Vitamin D Thiab Lub raum: Ob Tus Neeg Ua Si, Ib Lub Ntsiab Lus
Oct 27, 2023
1. Taw qhia
Lub denomination "vitamin D" yog hais txog ib pawg ntawm liposoluble, steroidal compounds tseem ceeb heev rau txoj hnyuv nqus thiab rau cov metabolism hauv cov calcium thiab phosphates [1]. Cov isoforms tseem ceeb tshaj plaws hauv tib neeg lub cev yog ergocalciferol (vitamin D2) thiab cholecalciferol (vitamin D3), tseem hu ua calculus; thaum thawj tus tsuas yog synthesized hauv cov nroj tsuag thiab fungi (kev noj haus), qhov thib ob yog ob qho tib si exogenous thiab tsim endogenously los ntawm photolysis ntawm 7-dehydrocholesterol los ntawm UVB hluav taws xob nyob rau hauv daim tawv nqaij [2]. Calciols tau txais ob-kauj ruam hydroxylation kom tig mus rau hauv daim ntawv lom neeg, calcitriol. Ua ntej, vitamin D 25-hydroxylase nyob rau hauv daim siab mediates D2/D3 hloov mus rau 25 (OH)D (calcidiol), ib tug quantifiable daim ntawv feem ntau yog siv los txiav txim vitamin D theem nyob rau hauv cov ntshav, thiab nws yog txhais raws li ib haiv neeg daim ntawv. . Cov kauj ruam tom ntej yog hydroxylation ntawm carbon 1 nyob rau hauv lublub raum proximaltubule los ua calcitriol, kuj hu ua 1,25-dihydroxyvitamin D [1,25(OH)2D]. Serum 1,25 (OH) 2D muab cov ntaub ntawv me me txog vitamin D raws li txoj cai, thiab nws feem ntau yog ib txwm muaj lossis txawm tias nce siab thaum hyperparathyroidism cuam tshuam nrogvitamin D tsis txaus [3].
NYEM QHOV NO RAU CISTANCHE RAUVITAMIN D DEFICIENCY
1,25 (OH) 2D mus txog lub hom phiaj ntawm lub cev los ntawm cov vitamin D-binding protein (VDBP) nyob rau hauv cov kab mob, ces khi rau lub zos vitamin D receptor (VDR). Nws paub tias VDR belongs rau ntau pawg ntawm ligand-activated nuclear transcription yam, thiab nws muaj peev xwm khav tau ib tug yuav luag ubiquitous thiab cov ntaub so ntswg-dependent qhia nyob rau hauv nucleated hlwb [4]. Dhau li ua rau kev nqus, tso zis, thiab txhawb nqa cov calcium thiab phosphorus, vitamin D kuj ua haujlwm ntau yam uas tsis yog-osteogenic thiab tsis yog-calcemic, yog li sawv cev rau tus neeg tseem ceeb hauv kev noj qab haus huv ntawm lub cev [3].
Txhawm rau kom tsis txhob qaug cawv, calcidiol thiab calcitriol raug tswj nruj nruj los ntawm 25 (OH) D 24- hydroxylase (CYP24A1), uas yog thawj vitamin D-inactivating enzyme rau ob lub tebchaw [5]. Ntxiv mus, cov tshuaj parathyroid hormone (PTH) thiab fibroblast kev loj hlob zoo tshaj 23 (FGF23) kuj tswj cov vitamin D metabolism. PTH yog tsim los ntawm cov qog parathyroid thib ob mus rau qib qis calcium hauv cov ntshav; nws ob leeg txhawb cov pob txha tig rov qab thiab upregulates 1,25 (OH) 2D qib vim qhov induction ntawm lub raum qhia ntawm kev koom tes cytochrome tochrome (CYP27B1). FGF23 es tsis txhob yog tsim los ntawm osteoblasts thiab osteoclasts nyob rau hauv cov lus teb rau siab phosphate thiab calcitriol serum qib thiab downregulates calcitriol ntau lawm los ntawm inhibiting CYP27B1 nyob rau hauv lub raum [6,7]. Nyob rau hauv daim duab 1, lub ntsiab systemic nyhuv ntawm 1,25 (OH) 2D ar
Vitamin D hauv pob txha Homeostasis
Vitamin D muaj kev tswj ncaj qha thiab tsis ncaj ntawm cov pob txha-matrix tsim, vim nws lub ntsiab physiological muaj nuj nqi yog kev hloov pauv ntawm calcium thiab phosphorus absorption lossis reabsorption ntawm ntau qib. Nyob rau hauv no ncej, lub raum muaj ib tug loj kev koom tes: ib zaug calcium thiab inorganic phosphorus raug lim mus rau purine, 1,25 (OH) 2D, ua ke nrog PTH, tswj lawv reabsorption los ntawm ntau yam channel thiab transporters nyob rau hauv distal, tubular ntu [8]. Hauv cov xwm txheej ntawm lub raum ua haujlwm ib txwm muaj, kwv yees li 98% ntawm cov calcium lim dej yogreabsorbed nyob rau hauv lub raum; nyob rau hauv cov tubules ze ze, qhov twg thiazide diuretics, 1,25 (OH) 2D, thiab PTH tsis muaj kev cuam tshuam, Na-dependent, paracellular mechanisms kho cov uptake ntawm 50-60% ntawm tag nrho cov load ntawm calcium. Lub voj qis thiab qhov nyias nyias, nce siab ntawm lub voj ntawm Henle tsuas yog lub luag haujlwm me hauv calcium homeostasis. Ntawm qhov tod tes, feem pua tseem ceeb ntawm kev rov ua dua ntawm cov ntxhia lim dej tshwm sim hauv cov tuab, nce siab (20%), tubule distal (10-15%),
nyob thiab kho los ntawm epithelial calcium channels, calbindin, thiab plasma membrane Ca2+ ATPase (ATP2B1) [9–11]. Lwm qhov tseem ceeb ntawm cov vitamin D yog kev txhim kho plab hnyuv calcium thiab phosphorus reabsorption. Qhov no yog qhov tseeb tau pom los ntawm cov vitamin D zoo ntawm cov nyiaj calcium uas nkag mus rau hauv: nrog 25 (OH)D tsis txaus, tsuas yog 10-20% ntawm cov calcium noj zaub mov nws thiaj li nkag mus rau hauv cov hlab ntsha, thaum cov qib txaus ntawm prohormone txhim kho kev nqus. rau 30-40% [12,13]. Ntau qhov cuam tshuam ncaj qha ntawm vitamin D ntawm cov pob txha pob txha tsis paub meej. Txawm li cas los xij, muaj ntau cov pov thawj los qhia tias vitamin D koom nrog hauv cov pob txha-cov ntaub so ntswg.
Lwm qhov tseem ceeb ntawm cov vitamin D yog kev txhim kho plab hnyuv calcium phosphorus reabsorption. Qhov no yog qhov tseeb tau pom los ntawm qhov zoo vitamin D cuam tshuam rau tus nqi ntawm cov calcium uas nkag mus rau hauv lub cev: nrog 25 (OH)D tsis txaus, tsuas yog 10-20% ntawm kev noj zaub mov calcium uas nws thiaj li nkag mus rau hauv cov hlab ntsha, thaum cov qib prohormone txaus. qhov nqus mus rau 30-40%(12,13). Ntau qhov cuam tshuam ncaj qha ntawm vitamin D ntawm cov pob txha pob txha tsis paub meej. Txawm li cas los xij, muaj ntau cov pov thawj los qhia tias cov vitamin D kev koom tes hauv cov pob txha-cov ntaub so ntswg deposition thiab remodeling yog sawv cev tsis tau tsuas yog los ntawm cov kev cai ntawm Ca/P serum qib nrog kev sib raug zoo ntawm PTH tab sis kuj los ntawm kev ncaj qha cuam tshuam rau cov pob txha hlwb. qhia txog VDR, osteoblasts, thiab osteoclasts (14). Txawm hais tias qhov tseeb tias 1a-hydroxylation ntawm (OH)D txog 125(OH)D hauv cov pob txha pob txha tau piav ntau xyoo dhau los, kev tshawb pom ntawm nws cov autocrine / paracrine kev ua haujlwm rau osteoblast thiab osteoclast maturation thiab proliferation yog tsis ntev los no [15]. Nws tau raug pov thawj tias 1,25 (OH) 2D txhawb kev qhia ntawm RANKL, osteocalcin, thiab osteopontin, cuam tshuam nrog osteoblast maturation thiab mineralization. Tsis tas li ntawd, 1,25 (OH) 2D kuj tswj cov kev ua haujlwm siab osteoclastic resorptive thiab txhawb kev qhia ntawm FGF23 thiab sclerostin ntawm VDR [16].
3. Vitamin D nyob rau hauv mob raum kab mob thiab kab mob raum kawg
Cov neeg mob nrogmob raum mob(CKD) thiab kab mob raum kawg (ESRD) muaj ntau duavitamin D tsis txausthiab insufficiency piv rau covcov pejxeem noj qab nyob zoo. Txawv txhais ntawmvitamin D tsis txausthiab kev tsis txaus siab tau muab rau ob peb xyoos dhau los, ua rau muaj cov txheej txheem sib txawv, qhov sib txawv, thiab kev txiav tawm. Txawm li cas los xij, feem ntau cov kws kho mob xa mus rau Endocrine Society cov lus pom zoo, qhov twg 25 (OH)D concentrations < 20 ng / mL txhais tau tias yog qhov tsis txaus, qhov siab ntawm 21 thiab 29 ng / mL raws li qhov tsis txaus, thiab qib ntshav> 30 ng / mL li qub / sufficiency [16]. Muab qhov kev txwv tsis pub noj zaub mov hnyav hauv cov neeg mob lub raum tsis ua haujlwm thiab muaj cov kab mob sib kis uas tuaj yeem cuam tshuam rau kev mus pw hauv tsev kho mob thiab kev txav mus los (ua rau lub hnub raug qis), CKD cov neeg mob feem ntau xav tau cov vitamin D ntxiv, feem ntau yog cholecalciferol thiab calcifediol-based supplements [17]. Ntxiv mus, lub 1 -hydroxylation ntawm 25(OH)D yog impaired vim lub raum puas cov ntaub so ntswg. Qhov tshwm sim hypocalcemia thiab hyperphosphatemia, theem nrab rau lub raum tsis ua haujlwm, ua rau muaj kev cuam tshuam rau theem nrab hyperparathyroidism thiab nce cov ntshav hauv cov ntshav ntawm hyperphosphaturic, osteocyte-derived fibroblast kev loj hlob zoo tshaj 23 (FGF23) [18]. PTH thiab FGF23 muaj qhov cuam tshuam tsis zoo rau kev tswj hwm ntawm 1 -hydroxylase: thaum PTH txhim kho nws cov lus qhia txhawm rau hloov pauv cov calcium poob, FGF23, uas yog tshwm sim los ntawm phosphate retention, inhibits lub raum 1 -hydroxylase qhia [7]. Ntev mus ntev 25 (OH)D thiab 1,25 (OH) 2D insufficiency thiab theem nrab hyperparathyroidism ua rau ib tug dav spectrum ntawm pob txha puas, feem ntau pom nyob rau hauv cov pej xeem CKD/ESRD hu ua mob raum kab mob-mineral thiab pob txha mob (CKD- MBD) [19].
4. Vitamin D thiab CKD-MBD
Protracted 25 (OH)D thiab 1,25 (OH) 2D deficiency ua rau poob ntawm pob txha pob txha pob txha pob txha thiab cov pob txha loj zuj zus, yog li ua rau tus neeg mob muaj ntau yam pob txha, muaj kev pheej hmoo siab dua ntawm cov kab mob pob txha, kev mob hnyav thiab kev tuag. , thiab thaum kawg, nce nqi kho mob [20,21].
Hauv kev xyaum kho mob, ntau lub npe siv los qhia txog CKD cov kab mob ntsig txog pob txha, thiab lawv tuaj yeem suav nrog hauv peb qhov tseem ceeb, cov kab mob pathological: osteoporosis, CKD-MBD, thiab lub raum osteodystrophy [22].
Osteoporosis txhais tau hais tias yog ib qho kab mob ntawm lub cev, lub cev nqaij daim tawv, qhov twg cov pob txha lub zog thiab kev tiv thaiv raug cuam tshuam, thiab yog li, cov neeg mob cuam tshuam muaj kev pheej hmoo siab ntawm pob txha vim qhov txo qis ntawm pob txha pob txha ntom ntom (BMD, cov ntxhia hauv ib square centimeter, qhia raws li g / cm2 ) thiab pob txha zoo (BQ, kev nthuav dav ntawm microarchitecture, mineralization, turnover, thiab microcrack accumululation) [23–28]. Raws li Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb (WHO), "mob pob txha yog txhais tau tias yog BMD uas yog 2.5 tus qauv sib txawv lossis ntau dua qis dua tus nqi nruab nrab rau cov poj niam noj qab haus huv (tus qhab nia ntawm <−2.5 SD)". Qhov thib ob, siab dua qhov pib uas nyob nruab nrab ntawm −1 thiab −2.5 SD piav qhia txog "cov pob txha qis" lossis osteopenia [23].
CKD-MBD yog ib qho kev cuam tshuam ntawm cov ntxhia hauv cov ntxhia, pib los ntawm phosphorus tuav thiab nce qib ntawm FGF23 thiab PTH, ua rau muaj kev cuam tshuam tsis zoo ntawm pob txha pob txha. Tus kab mob yog tus cwj pwm los ntawm kev hloov pauv ntawm tus thawj xibfwb CKD-MBD biomarkers (calcium, phosphorus, vitamin D, thiab PTH) cuam tshuam nrog kev tsis sib xws hauv pob txha hloov pauv, mineralization, thiab ntim (TMV); extraskeletal calcifications; thiab atherosclerosis [29]. Hauv daim duab 2, lub pathogenesis ntawm CKD-MBD yog schematized.
Daim duab 2. CKD-MBD pathogenesis thiab nws cov teebmeem tseem ceeb. FGF23, fibroblast kev loj hlob 23; P, phosphorus; PTH, parathyroid hormone; Ca, calcium
Thaum kawg, lub denomination "lub raum osteodystrophy" piav qhia txog cov duab sib txawv ntawm cov pob txha kab mob uas tuaj yeem kuaj tau hauv CKD los ntawm cov pob txha biopsy [30], raws li kev faib tawm TMV. Hauv qhov no, cov pob txha cortical yog qhov tseem ceeb tshaj plaws [22]. Osteitis fibrosa cystica yog ib qho tseem ceeb ntawm cov kab mob skeletal thiab yog tus cwj pwm los ntawm cov pob txha loj heev uas ua rau cov pob txha fibrous es tsis txhob resistant, lamellar pob txha, uas ua los ntawm cov ntshav siab PTH qib [22]. Hloov pauv, nyob rau hauv cov kab mob adynamic pob txha, cov pob txha tsis tshua muaj tshwm sim, vim txo qis osteoblasts thiab kev ua haujlwm osteoclasts. Lub peev xwm ntawm cov pob txha tso tawm lossis khaws cov calcium yog qhov cuam tshuam, uas ua rau muaj qhov dav ntawm cov calcium ntau ntau [24,25.
Lub physiological concentration ntawm 25 (OH)D muaj inhibitory teebmeem ntawm PTH transcription [28]. Hauv theem nrab hyperparathyroidism, 25 (OH)D muaj kev sib koom ua ke nrog 1,25 (OH) 2D ntawm PTH ntau lawm [28].
Tsis muaj vitamin D (ob leeg 25 (OH) D thiab 1,25 (OH) 2D) muaj ntau heev hauv cov pej xeem CKD. Yav dhau los, kev txheeb xyuas ntu ntu ntawm 825 HD cov neeg mob tau pom tias 78% ntawm pawg neeg muaj vitamin D (25 (OH)D) tsis txaus (<30 ng/mL) and 18% had severe deficiency (<10 ng/mL). Moreover, they demonstrated that 25(OH)D deficiency was associated with increased early mortality [28]. This phenomenon contributes to the development of high PTH levels and the worsening of secondary hyperparathyroidism
Qee qhov kev tshawb fawb tau qhia txog kev sib koom ua ke ntawm dawb 25 (OH)D thiab cov ntshav PTH poob [31]. Txawm li cas los xij, qee qhov lwm tus tsis tau ua tiav cov lus xaus [32]. Qhov tseeb, nws tseem tsis tau paub meej yog tias qib 25 (OH)D tuaj yeem sawv cev rau tag nrho, lom neeg cov vitamin D. Qhov tseeb, cov tshuaj ntawm ob qho tib si cholecalciferol thiab calcifediol muaj txiaj ntsig zoo hauv kev nce tag nrho thiab dawb 25 (OH) D qib thiab yog cuam tshuam nrog ntshav qab zib PTH-qib poob [33]. Hauv cov neeg mob CKD, ntxiv nrog cholecalciferol tau pom qhov nce ntxiv hauv cov ntshav 25 (OH)D concentration thiab txo qis PTH qib thaum piv nrog cov placebo [34]. Tsis ntev los no, Westerberg tau tshaj tawm tias cov koob tshuaj cholecalciferol siab (8000 IU / hnub) hauv cov neeg mob CKD theem 3-4 tiv thaiv kev txhim kho ntawm theem nrab hyperparathyroidism, tsis muaj kev pheej hmoo ntawm hypercalcemia thiab hyperphosphatemia [35].
2017 KDIGO CKD-MBD Cov Lus Qhia qhia tias cov vitamin D tsis txaus yuav tsum raug kho yog tias CKD theem 3 txog 5a, cov neeg mob uas tsis tau mob ntshav qab zib muaj qhov nce qib lossis tsis tu ncua PTH qib [19]. Kev tswj hwm vitamin D tuaj yeem suav hais tias yog kev kho mob ntxiv rau kev tiv thaiv kev tiv thaiv hyperparathyroidism theem nrab vim tias qhov muaj ntau ntawm cov vitamin D tsis txaus hauv cov pej xeem thiab hauv cov neeg mob CKD. Ntxiv mus, vitamin D muaj ntau yam pleiotropic thiab cov kab mob, raws li tau piav qhia saum toj no. Txawm hais tias muaj pov thawj ntxiv txhawb nqa cov txiaj ntsig ntawm kev pib vitamin D supplementation kom txo qis kev loj hlob ntawm theem nrab hyperparathyroidism, kev ua haujlwm ntawm vitamin D kev tswj hwm rau lub hom phiaj no tseem xav tau ntau qhov kev sim, tswj kev sim los ua pov thawj.
5. Cov nyhuv ntawm Vitamin D Therapy
Vim lub neej ntev ntawm complex 25(OH)D thiab cov vitamin D-binding proteins (15 hnub), txhua hnub, txhua lub limtiam, los yog txhua hli kev tswj hwm yuav ua tau zoo rau kev rov qab 25 (OH)D qib [18,36,37] .
Tam sim no, tsis muaj pov thawj tam sim no xav tau ib qho kev tsim cov vitamin D ntau dua lwm qhov hauv CKD, thiab tsis muaj pov thawj tau pom los ntawm kev txheeb xyuas cov txiaj ntsig uas tau txais los ntawm kev sib xyaw khoom noj khoom haus (ergocalciferol, cholecalciferol, thiab calcifediol) thiab activated vitamin D (VDRAs, calcitriol, thiab paricalcitol) [14]. Cov ntawv tshaj tawm tshiab qhia tau hais tias hauv cov neeg mob CKD, cov khoom noj khoom haus ntawm cov vitamin D muaj kev ua haujlwm tsis zoo ntawm PTH thiab cov vitamin D ntxiv tsis zoo rau VDRAs rau kev kho mob hyperparathyroidism, tshwj xeeb tshaj yog nyob rau hauv cov neeg mob dialysis [14,27]. Txawm li cas los xij, cholecalciferol supplementation hauv cov neeg mob lim ntshav ua rau muaj kev nce ntxiv ntawm 25 (OH) D thiab 1,25 (OH) 2D, qhia tias kev ua haujlwm ntxiv rau lub raum yuav yog qhov tseem ceeb hauv cov neeg mob no [14]. Cov kev cuam tshuam no nyob ntawm qhov ntau npaum li cas ntawm cov vitamin D, hom vitamin D compounds, lub sijhawm ntawm txoj kev tshawb fawb, thiab cov neeg soj ntsuam.
Kandula et al. qhia tias kev noj haus vitamin D ua rau kom nce 25 (OH) D qib tsis cuam tshuam cov calcium thiab phosphorus qib tab sis ua rau txo qis hauv cov ntshav PTH (41%), feem ntau hauv cov neeg mob ntshav qab zib [38–40]. Jean et al. tau piav qhia txog qhov txiaj ntsig zoo ntawm kev ua haujlwm 25 (OH)D ntxiv rau lub sijhawm ua ntej lim ntshav txhawm rau tiv thaiv kev sib kis hyperparathyroidism (SHPT) [41].
Hais txog cov zaub mov metabolism, vitamin D tau qhia ntau yam teebmeem uas cuam tshuam rau lub raum tsis ua haujlwm thiab kab mob plawv. Kev tswj hwm qib siab cholecalciferol zoo li ameliorate cov hlab plawv thiab endothelial tsis nyob rau hauv cov menyuam yaus uas muaj CKD, ntsuas los ntawm kev ntws-mediated dilatation, arterial stiffness, thiab plasmatic ntau npaum ntawm homocysteine thiab von Willebrand [42]. Txawm li cas los xij, Karakas et al. tau lees paub tias kev tswj hwm ntawm cholecalciferol txhim kho qhov feem pua ntawm cov dej ntws tawm hauv cov neeg mob hauv kev kho mob ntshav qab zib [43].
Hauv cov neeg mob ntshav qab zib CKD siv angiotensin-hloov enzyme inhibitors, qhov txo qis hauv proteinuria los ntawm kev ntxiv cov vitamin D ib txwm tau piav qhia [44]. Ib qho RCT los ntawm Meireless et al. qhia tau hais tias cholecalciferol txhawb kev txhawb nqa ntawm CYP27B1 thiab VDR qhia hauv monocytes thiab txo cov ntshav IL-6 thiab C-reactive protein ntau [45]. Hauv kev tshuaj ntsuam meta tsis ntev los no, Mann et al. tsis pom qhov cuam tshuam tseem ceeb ntawm vitamin D ntxiv rau kev tuag [46].
Hauv xyoo 2014, Cochrane tsom xam pom qee cov pov thawj tias vitamin D yuav txo tau tag nrho cov neeg tuag thiab mob qog noj ntshav hauv cov neeg laus. Kev ua kom cov calcium uas tso zis ntau dhau, lub raum tsis txaus, mob qog noj ntshav, thiab mob plawv, plab hnyuv, puas siab puas ntsws, lossis cov tawv nqaij tsis zoo tsis raug txheeb xyuas los ntawm kev ntxiv vitamin D [47].
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