Kev nce qib tshiab hauv Kev Tswj Ntshav Phosphorus hauv Cov Neeg Mob Tsis Dialysis CKD
Dec 23, 2022
Mob raum kab mob-ntaub thiab pob txha metabolic abnormalities (CKD-MBD) yog ib qho ntawm cov teeb meem loj nyob rau hauv cov neeg mob uas muaj kab mob raum ntev (CKD), thiab nws cov kev tswj yog qhov tseem ceeb rau lub sij hawm ntev ntawm cov neeg mob CKD. Xyoo 2019 "Cov Lus Qhia rau Kev Tshawb Fawb thiab Kev Kho Mob Pob Zeb thiab Cov Pob Txha Tsis Zoo hauv Cov Kab Mob Raum Hniav Hauv Suav Teb" tau taw qhia meej tias CKD-MBD yuav tsum tau txo qis qhov tshwm sim ntawm pob txha thiab mob plawv thiab cerebrovascular teeb meem los ntawm kev tswj tus neeg mob cov ntshav ntshav, calcium, phosphorus. cov tshuaj hormone (PTH) thiab lwm yam ntsuas, kom ua tiav lub hom phiaj ntev ntawm kev txhim kho lub neej zoo ntawm cov neeg mob thiab txo kev tuag [1].
Nyem rau Cistanche herba rau mob raum
Kev tswj ntshav phosphorus tau ntev tau suav tias yog qhov txuas tseem ceeb hauv kev tswj hwm ntawm CKD-MBD [2]. Ib nrab ntawm 2022, peb tau caw xibfwb Peng Hui los ntawm Lub Tsev Kho Mob Thib Peb ntawm Sun Yat-sen University los tshuaj xyuas qhov kev nce qib tshiab hauv kev tswj ntshav phosphorus ntawm cov neeg mob uas tsis yog lim ntshav CKD hauv thawj ib nrab xyoo 2022.
1 Hyperphosphatemia yog ib qho kev pheej hmoo ywj pheej rau CKD kev loj hlob thiab cov xwm txheej hauv plawv
Kev soj ntsuam ntawm NEPHRONA cohort kawm|CKD cov neeg mob uas tsis muaj keeb kwm mob plawv yav dhau los|2445 ua
Kev tshawb fawb lub hom phiaj thiab cov txheej txheem: Ib txoj kev tshawb fawb muaj xws li 2445 tus neeg mob nrog CKD theem 3-5D yam tsis muaj keeb kwm mob plawv los ntawm NEPHRONA cohort txoj kev tshawb fawb (950 tus neeg mob hauv theem 3, 612 tus neeg mob hauv theem 4, 195 tus neeg mob hauv theem 5, thiab 688 tus neeg mob ntawm dialysis). Multivariate logistic thiab kev sib tw cov qauv kev pheej hmoo rov qab tsom xam cov txheej txheem tau siv los txheeb xyuas cov kev pheej hmoo ywj pheej rau kev nce qib CKD (2- lub sijhawm soj ntsuam xyoo) lossis cov xwm txheej hauv plawv (CVE) (4- xyoo soj ntsuam sijhawm) [3].
Cov txiaj ntsig: Tom qab 2 xyoos, 301 cov neeg mob tau tsim CKD kev loj hlob, hyperphosphatemia suav txog 34.3 feem pua ntawm CKD kev loj hlob, thiab 7.8 feem pua ntawm cov kev mob uas tsis yog CKD, qhov tsis sib xws (OR) 6.16 [95 feem pua Kev ntseeg siab (CI) 4.{{11} }.68, ib<0.001]; during the 4-year follow-up, 203 patients developed CVE, and hyperphosphatemia accounted for 36% of those with CVE, and 28.3% of those without CVE. OR 2.00 (95%CI 1.49-2.67, P<0.001). Hyperphosphatemia is an independent risk factor for the progression of CKD and the occurrence of CVE. In addition, secondary hyperparathyroidism (SHPT) is also an independent risk factor for the progression of CKD and the occurrence of CVE [3].
Qhov sib txawv ntawm qhov sib txawv (LOSSIS) ntawm theem nrab hyperparathyroidism (SHPT), hypercalcemia, thiab hyperphosphatemia hauv tus qauv logistic ntawm kev mob raum mob. Qauv 1: Kev tshuaj xyuas suav nrog peb qhov sib txawv. Qauv 2: Kho rau hnub nyoog thiab poj niam txiv neej. Qauv 3: Kho rau hnub nyoog, poj niam txiv neej, lub cev qhov hnyav, ntshav qab zib, kub siab, haus luam yeeb, thiab proteinuria.
Cov xwm txheej plawv (CVE) qhov phom sij txaus ntshai (HR) rau theem nrab hyperparathyroidism, hypercalcemia, thiab hyperphosphatemia hauv cov qauv kev pheej hmoo sib tw. Qauv 1: Kev tshuaj xyuas suav nrog peb qhov sib txawv. Qauv 2: Kho rau hnub nyoog thiab poj niam txiv neej. Qauv 3: Kho rau hnub nyoog, poj niam txiv neej, lub cev qhov hnyav, ntshav qab zib, ntshav siab, dyslipidemia, kev haus luam yeeb, theem kab mob raum, thiab 25- qib hydroxyvitamin D.
2 Tsis tuaj yeem txo phosphorus, tab sis tuaj yeem txhim kho cov ntsuas xws li uremic toxins thiab atherosclerotic co toxins hauv cov neeg mob uas tsis yog lim ntshav CKD, thiab muaj feem cuam tshuam nrog kev ua raws cai.
Cov lus qhia pom zoo tias cov neeg mob uas tsis yog lim ntshav CKD yuav tsum tau txais 2D phosphorus txo txoj cai ntawm kev noj haus phosphorus tswj (Kev noj haus) thiab kev xaiv tsim nyog ntawm phosphorus binders (Cov Tshuaj)[1]. Phosphorus-txo cov zaub mov yog lub hauv paus ntawm kev tswj ntshav phosphorus hauv cov neeg mob CKD thiab yog ib qho tseem ceeb ntawm kev txo cov phosphorus hauv cov neeg mob uas tsis tau lim ntshav CKD. Txawm li cas los xij, qhov kev siv yog tag nrho ntawm cov teeb meem, suav nrog kev ua raws cai, ntsuas qhov tseeb ntawm cov ntsiab lus phosphorus hauv cov zaub mov, thiab kev noj zaub mov tsis txaus. , tam sim no muaj kev cuam tshuam me ntsis ntawm kev tswj cov ntshav phosphorus hauv cov neeg mob uas muaj CKD siab heev [1]. Kev tshawb fawb tshiab qhia tau hais tias kev noj zaub mov tsis muaj protein ntau tuaj yeem txhim kho cov cim ntawm uremic toxins thiab atherogenic co toxins hauv cov neeg mob uas tsis yog lim ntshav CKD, thiab muaj feem cuam tshuam nrog kev ua raws.
Kev tshawb fawb txog kev noj zaub mov tsis muaj protein ntau|Cov neeg mob uas tsis yog lim ntshav hnyav CKD|57 cas
Kev tshawb fawb lub hom phiaj thiab cov hau kev: Kev tshawb fawb soj ntsuam suav nrog 57 cov neeg mob uas tsis tau lim ntshav nrog CKD hnyav [kwv yees glomerular filtration rate (eGFR) 6-25 ml/min/1.73m2], muab cov khoom noj muaj protein tsawg (0 .6g protein / kg lub hom phiaj qhov hnyav) rau 2 lub hlis, ntsuas tus neeg mob txoj kev ua raws (adherence) thiab sib xws (concordance), thiab soj ntsuam cov khoom noj muaj feem xyuam nrog cov ntsuas [ntshav lipids, ntshav phosphorus, normalized proteolysis rate (nPCR), thiab lwm yam.], uremic co toxins [tag nrho sulfuric acid Hloov pauv hauv qib p-cresol (PCS) thiab PCS dawb, tag nrho indoxyl sulfate (IS) thiab dawb IS] thiab atherogenic toxin [lipoprotein-associated phospholipase A2 (Lp-PLA2)] [4].
Cov txiaj ntsig kev tshawb fawb: Tom qab 2 lub hlis ntawm kev noj zaub mov tsis muaj protein tsawg, nPCR, ntshav urea nitrogen, tag nrho cov roj cholesterol, thiab triglycerides ntawm txhua tus neeg mob tau txo qis, thaum cov ntshav phosphorus tsis hloov pauv loj; theem ntawm PCS dawb tau txo qis hauv cov neeg tuaj koom; qhov sib xws tau siab Cov qib ntawm Lp-PLA2, tag nrho PCS, PCS dawb thiab tag nrho IS tau txo qis hauv cov neeg mob uas tsis sib xws, thaum qib Lp-PLA2 thiab tag nrho PCS nce hauv cov neeg mob uas tsis sib xws [4].
Kev noj zaub mov tsis muaj protein ntau txhim kho uremic thiab atherogenic co toxins hauv nondialysis CKD cov neeg mob, tab sis tsuas yog hauv cov neeg mob uas muaj kev ua raws cai thiab sib xws.
3 Phosphorus binders
Suav CKD-MBD cov lus qhia pom zoo kom txwv tsis pub siv calcium- thiab phosphate-muaj binders, thiab pom zoo kom tsis-calcium- thiab phosphate-muaj binders ua thawj kab. Tsis yog-calcium-muaj phosphate binders feem ntau siv hauv kev kho mob feem ntau yog sevelamer thiab lanthanum carbonate. Tam sim no, lanthanum carbonate tsis qhia cov neeg mob uas tsis yog lim ntshav hauv Suav teb. Nyob rau hauv thawj ib nrab ntawm lub xyoo no, cov uas tsis yog-calcium-muaj phosphate binders tso tawm cov kev tshawb fawb tseem ceeb nyob rau hauv lub sij hawm ntev prognosis ntawm non-dialysis CKD cov neeg mob. Tom ntej no, peb yuav muab cov Tshuag ib los ntawm ib qho.
3.1 Ob daim ntawv pov thawj tshiab tau ntxiv rau cov txiaj ntsig ntev ntawm sevelamer ntawm cov neeg mob uas tsis yog lim ntshav CKD
PECERA txoj kev kawm｜Prospective, multicenter, qhib cohort kawm｜Non-dialysis CKD theem 4-5|966 cas
Kev tshawb fawb lub hom phiaj thiab cov hau kev: A 3-xyoo yav tom ntej multicenter qhib cohort kawm, suav nrog 966 tsis-dialysis CKD theem 4-5 cov neeg laus, piv nrog calcium thiab/lossis tsis-calcium phosphate binders nyob rau hauv kev pheej hmoo ntawm tag nrho cov-ua rau cov txiaj ntsig kev tuag. 515 tus neeg mob (53 feem pua) tau txais phosphate binders, 37 feem pua tau siv cov calcium uas muaj phosphate binders (n=360), 11 feem pua siv tsis yog calcium phosphate binders (n=111), thiab 5 feem pua tau siv ua ke. ntawm ob qho tib si (n{15}}). =44), ntawm cov sevelamer yog tib qho uas tsis yog-calcium phosphate binder tau sau tseg thaum lub sijhawm kawm.
Cov txiaj ntsig: Cov neeg mob Sevelamer-kho tau muaj qhov txo qis 53 feem pua ntawm tag nrho cov neeg tuag tag nrho [kev phom sij (HR) 0.47, 95 feem pua CI 0.27-0.84], qhov tsis muaj qhov txo qis hauv cov neeg mob kho nrog calcium-phosphate binders (HR {{10}}}.77, 95 feem pua CI 0.57-1.03) [5]. Cov kev tshawb fawb tau pom tias sevelamer tuaj yeem txo qhov kev pheej hmoo ntawm txhua qhov ua rau tuag hauv cov neeg mob uas tsis yog lim ntshav CKD nrog hyperphosphatemia.
Loj retrospective real-world cohort kawm|tsis-dialysis CKD theem 1-5|9047 ua
Kev tshawb fawb lub hom phiaj thiab cov hau kev: Kev tshawb fawb txog kev rov qab los ntawm lub ntiaj teb tiag tiag ntawm 9047 cov neeg laus nrog nondialysis CKD hyperphosphatemia uas tau txais sevelamer los yog calcium-muaj phosphate binders (CPB) tau suav nrog hauv Optum Clinformatics® cov thawj coj thov cov ntaub ntawv hauv Tebchaws Meskas. Rau cov neeg mob, 1: 1 propensity score matching (PSM) txoj kev tau siv los kho qhov sib txawv ntawm qhov sib txawv ntawm cov pab pawg. Tom qab PSM, muaj 2399 tus neeg mob hauv pawg sevelamer thiab CPB pawg, thiab lub sijhawm nruab nrab ntawm kev soj ntsuam yog 1032.1 ± 985.9 hnub. Thawj qhov kawg yog kev kho lub raum (RRT, suav nrog hemodialysis, peritoneal dialysis, thiab hloov lub raum), thiab cov ntsiab lus thib ob yog cov xwm txheej tseem ceeb ntawm cov hlab plawv (MACE, suav nrog txhua qhov ua rau tuag, mob myocardial infarction, mob stroke), MACE ntxiv. (xws li MACE, tsis ruaj khov angina thiab lub plawv tsis ua haujlwm) thiab tag nrho ua rau tuag [6]
Cov txiaj ntsig: Thaum lub sijhawm {{0}} xyoo rov qab, Sevelamer txo qis qhov tshwm sim ntawm RRT hauv cov neeg mob uas tsis yog lim ntshav CKD los ntawm 16 feem pua (HR 0.84, 95 feem pua CI 0. 79-0.91, p<0.001), compared with calcium-phosphate binders. The reduction in the incidence of MACE and MACE+ was 9% (HR 0.91, 95%CI 0.84-0.99, P=0.0249) and 12% (HR 0.88, 95%CI 0.81-0.95, P= 0.0009) respectively [6].
Cov kev tshawb fawb tau pom tias Sevelamer tuaj yeem txo qis kev siv lub raum hloov kho hauv cov neeg mob CKD thiab txo qhov tshwm sim ntawm cov xwm txheej loj hauv plawv.
3.2 Cov txiaj ntsig mus sij hawm ntev ntawm lanthanum carbonate ntawm cov neeg mob tsis lim ntshav CKD tsis tau txais txiaj ntsig zoo
IMPROVE-CKD Kev Kawm｜Multicenter, Randomized Ob-dig muag Tswj Kev sim|CKD Phase 3b~4|278 Cas
Research endpoint: A multi-center, randomized double-blind trial, including 278 patients with CKD stage 3b~4 with blood phosphorus >1. rau 96 w. Primary endpoint is carotid-femoral pulse wave velocity (PWV) [7]. Cov txiaj ntsig kev tshawb fawb ntsig txog tau luam tawm xyoo 2020, thiab xyoo no, qhov kev tshawb fawb tom qab kev tshawb fawb zaum kawg uas siv cov qib calcium protein ntau (CPP) raws li qhov kev tshawb fawb kawg tau tso tawm [8].
Cov txiaj ntsig kev tshawb fawb: Rau cov neeg mob uas tsis tau lim ntshav nrog CKD siab heev nrog cov normophosphatemia, piv nrog cov placebo, tsis muaj qhov sib txawv tseem ceeb hauv PWV thiab ntshav phosphorus qib tom qab 96 lub lis piam ntawm lanthanum carbonate kho[7], thiab tsis muaj kev hloov pauv hauv CPP[8] .
Cov kev tshawb fawb tau pom tias lanthanum carbonate tsis tau txhim kho PWV thiab cov ntshav phosphorus hauv cov neeg mob uas tsis tau lim ntshav, thiab xav tau kev tshawb fawb ntxiv.
Cov ntsiab lus
CKD-MBD yuav tsum tau txo qis qhov tshwm sim ntawm pob txha thiab mob plawv thiab paj hlwb los ntawm kev tswj cov ntshav calcium, phosphorus, PTH, thiab lwm yam kev ntsuas hauv cov neeg mob, kom ua tiav lub hom phiaj ntev ntawm kev txhim kho lub neej zoo ntawm cov neeg mob thiab txo qis. pheej hmoo tuag. Hyperphosphatemia yog tus yuam sij rau kev tswj hwm ntawm CKD-MBD.
Xyoo no, ib txoj kev tshawb fawb tshiab luam tawm hauv Nephrology Dialysis Transplantation ib zaug ntxiv tau lees paub tias hyperphosphatemia yog ib qho kev pheej hmoo ntawm kev pheej hmoo rau CKD kev loj hlob thiab cov kab mob plawv, thiab kev tswj hwm ntawm cov ntshav phosphorus thaum ntxov yuav tsum tau them nyiaj rau hauv kev kho mob.
Cov txiaj ntsig mus sij hawm ntev ntawm phosphorus txwv tsis pub noj zaub mov hauv cov neeg mob uas tsis yog lim ntshav CKD tau muaj teeb meem. Suav CKD-MBD cov lus qhia taw qhia tias kev txwv tsis pub noj phosphorus noj yog ib qho tseem ceeb ntawm kev txo cov phosphorus hauv cov neeg mob uas tsis yog lim ntshav CKD, tab sis raws li cov pov thawj uas twb muaj lawm, nws muaj kev cuam tshuam me ntsis rau kev tswj ntshav phosphorus hauv cov neeg mob CKD siab heev. Thiab xyoo no cov kev tshawb fawb soj ntsuam tshiab tau tshaj tawm ib zaug ntxiv tias rau cov neeg mob uas tsis tau lim ntshav CKD, phosphorus txwv tsis pub noj zaub mov tsis tuaj yeem txo cov ntshav phosphorus, thiab tsuas yog txhim kho uremic toxins thiab atherosclerosis hauv cov neeg mob uas tsis tau lim ntshav CKD nrog kev ua tau zoo thiab sib xws. Toxin tsub zuj zuj. Txoj kev tshawb no qhia tau hais tias hauv peb qhov chaw kho mob yog tias cov neeg mob ua tsis zoo lossis tsis ua raws li xav tau, phosphorus binders yuav tsum tau ntxiv kom sai li sai tau.
Tam sim no cov lus qhia hauv tsev thiab txawv teb chaws pom zoo kom txwv kev siv cov calcium-phosphate binders. Suav CKD-MBD cov lus qhia pom zoo kom tsis muaj calcium uas muaj phosphate binders ua cov tshuaj thawj zaug. Tsis yog-calcium-muaj phosphorus binders feem ntau siv hauv kuv lub teb chaws suav nrog sevelamer thiab lanthanum carbonate. Tam sim no, tsuas yog sevelamer carbonate muaj cov lus qhia rau cov neeg mob uas tsis yog lim ntshav CKD hauv Suav teb. Ob leeg tau tshaj tawm cov kev tshawb fawb tseem ceeb ntawm kev kwv yees ntev ntawm cov neeg mob uas tsis yog lim ntshav CKD xyoo no. Ntawm lawv, ob txoj kev tshawb fawb ntawm sevelamer feem ntau tau lees paub tias piv nrog cov calcium-phosphate binders, nws tuaj yeem txo qhov kev pheej hmoo ntawm txhua qhov kev tuag, kev pheej hmoo nkag mus rau RRT, thiab kev pheej hmoo ntawm cov kab mob plawv hauv cov neeg mob uas tsis tau lim ntshav CKD. IMPROVE-CKD txoj kev tshawb fawb ntawm lanthanum carbonate tseem tsis tau txais txiaj ntsig zoo.
Yog xav paub ntxiv:ali.ma@wecistanche.com
