau cuam tshuam nrog cov txiaj ntsig kho mob hnyav dua, suav nrog kev pheej hmoo ntau dua ntawm kev kis kab mob, mus pw hauv tsev kho mob, thiab kev tuag [6", 23]. pruritus feem ntau yuav thim tawm ntawm kev lim ntshav, tsis tau teem caij lim ntshav, thiab siv sijhawm ntev dua kom rov zoo los ntawm kev lim ntshav, piv nrog cov neeg mob uas tsis mob pruritus [6"]. Ib yam li ntawd, ib qho kev tshawb fawb loj rov qab los ntawm US cov neeg mob hemodialysis (n=38,315) kuj tau pom ntau dua ntawm cov kev tsis txaus siab hemodialysis, nrog rau kev siv tshuaj ntau ntxiv (cov tshuaj tua kab mob hauv cov hlab ntsha [IV], erythropoietin-stimulating agents, thiab IV hlau) ntawm cov neeg mob uas nws tus kheej tau tshaj tawm qhov mob hnyav heev thaum piv rau cov neeg uas tsis raug mob los ntawm pruritus [24].
Kev cuam tshuam rau kev noj qab haus huv thiab lub neej zoo
Many observational studies have shown CKD-aP is associated with reduced HRQoL for patients with ESKD undergoing hemodialysis [6",19,20,23,25-33]. Figure 1 provides an overview of patient-reported outcome instruments used to capture CKD-aP HRQoL, with validated measures described in Table 1. Among the largest epidemiological studies was a recent analysis of the international DOPPS patient cohort (Phases 4-6; 2009-2018)that included >23, 000 cov neeg mob hemodialysis los ntawm 21 lub teb chaws, uas ntsuas kev sib raug zoo ntawm pruritus mob hnyav thiab cov neeg mob tau tshaj tawm cov txiaj ntsig [6]. Qhov khaus khaus tau raug soj ntsuam los ntawm kev siv cov lus nug khaus los ntawm tus kheej-qhia rau raum Kab Mob Zoo ntawm Lub Neej 36-cov ntawv tshawb fawb luv luv (KDQOL-36), uas nug cov neeg mob txog qhov uas lawv tau thab los ntawm khaus ntawm daim tawv nqaij. nyob rau hauv 4 lub lis piam dhau los (5- pawg scale:'tsis tag rau 'hnyav heev'). QoL ntsig txog kev noj qab haus huv tau raug soj ntsuam los ntawm kev siv 12-Kev Tshawb Fawb Kev Noj Qab Haus Huv Short-Form (SF-12), ib feem ntawm KDQOL-36 uas muab kev ntsuas dav dav ntawm HRQoL ntawm lub hlwb thiab lub cev los ntawm ib qho MCS (MCS) thiab lub cev qhov ntsuas (PCS) cov qhab nia (ntau:0-100).
Cov neeg mob hemodialysis uas tau tshaj tawm tias muaj kev cuam tshuam loj heev los ntawm pruritus muaj MCS thiab PCS cov qhab nia 6.7 thiab 9.1 qis dua cov neeg mob uas tsis muaj kev cuam tshuam los ntawm pruritus (cov kws sau ntawv sau tseg ib qho 3- rau 5-qhov sib txawv tau suav tias yog kev kho mob)[ 6"]. Tsis tas li ntawd, cov ntaub ntawv ntev los ntawm Ger-man Epidemiological Hemodialysis Itch Study (GEHIS) uas tau ua raws li cov neeg mob hemodialysis nrog CKD-aP (N=212) nyob rau hauv ib lub sijhawm 4- xyoo qhia tias HRQoL(suav los ntawm SF-12 daim ntawv nug) tau txhim kho ntawm cov neeg mob uas tsis tau tshaj tawm CKD-aP tom qab 4 xyoos [29].
Kev sib koom ua ke ntawm cov kab mob hauv lub raum-koom nrog pruritus thiab lwm yam tsos mob
Cov tsos mob muaj peev xwm suav nrog cov kab mob hauv lub raum-kwv yees nrog pruritus Muaj pov thawj tias cov tsos mob tshwm sim los ntawm cov neeg mob ESKD tuaj yeem tshwm sim hauv pawg. Cov kab mob-tom pawg tuaj yeem txhais tau tias yog ob lossis ntau cov tsos mob tshwm sim uas muaj feem cuam tshuam rau ib leeg, tuaj yeem sib koom ua ke, thiab tshwm sim ntawm nws tus kheej ntawm lwm cov tsos mob [7]. Lub tswv yim tseem ceeb ntawm cov tsos mob ntawm kev tshawb fawb yog qhov kev xav tias alleviating ib tus tsos mob tuaj yeem txo qhov hnyav ntawm lwm cov tsos mob suav nrog hauv pawg [8]. Kev txheeb xyuas cov tsos mob hauv ESKD tuaj yeem pab qhia cov tswv yim tswj cov tsos mob ntawm tus kheej, ua rau kev txhim kho hauv HRQoL thiab lwm cov txiaj ntsig kho mob.
Txawm hais tias daim ntawv thov ntawm cov tsos mob ntawm kev tshawb fawb rau CKD tseem yog ib qho kev tshwm sim, tsis zoo li oncology qhov twg nws tau tsim zoo, ntau cov kev tshawb fawb luam tawm tau sim txheeb xyuas cov tsos mob hauv cov neeg mob ESKD tab tom lim ntshav [34,35",36-42, 43"] ib. Qhov sib xyaw ntawm cov tsos mob tau txheeb xyuas los ntawm cov kev tshawb fawb no tau sib txawv nyob ntawm cov cuab yeej ntsuas tshwj xeeb thiab cov txheej txheem txheeb cais siv [38]. Hais txog cov tsos mob ntawm pawg, ib qho tseem ceeb yog tias muaj ntau cov tsos mob tshwm sim hauv CKD / ESKD tsis tau raug txiav txim siab hauv txoj kev no yav dhau los hauv nephrology. Yog li, muaj lub sijhawm zoo los xav txog CKD / ESKD cov tsos mob sib txawv, siv cov qauv latent los txiav txim siab txog kev sib raug zoo ntawm cov tsos mob, nrog rau lub tswv yim uas cuam tshuam rau cov tsos mob nrog kev sib koom ua ke lom neeg thiab muaj kev cuam tshuam rau ntau yam tsos mob hauv cov tsos mob (xws li. pruritis / pw tsaug zog /qaug zog/ mob). Txog tam sim no, kev ua haujlwm me me tau ua tiav los tsim kom muaj cov tsos mob ntawm pawg hauv nephrology, txawm hais tias muaj pov thawj tias CKD-aP tau pom muaj tshwm sim nrog lwm cov tsos mob tshwm sim hauv cov neeg mob ESKD, suav nrog kev pw tsaug zog, kev nyuaj siab, mob, thiab nyob tsis tswm. ob txhais ceg syndrome, qhia tau hais tias tej zaum yuav muaj ib tug tshwj xeeb cov tsos mob (Fig. 2).
Pw tsaug zog thiab qaug zog
Many studies have reported a negative association between CKD-aP as well as sleep quality and quantity among patients with ESKD undergoing hemo-dialysis[6",19,20,23,28,33,44].In the recent DOPPS analysis (Phases 4-6), poor sleep quality(defined as ≥3 nights in the past week of restless sleep as assessed by the sleep question from the Center for Epidemiologic Studies-Depression [CES-D] sleep questionnaire) was more commonly reported by patients bothered (vs not bothered) by pruritus. Furthermore, the prevalence of patients who reported feeling 'washed out or drained' was >2-fold ntau dua rau cov neeg uas muaj mob me me mus rau qhov khaus heev dua li cov uas tsis muaj kev cuam tshuam los ntawm pruritus[60]. Ib qho kev soj ntsuam ua ntej ntawm DOPPS pawg (Phases 1 thiab 2;1996-2004) pom tias ~ 45 feem pua ntawm cov neeg mob uas muaj mob me me mus rau qhov mob hnyav tau qhia txog kev pw tsaug zog tsis zoo hauv kev sib piv nrog 29 feem pua ntawm cov neeg mob uas tsis muaj lossis mob me me [23 ].Hauv qhov kev tshuaj ntsuam no, kev pw tsaug zog tsis zoo tau raug ntaus nqi ntau dua ntawm kev tuag (17 feem pua) hauv cov neeg mob pruritus vs cov tsis muaj pruritus [23].
Qhov kev xav ntev ntev ITCH National Registry Study soj ntsuam cov keeb kwm ntawm CKD-aP nyob rau hauv ib pawg ntawm US hemodialysis cov neeg mob (N=103) tau soj ntsuam ib qho kev koom tes tseem ceeb ntawm pruritus siv thiab pw tsaug zog cuam tshuam los ntawm khaus raws li kev soj ntsuam los ntawm ob qho kev ntsuas pw tsaug zog (ib qho hloov kho ntawm Itch Medical Outcomes Study [MOS] daim ntawv nug pw tsaug zog thiab cov lus nug pw tsaug zog los ntawm BriefItching Inventory [BII questionnaire) [19].
Txoj kev tshawb fawb GEHIS tau txheeb xyuas cov ntaub ntawv pw tsaug zog rau 860 HD cov neeg mob uas muaj thiab tsis muaj CKD-aP. Nws tau pom tias feem ntau ntawm cov neeg mob uas muaj CKD-aP (54.5 feem pua) qhia tias nyuaj pw tsaug zog ntau dua ib zaug hauv ib lub lis piam, thaum 48.3 feem pua yws yws ntawm kev pw tsaug zog tsis zoo [20]. Cov kws sau ntawv tau tshaj tawm tias kev puas tsuaj ntawm kev pw tsaug zog tsis zoo yog cuam tshuam nrog kev muaj pruritus, tab sis tsis yog nrog qhov mob hnyav [20].
Kev nyuaj siab thiab kev ntxhov siab
Ntau qhov kev tshawb fawb kuj tau pom muaj kev sib raug zoo ntawm CKD-aP thiab kev nyuaj siab [6,28,31,45]. Kev soj ntsuam ntawm DOPPS tau pom tias cov neeg mob hemodialysis uas raug mob los ntawm pruritus feem ntau yuav muaj cov tsos mob ntawm kev nyuaj siab (raws li kev soj ntsuam los ntawm tus kws kho mob kev nyuaj siab [Phases 1 thiab 2] 【23】 thiab qhia tus kheej CES-D qhab nia 之1{{23 }} 【Phases 4-6])[6"]. Kev tshawb nrhiav ntu ntu ntawm cov neeg mob hemodialysis hauv Brazil (N=980) kuj tau pom tias cov neeg mob uas nws tus kheej tau tshaj tawm qhov mob hnyav raws li kev soj ntsuam los ntawm KDQOL{ {17}} Cov lus nug khaus kuj muaj cov qhab nia CES-D ntau dua li cov neeg mob uas tau qhia me me lossis tsis muaj pruritus [28]. Kev tshawb nrhiav ntev ntawm 1799 tus neeg mob Nyij Pooj los ntawm J-DOPPS cohort (lub sijhawm ua raws: 0.{{24} }.5years) pom tias cov neeg mob uas tsis muaj lossis mob me me uas qhia tus kheej cov tsos mob ntawm kev nyuaj siab ntawm lub hauv paus muaj feem ntau yuav ua rau mob hnyav rau yav tom ntej, qhia txog qhov muaj peev xwm txuas ntawm ob cov tsos mob no [45]. Lub GEHIS qhia tias cov neeg mob uas muaj pruritus muaj cov qhab nia ntawm kev ntxhov siab ntau dua li cov uas tsis muaj pruritus, raws li kev soj ntsuam los ntawm Tsev Kho Mob thiab Kev ntxhov siab D epression Scale (HADS) tab sis pom tsis muaj qhov sib txawv ntawm cov qhab nias ntawm kev nyuaj siab [20].
Lwm cov tsos mob cuam tshuam nrog cov kab mob raum ntev-kwv yees pruritus
Txoj kev tshawb fawb GEHIS tau pom tias, ntxiv rau kev pw tsaug zog, cov neeg mob CKD-aP feem ntau yuav muaj mob ntau dua li cov uas tsis muaj CKD-aP, thiab qhov no kuj tau ua rau lawv txo qis HRQoL [31]. Soj ntsuam ob txhais ceg thiab pruritus tau tshaj tawm tias feem ntau tshwm sim hauv cov neeg mob ESKD [46", 47].
Muaj peev xwm cuam tshuam los ntawm kev txo qis pruritus ntawm cov tsos mob ntsig txog thiab cov txiaj ntsig kho mob
Cov ntaub ntawv los ntawm cov kev tshawb fawb txog kev kho mob antipruritic qhia tau hais tias kev txo qis ntawm pruritus siv ntawm cov neeg mob nrog CKD-aP tab tom hemodialysis yog txuam nrog kev txhim kho zoo sib xws hauv lawv cov HRQoL [48", 49], thiab txo qis kev siv zog tuaj yeem txhim kho kev pw tsaug zog zoo ntawm cov neeg mob no.
Difelikefalin yog ib qho kev txwv peripheral, xaiv kappa-opioid receptor (KOR) agonist, tsis ntev los no tau pom zoo los ntawm US Food and Drug Administration (FDA) rau kev kho mob ntawm qhov nruab nrab-rau- mob pruritus cuam tshuam nrog CKD hauv cov neeg laus hemodialysis [50"]. Difelikefalin yog thawj daim ntawv tso cai kho mob rau CKD-aP tshwj tsis yog rau nalfurafine hauv Nyij Pooj. Theem 3 qhov kev sim tshuaj tau pom tias lub neej zoo li falin tuaj yeem txo qhov kev mob pruritus thiab txhim kho khaus QoL hauv cov neeg mob uas muaj mob hnyav CKD-aP [ 51", 52", 53"]. Cov kev tshawb fawb no kuj qhia tau hais tias qhov txo qhov khaus kuj tuaj yeem txhim kho kev pw tsaug zog zoo. Kev tshawb fawb txog gabapentin thiab lwm yam tshuaj tiv thaiv khaus khaus yog tawm ntawm qhov kev tshuaj xyuas no vim lawv yog cov kev kho mob uas tsis muaj ntawv tso cai.
Ib 12-lub lim tiam, ib sab caj npab Phase 3 sim (Study 3105) pom tias kev kho mob nrog IV difelikefalin yog txuam nrog kev txhim kho hauv cov neeg mob tau tshaj tawm cov lus nug zoo pw tsaug zog [52"]. Tom qab ntawd qhia tau hais tias cov no tau muaj kev sib raug zoo (r=0.78) nrog kev txo qis hauv kev siv pruritus ntawm Lub Limtiam 12, raws li kev ntsuam xyuas los ntawm kev hloov pauv hauv lub limtiam txhais tau tias tus neeg mob tau tshaj tawm 24-h qhov mob hnyav tshaj qhov ntsuas tus lej ntsuas ( WI-NRS) [54"]. Tsis tas li ntawd, kev tshawb nrhiav kev tshawb fawb ntawm cov ntaub ntawv sib sau los ntawm randomized, placebo-tswj, 12-lub lim tiam, Phase 3 KALM-1 thiab KALM-2 kev sim tshuaj ntawm IV lifelike-falin kuj tau tshaj tawm txog kev sib raug zoo. nruab nrab ntawm kev txo qhov khaus khaus nrog difelikefalin raws li ntsuas los ntawm WI-NRS thiab kev txhim kho hauv kev pw tsaug zog zoo raws li kev ntsuas los ntawm qhov nruab nrab 5-D daim ntawv nug txog kev pw tsaug zog tsis taus cov lus nug [55"].
Ib qho randomized, Theem 3, ob-dig muag, placebo-tswj sim ntawm centrally acting mu-opioid receptor (MOR) antagonist / KOR agonist, nalbuphine, kuj pom tias txo qhov khaus khaus nrog qhov kev kho mob no kuj ua rau kev txhim kho kev pw tsaug zog cuam tshuam rau cov neeg laus hemodialysis. Cov neeg mob nrog CKD-aP [49].
Raws li cov ntaub ntawv tshawb fawb tau piav qhia ua ntej qhia tau hais tias cov neeg mob uas mob hnyav CKD-aP feem ntau yuav thim tawm ntawm kev lim ntshav ntau dua li cov neeg mob uas muaj cov tsos mob me me [6",24]. yog li ntawd txhim kho lawv cov txiaj ntsig kho mob.
TREATMENTOFCHRONICKIDNEY DISEASE-ASSOCIATED PRURITUS: Clinical EVIDENCE RAU DIFELIKEFALIN
Difelikefalin, ib qho peripheral, xaiv KOR agonist, tsis ntev los no tau los ua thawj txoj kev kho mob uas tau pom zoo los ntawm US FDA rau kev kho mob ntawm CKD-aP [50"]. cev [56].
Kev ua tau zoo thiab kev nyab xeeb ntawm IV difelikefalin tau raug soj ntsuam los ntawm ob qho kev tsim qauv zoo sib xws, randomized, placebo-tswj Phase 3 kev sim (KALM-1 thiab KALM-2) uas ua ke sau npe 851 cov neeg laus uas muaj mob nruab nrab-rau- mob hnyav CKD. -aP kev kho mob hemodialysis 【48", 53" 】. IV lifelikefalin ({{1{{20}}}}}.5 ug / kg ntawm lub cev qhuav dej) lossis cov placebo tau tswj hwm tom qab hemodialysis zaug 3 zaug hauv ib lub lis piam rau 12 lub lis piam. Ob qhov kev sim no tau ntsib lawv cov ntsiab lus tseem ceeb uas qhia tau hais tias qhov feem pua ntawm cov neeg mob ua tiav cov txiaj ntsig ntawm kev kho mob (Ntau dua lossis sib npaug rau 3-taw tes) txo los ntawm lub hauv paus hauv txhua hnub 24-h WI-NRS cov qhab nia tau ntau dua nrog difelikefalin vs cov placebo ntawm Lub Ob Hlis 12(KALM-1: 50.0 feem pua vs 27.6 feem pua ; KALM-2: 54.0 feem pua vs 42.2 feem pua )[48",53"].
Kev ua tau zoo ntawm IV difelikefalin rau qhov txo qhov khaus kuj tau soj ntsuam hauv kev soj ntsuam sib koom ua ke ntawm KALM-1 thiab KALM-2 kev sim uas kuj tau soj ntsuam cov txiaj ntsig ntawm kev kho mob ntawm khaus khaus QoL, raws li kev soj ntsuam los ntawm Skindex{ {3}} thiab 5-D itch scale questionnaires [57]. Qhov kev soj ntsuam sib koom ua ke no tau pom tias qhov ua tiav ntawm Ntau dua lossis sib npaug rau 3- taw tes WI-NRS kev txhim kho los ntawm cov hauv paus ntsiab lus tau ntau dua nrog difelikefalin vs placebo txhua lub sijhawm cov ntsiab lus ntawm Lub Limtiam 1 (Fig. 3a).
Qhov feem pua ntawm cov neeg mob uas ua tiav cov txiaj ntsig kev kho mob hauv tag nrho Skindex-10 qhab nia (Ntau dua lossis sib npaug rau 15- txo qis) tau ntau dua nrog difelikefalin vs placebo ntawm Lub Limtiam 4, 10, thiab 12 (Daim duab . 3b), hos cov uas tau ua tiav cov txiaj ntsig kev kho mob hauv tag nrho 5-D khaus qhab nia (Ntau dua lossis sib npaug rau 5-} txo qis) tau ntau dua nrog difelikefalin vs placebo txhua lub sijhawm ntsuas cov ntsiab lus (Fig. 3c ).
Ob qhov KALM-1 thiab KALM-2 cov kev tshawb fawb tau qhib-daim ntawv txuas ntxiv theem uas, cov neeg mob tsim nyog, los ntawm difelikefalin thiab placebo caj npab, tuaj yeem tau txais kev kho mob nrog difelikefalin ntev txog 52 lub lis piam. Kev txheeb xyuas sib koom ua ke ntawm KALM-1 thiab KALM-2 tau pom tias IV difelikefalin tswj tau qhov ua tau zoo ntawm qhov txo qhov khaus thiab txhim kho khaus khaus QoLover 1 xyoo ntawm kev kho mob hauv qhov qhib-daim ntawv txuas ntxiv.
XAIV
Txawm hais tias muaj kev koom tes meej nrog cov txiaj ntsig kev noj qab haus huv tsis zoo thiab txo qis HRQoL, CKD-aP tseem tsis txaus siab, tsis tau tshaj tawm, thiab tsis muaj kev kuaj mob. Kev tshawb fawb tsom mus rau ib qho kev mob tshwm sim tau ua rau muaj kev nce qib tseem ceeb hauv peb txoj kev nkag siab ntawm CKD-aP tab sis cov neeg mob raum tsis tshua muaj tshwm sim nrog ib qho; yav tom ntej ntawm kev tshawb fawb txog kev tswj cov tsos mob yuav tsum tau tsom mus rau kev ntsuas kev sib raug zoo ntawm ntau yam tsos mob, thiab kev cuam tshuam tshwj xeeb, thiab cov txiaj ntsig ntawm tus neeg mob. Cov tsos mob pawg yog cov uas sib koom ib qho kev sib koom ua ke lossis etiology thiab nws txoj kev sib raug zoo ua rau muaj qhov sib txawv thaum piv rau txhua tus neeg cov tsos mob. Nrog cov tswv yim kho tshiab ntawm lub qab ntug, lub tswv yim ntawm cov tsos mob no sawv cev rau lub sijhawm tsis yog rau kev tswj hwm ntawm CKD-aP, tab sis kuj rau tag nrho cov tsos mob uas peb paub tias tseem ceeb rau peb cov neeg mob.