Cov Yam Tseem Ceeb Thiab Qhov cuam tshuam nrog rau lub raum Mineralization hauv Cov Kab Mob Raum Raum Hauv Miv
Jul 24, 2023
TSAB NTAWV
1. Keeb kwm
Nephrocalcinosis yog ib yam kab mob ntawm lub raum mob (CKD). Nws qhov cuam tshuam rau cov kab mob pathophysiological rau miv nrog CKD tsis tau tshawb nrhiav.
2. Lub hom phiaj
Txheeb xyuas nephrocalcinosis uas yuav muaj feem cuam tshuam thiab ntsuas lawv cov kev cuam tshuam ntawm CKD kev vam meej thiab tag nrho cov neeg tuag.
3. Tsiaj
Tsib caug-ib euthyroid cov neeg siv khoom muaj miv nrog International Renal Interest Society (IRIS) theem 2-3 azotemic CKD.
4. Cov txheej txheem
Kev tshawb nrhiav kev sib koom ua ke. Histopathological raum seem raug soj ntsuam rau nephrocalcinosis (von Kossa stain). Nephrocalcinosis qhov hnyav tau txiav txim siab los ntawm kev txheeb xyuas duab (ImageJ). Ordinal logistic regressions tau ua los txheeb xyuas cov teeb meem nephrocalcinosis. Kev cuam tshuam ntawm nephrocalcinosis ntawm CKD kev nce qib thiab kev pheej hmoo tuag tau raug soj ntsuam siv cov qauv sib xyaw ua ke thiab Cox regression, feem. Cov miv tau muab faib los ntawm lawv tus tswv-qhia txog lub sijhawm nruab nrab ntawm phosphate-restricted diet (PRD) noj, qhov twg PRD suav nrog Ntau dua lossis sib npaug li 50 feem pua, 10-50 feem pua, lossis tsis muaj cov khoom noj.
5. Cov txiaj ntsig
Nephrocalcinosis tau ntsuas me me-rau- mob hnyav hauv 78.4 feem pua thiab tsis tuaj-rau-tsawg kawg hauv 21.6 feem pua ntawm cov neeg mob. Siab dua hauv cov ntshav plasma tag nrho cov calcium concentration (tCa; odds ratio [OR]=3.07 per 1 mg/dL; P=.02) thiab noj PRD (10 feem pua -50 feem pua : LOS YOG=8.35; P=.01; Ntau dua lossis sib npaug li 50 feem pua : LOSSIS {{20 }}.47; P=.01) yog ywj siab nephrocalcinosis yam uas yuav muaj. Cov miv uas tsis tuaj yeem-rau-tsawg nephrocalcinosis tau nce plasma creatinine (0.250 ± 0.074 mg / dL / hli; P=.002), urea (5.06 ± 1.82 mg / dL / hli; P=. 01), thiab phosphate (0.233 ± 0.115 mg / dL / hli; P=.05) ntau dua 1 xyoos, thiab muaj lub sij hawm ciaj sia luv luv dua li cov miv uas muaj mob nephrocalcinosis me me.
6. Kev xaus thiab kev kho mob tseem ceeb
Ntau dua plasma tCa ntawm CKD kev kuaj mob thiab kev noj PRD yog nws tus kheej cuam tshuam nrog nephrocalcinosis. Txawm li cas los xij, nephrocalcinosis tsis cuam tshuam nrog kev loj hlob ntawm CKD hauv miv.
Nyem qhov no kom paub seb qhov cuam tshuam ntawm Cistanche ntawm raum yog dab tsi
KEYWORDS
calcification, CKD-MBD, hypercalcemia, nephrocalcinosis.
Taw qhia
Kev cuam tshuam hauv cov ntxhia thiab cov pob txha metabolism muaj nyob hauv cov miv uas muaj kab mob raum (CKD), txawm tias nyob rau theem pib ntawm tus kab mob.1,2 Lub raum ua lub luag haujlwm tseem ceeb hauv calcium thiab phosphate homeostasis. Kev txo qis hauv kev ua haujlwm nephrons hauv CKD ua rau muaj phosphate retention, 3 stimulating phosphaturic hormones, fibroblast growth factor 23 (FGF23), thiab tom qab ntawd parathyroid hormone (PTH), kom tswj lub cev plasma phosphate concentrations. 4-6 Txawm li cas los xij, tsis yog xwb. puas qhov kev hloov pauv no cuam tshuam rau calcium metabolism hauv kev tswj hwm tab sis kuj tseem txhim kho pob txha. Thaum qhov kev hloov pauv no thaum kawg tsis tuaj yeem tiv thaiv plasma phosphate concentration los ntawm kev nce, nws txhawb ectopic calcification. Cov lus teb hloov kho no raug xa mus rau cov kab mob raum tsis zoo-mineral thiab pob txha (CKD-MBD).
Nephrocalcinosis yog tus cwj pwm los ntawm tubulointerstitial calcium phosphate (CaP) lossis calcium oxalate (CaOx) crystal deposition, 8 nyob rau hauv tib neeg yuav luag tsuas yog nyob rau hauv lub raum medulla.9 txheej txheem no pib los ntawm Randall's plaques tsim nyob rau hauv lub raum papillae, uas ua raws li ib tug nadir rau kev loj hlob calification. .9,10 Kev soj ntsuam ntawm qhov tshwm sim ntawm lub teeb microscopy yog lub npe hu ua microscopic nephrocalcinosis (xa mus rau qhov no li nephrocalcinosis).8,11 Cov ectopic calcification tuaj yeem piav qhia, ib feem, los ntawm calcium thiab phosphate ntsev precipitating los ntawm supersaturated kua thaum cov khoom calcium phosphate. (CaPP) tshaj cov khoom solubility. Cov kev tshawb fawb yav dhau los tau qhia tias kev nce qib hauv cov ntshav phosphate concentration thiab CaPP sib raug zoo nrog rau lub raum calcium cov ntsiab lus, 12,13 thiab nce ntshav calcium concentration yog ib qho kev pheej hmoo ntawm nephrocalcinosis hauv tib neeg cov neeg mob CKD.11 Nephrocalcinosis muaj nyob rau hauv tib neeg thiab miv nrog CKD.14, 15 Lub raum calcium deposition tau pom nyob rau hauv histology hauv ntau dua lossis sib npaug li 50 feem pua ntawm cov miv nrog International Renal Interest Society (IRIS) Theem 2 txog 4, piv rau 21 feem pua ntawm cov miv uas tsis yog azotemic.15 Hauv vivo hauv nas, lub raum calcium cov ntsiab lus tau cuam tshuam tsis zoo nrog creatinine tshem tawm, qhia txog kev cuam tshuam rau lub raum ua haujlwm.13,16
Miv nrog CKD muaj kev pheej hmoo ntau ntxiv ntawm kev tsim cov ntshav plasma tag nrho hypercalcemia, nrog kev nce ntxiv nrog kev nce qib azotemia.17 Hauv CKD miv noj cov zaub mov txwv tsis pub phosphate (PRD), nce ntshav phosphate thiab tag nrho cov calcium (tCa) concentrations cuam tshuam nrog CKD kev loj hlob. 18 Txawm li cas los xij, tseem yuav txiav txim siab seb calcium thiab phosphate homeostasis dysregulation ua lub luag haujlwm hauv nephrocalcinosis pathogenesis. Tsis tas li ntawd, qhov cuam tshuam ntawm nephrocalcinosis cuam tshuam nrog CKD hauv miv tsis tau tshawb xyuas. Peb lub hom phiaj kev tshawb fawb yog: (a) tshawb nrhiav qhov muaj feem cuam tshuam rau nephrocalcinosis hauv CKD miv thiab (b) soj ntsuam cov koom haum ntawm nephrocalcinosis nrog kev hloov pauv hauv CKD-MBD tsis, CKD kev loj hlob, thiab tag nrho cov neeg tuag.
Cistanche tubulosa
Txoj kev
1. Case xaiv
Cov ntaub ntawv ntawm 2 London-raws li kev xav thawj zaug ntawm 1 Lub Ib Hlis 1992 thiab 31 Lub Kaum Ob Hlis 2017 tau raug tshuaj xyuas thiab azotemic CKD miv uas tau ua tiav kev kuaj mob necropsy raug txheeb xyuas. Kev kuaj mob Azotemic CKD tau txhais tias yog plasma creatinine concentration ntau dua lossis sib npaug li 2 mg / dL nrog cov zis tshwj xeeb gravity (USG)<1.035, or plasma creatinine concentration ≥2 mg/dL on 2 consecutive occasions 2-4 weeks apart without evidence of a pre-renal cause. All cats with a CKD diagnosis were offered a PRD. A variety of PRD was used throughout the study (Feline Low Protein Diet [wet]; Masterfoods, Bruck, Austria; Waltham Veterinary Diet, Feline Low Phosphorus Low Protein [dry and wet]; Effem, Minden, Germany [dry] and Masterfoods, Bruck, Austria [wet]; Feline Veterinary Diet Renal [dry and wet], Royal Canin SAS, Aimargues, France [dry] and Masterfoods, Bruck, Austria [wet]) with a phosphorus content of 0.7-1.1 g/Mcal and calcium-to phosphorus ratio (Ca:P) of 1.3-2.1. Cats not accepting a PRD continued on their maintenance diets.
Inclusion required a formalin-fixed paraffin-embedded (FFPE) kidney block for histopathological evaluation. Cats were excluded if they had clinically suspected hyperthyroidism and their plasma total thyroxine (TT4) concentration was >40 nmol / L, lawv tau raug tswj hwm kho mob rau hyperthyroidism, muaj pov thawj ntawm lwm yam kab mob sib xws, lossis raug kho nrog corticosteroids, furosemide, lossis bisphosphonates. Miv nrog IRIS CKD theem 4 ntawm kev kuaj mob thiab cov miv uas tsis muaj kev mus ntsib tom qab kuaj CKD kuj raug cais tawm. Cov miv tau txais amlodipine besylate rau kev mob ntshav siab tau suav nrog.
2. Clinicopathological cov ntaub ntawv
Cov ntshav, zis, thiab cov qog nqaij hlav necropsy tau sau nrog tus tswv kev pom zoo thiab Royal Veterinary College Ethics thiab Welfare Committee pom zoo (URN20131258E). Cov ntshav kuaj tau sau los ntawm jugular venipuncture rau hauv heparinized thiab ethylenediaminetetraacetic acid (EDTA) hlab thiab zis tau los ntawm cystocentesis. Cov qauv raug khaws cia ntawm 4 C rau<6 hours before centrifugation and separation. Heparinized plasma was analyzed biochemically at an external laboratory (IDEXX laboratories, Wetherby, UK). Inhouse urinalyses, including USG measurement by refractometry, dipstick chemical analysis, and microscopic urine sediment examination, were performed on the day of collection. Urinary tract infection was confirmed by bacterial culture (Royal Veterinary College Diagnostic Laboratory Services, Hatfield, UK).
Systolic blood pressure (SBP) measurements were made as previously described by Doppler.19 Indirect ophthalmoscopy was performed using a retinal camera (ClearView, Optibrand, Fort Collins, Colorado) in cats with an average SBP >160 mm Hg. Systemic hypertension was defined as an average SBP >160 mm Hg in conjunction with ocular pathology consistent with hypertensive damage, or SBP >170 mm Hg ntawm 2 lub sijhawm sib law liag.
Clinical records were reviewed to extract the following: age, sex, breed, body weight, SBP, tCa, ionized calcium (iCa), plasma creatinine, urea, phosphate, potassium, sodium, chloride, total protein, albumin, and TT4 concentrations, plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, PCV, USG, and urine culture results. The proportion of PRD recorded as being fed at every visit (until death) from each cat with PRD prescribed after CKD diagnosis was reviewed from our clinical records. Owners were asked at each visit to estimate the proportion of PRD by volume of the total quantity of food fed. A time-averaged proportion of PRD fed by volume of the total ration was calculated from this estimate for each cat. Where the proportion fed was missing from the record at a particular visit, the proportion stated at the previous visit was imputed, except if it was the visit at which euthanasia was recommended and the cat had deteriorated clinically from the previous visit. Cats were categorized according to the time-averaged ingestion of PRD, where PRD comprised ≥50%, >10 feem pua,<50%, or none of their food intake for their CKD duration.
Cistanche ntxiv
3. Cov ntaub ntawv histopathological
Kev kuaj mob necropsy tau muab rau txhua tus neeg siv khoom thaum lawv cov miv tau euthanized thiab tau txais kev pom zoo los ntawm cov neeg pom zoo. Ntawm necropsy, txhua lub raum tau muab faib ua longitudinally thiab transversely thiab ruaj khov (10 feem pua ntxhiab buffered formalin). Formalin-taw lub raum cov ntaub so ntswg (xws li cortex thiab medulla) yog paraffin-embedded rau yav tom ntej histopathological kev ntsuam xyuas. Ib 4-μm ntu ntawm FFPE cov ntaub so ntswg tau stained nrog von Kossa los txheeb xyuas hydroxyapatite deposits.20 Stained sagittal raum seem tau duab, dig muag rau cov ntaub ntawv, siv lub tshuab ntsuas digital (Leica DM4000, Wetzlar, Lub teb chaws Yelemees) rau kev soj ntsuam microscopic nephrocalcinosis (Daim duab 1). ImageJ (Version 2.1.0, National Institutes of Health, Bethesda, Maryland) tau siv los txheeb xyuas cov kab mob nephrocalcinosis los ntawm cov duab sawv cev raug ntes ntawm thaj tsam medullary. Nephrocalcinosis tau muab qhab nia raws li qhov nruab nrab ntawm cov ntaub so ntswg zoo los ntawm 5 medullary dluab ntes ntawm 10 magnification. Lawv tau muab qhab nia raws li hauv qab no:<0.06% = grade 0, 0.06% to 1% = grade 1, and >1 feem pua = qib 2 (Daim duab 1). Qhov kev muab qhab nia no, txiav txim siab ua ntej ua ntej kev txheeb xyuas, muab lub hom phiaj kom muaj nuj nqis ntawm nephrocalcinosis qhov hnyav (0.06 feem pua thiab 1 feem pua yog sib npaug rau 1 10 5 cm2 thiab 1.4 10 4 cm2, feem). Ib ntu FFPE uas nyob ib sab ntawm txhua rooj plaub tau stained nrog Alizarin liab (ntawm pH 4.2), tso cai rau CaP thiab CaOx crystal sib txawv.20
FIGURE 1 Lub raum, von Kossa stain, x10 magnification. Ib qho piv txwv ntawm txhua qib nephrocalcinosis (0-2) yog qhia raws li nram no: (A) thiab (B) miv tsis. 7 nrog qib 0 nephrocalcinosis (0.004 feem pua ); (C) thiab (D) cat no. 34 nrog qib 1 nephrocalcinosis (0.327 feem pua); (E) thiab (F) cat no. 39 nrog qib 2 nephrocalcinosis (5.51 feem pua). Von Kossa zoo staining yog piav qhia hauv cov xim dub hauv cov duab qub (A, C, thiab E), lossis ci liab tom qab ua tiav siv ImageJ (B, D, thiab F; 8- xim xim; pib 0-92 }) rau qhov kom muaj nuj nqis ntawm thaj tsam ntawm nephrocalcinosis hauv txhua kis (n=51)
4. Micro-computed tomography (micro-CT) rau macroscopic nephrocalcinosis
FFPE lub raum blocks tau raug tshuaj xyuas rau macroscopic nephrocalcinosis siv micro-computed tomography (CT) scanner (Skyscan 1172, Bruker, Kontich, Belgium) siv lub koob yees duab me me (4000 x 2672 pixels) yam tsis muaj lim. Cov duab tau txais los ntawm kev siv cov kev ntsuas hauv qab no: isotropic voxel loj 5 μm ib pixel, qhov hluav taws xob 50 kV, qhov chaw tam sim no 200 μA, lub sijhawm raug 670 ms, thiab imaging rotation scan 180 nrog 0.4 rotation kauj ruam. Projection dluab tau reconstructed rau hauv tomograms siv NRecon 1.7.5.9 (Bruker, Kontich, Belgium) thiab repositioned siv Dataviewer 1.5.6.6 (Bruker, Kontich, Belgium). Tomograms tau txheeb xyuas siv Bruker tsom xam software CT-Analyzer (CTAn) 1.20.3 (Bruker, Kontich, Belgium) thiab ntim-rendered 3-dimensional (3D) visualizations tau tsim siv CTVox 3.3 (Bruker Kontich, Belgium). Luv luv, rau txhua qhov thaiv, cov ntaub so ntswg ntim tau suav los ntawm kev sib npaug ntawm qhov tob los ntawm thaj tsam nruab nrab ntawm 5 tomograms spaced ntawm qhov sib npaug sib npaug thoob plaws hauv cov qauv; nephrocalcinosis ntim tau suav nrog 3D tsom xam cov cuab yeej hauv CTAN. Lub nephrocalcinosis ntim-rau- raum cov ntaub so ntswg piv (VN: KT) tau suav nrog cov qauv:
5. Kev txheeb cais
Kev txheeb xyuas txheeb cais tau ua tiav siv R software (Version 4.1.1 GUI 1.77 High Sierra tsim, R Foundation for Statistical Computing, Vienna, Austria). Hom I yuam kev tus nqi tau teeb tsa ntawm .05. Cov kev hloov pauv tsis tu ncua tau raug ntsuas rau qhov qub los ntawm kev tshuaj xyuas qhov muag ntawm histograms thiab siv Shapiro-Wilk test. Levene qhov kev sim tau siv los ntsuas yog tias cov pab pawg muaj qhov sib npaug sib npaug. Feem ntau cov ntaub ntawv tsis raug faib tawm thiab yog li cov ntaub ntawv xov tooj tau nthuav tawm raws li qhov nruab nrab (25th, 75th feem pua) rau qhov sib xws. Cov ntaub ntawv categorical raug nthuav tawm raws li feem pua.
5.1 Nephrocalcinosis muaj feem cuam tshuam
Cov kev hloov pauv hauv paus tau muab piv los ntawm cov pab pawg los ntawm 1-txoj kev tsom xam ntawm qhov sib txawv (ANOVA) ua raws li Tukey posthoc xeem los yog Kruskal-Wallis thiab Dunn's posthoc xeem rau qhov sib txawv tsis tu ncua nrog kev faib tawm ib txwm lossis skewed, feem. Feem ntau ntawm cov txiaj ntsig categorical tau muab piv nrog Fisher qhov kev ntsuas tseeb.
Baseline microscopic nephrocalcinosis cov kev pheej hmoo raug soj ntsuam siv cov txheej txheem logistic regression. Hnub nyoog, lub cev hnyav, tCa, creatinine, urea, phosphate, potassium, sodium, chloride, tag nrho cov protein, albumin, ALT, ALP, PCV, USG, thiab CKD lub sij hawm ciaj sia tau nkag mus rau qhov sib txawv tsis tu ncua, qhov sib deev thiab feem ntawm PRD noj ( "Tsis noj PRD" vs "Nyob 10 feem pua -50 feem pua PRD" vs "Ntau dua los yog sib npaug rau 50 feem pua PRD") tau nkag mus ua categorical variables rau univariable analyses. Cov kev hloov pauv uas cuam tshuam nrog nephrocalcinosis ntawm P < .10, thiab nrog cov ntaub ntawv muaj tsawg kawg yog ib nrab ntawm cov miv (n> 25), tau nkag mus rau hauv cov qauv sib txawv. Kev tuav rov qab tshem tawm tau siv los ua kom tau tus qauv kawg nrog P < .05. Ordinal version of the Hosmer-Lemeshow test tau siv los ntsuas qhov kawg qauv qhov zoo-ntawm-haum, thiab muaj kev sib koom ua ke ntawm cov kev pheej hmoo tseem ceeb ntawm kev ywj pheej (P < .05) tau soj ntsuam los ntawm qhov sib txawv ntawm qhov nce nqi. Cov seem rau cov khoom seem thiab cov kev soj ntsuam muaj txiaj ntsig tau tshawb xyuas los ntawm Quantile-Quantile zaj duab xis tshuaj xyuas. Ib qho kev sib raug zoo ntawm qhov kev kwv yees tas mus li thiab cov logit tau soj ntsuam los ntawm categorizing cov hloov pauv mus rau qhov sib npaug ntawm "qis," "nruab nrab," thiab "siab" hauv kev tshawb xyuas logistic regression thiab ntsuas qhov nce lossis txo qis ntawm cov coefficient. Cov txiaj ntsig tau tshaj tawm raws li qhov tsis sib xws (LOSSIS; 95 feem pua kev ntseeg siab lub sijhawm [CI]).
5.2 Kev hloov pauv hauv CKD-MBD tsis dhau sijhawm txog nephrocalcinosis
Cov qauv sib xyaw ua ke tau siv los ntsuas cov kev hloov pauv hauv cov kev hloov pauv hloov pauv mus tas li hauv lub sijhawm. Cov ntaub ntawv ntev los ntawm txhua qhov kev mus ntsib hauv thawj 365 hnub tom qab kuaj mob CKD suav nrog rau cov hauv qab no: lub cev hnyav, tCa, creatinine, urea, phosphate, potassium, sodium, chloride, tag nrho cov protein, albumin, ALT, ALP, thiab PCV. Pab pawg ("qib 0" vs "qib 1" vs "qib 2"), lub sij hawm (hauv lub hlis [30.4 hnub]), thiab kev sib cuam tshuam ntawm pab pawg thiab lub sijhawm raug kho raws li qhov cuam tshuam ruaj khov. Txhua tus miv tus lej thiab lub sijhawm zes nyob rau hauv ib tus miv tau suav nrog 2 qhov cuam tshuam tsis sib xws. Cov seem raug suav tias yog kev ywj pheej hauv cov qauv, thiab kev kuaj xyuas qhov qub. Tsis tau sim los impute cov ntaub ntawv uas ploj lawm. Cov txiaj ntsig tau tshaj tawm raws li coefficient ( ) ± SE.
5.3 Kev koom tes ntawm nephrocalcinosis thiab lwm yam kev muaj sia nyob
Hnub tim ntawm azotemic CKD kev kuaj mob tau txhais tias yog lub hauv paus, qhov kev tuag ntawm txhua qhov ua rau yog qhov xwm txheej ntawm kev txaus siab. Lub sij hawm ciaj sia taus tau piav qhia nrog Kaplan-Meier nkhaus thiab tau muab piv nrog cov pab pawg uas siv qhov ntsuas ntsuas ntsuas thiab Kruskal-Wallis nrog Dunn's posthoc xeem vim tias txhua tus miv tau mus txog qhov kawg ntawm kev kawm. Lub hauv paus hloov pauv uas cuam tshuam nrog kev muaj sia nyob tau tshawb nrhiav siv Cox proportional hazard analysis. Martingale residuals tau siv los ntsuas qhov kev xav ntawm linearity ntawm qhov sib txawv tsis tu ncua hauv Cox qauv. Cov khoom seem rau cov khoom seem thiab cov kev soj ntsuam muaj txiaj ntsig tau tshawb xyuas los ntawm Quantile-Quantile zaj duab xis kev tshuaj xyuas. Cov kev hloov pauv tsis tu ncua tau hloov pauv mus rau hauv categorical variables raws li cov tertiles (hnub nyoog, sodium) yog tias qhov kev xav ntawm kev txaus ntshai, raws li kev soj ntsuam ntawm Kaplan-Meier nkhaus, thiab kev ntsuas kev ywj pheej ntawm txhua qhov sib txawv thiab lub sijhawm tsis tau ntsib. Cov kev hloov pauv uas cuam tshuam nrog kev muaj sia nyob nrog P < .10 hauv kev txheeb xyuas qhov tsis sib xws tau nkag mus rau hauv ntau tus qauv Cox. Qhov kawg Cox regression qauv tau muab los ntawm phau ntawv rov qab tshem tawm nrog P < .05. Cov txiaj ntsig tau tshaj tawm raws li kev phom sij (HR; 95 feem pua CI).
5.4 von Kossa nrog Alizarin liab staining correlation thiab macroscopic nephrocalcinosis
Rau txhua kis, qhov sib npaug ntawm thaj chaw nephrocalcinosis nyob rau hauv lub raum medulla ntawm X 2.5 magnification, raws li stained los ntawm von Kossa thiab Alizarin liab nyias, raug xam. Kev sib raug zoo ntawm 2 cov txheej txheem staining rau microscopic nephrocalcinosis tau soj ntsuam siv Spearman qhov sib txheeb. Hauv ib pawg ntawm 49 tus neeg mob, macroscopic nephrocalcinosis tau soj ntsuam siv micro-CT. Spearman txoj kev sib raug zoo yog siv los ntsuas qhov kev sib raug zoo ntawm proportional nephrocalcinosis ntim (micro-CT) thiab proportional nephrocalcinosis cheeb tsam (von Kossa, txheej txheem cej luam X 0.14- X 0.36 magnification).
Cistanche extract
Kev sib tham
Peb cov txiaj ntsig tau qhia tias qhov siab dua hauv cov ntshav ntshav tCa concentration thiab PRD ingestion yog ywj siab ntawm nephrocalcinosis cov yam ntxwv. Cov miv uas muaj qib 0 nephrocalcinosis tau cuam tshuam nrog nce ntshav creatinine, urea, thiab phosphate concentrations thawj 365 hnub tom qab kuaj azotemic CKD. Cov pab pawg ntawm cov miv no tseem muaj lub sijhawm muaj sia nyob luv dua piv rau cov neeg uas muaj nephrocalcinosis hnyav dua (qib 1 thiab 2). Ib qho tseem ceeb ntawm kev ywj pheej zoo ntawm kev noj zaub mov phosphate txwv thiab kev ciaj sia tau pom.
Lub raum mineralization yog ib tug complex txheej txheem thiab multifaceted thiab nws pathogenesis nyob rau hauv koom nrog CKD tseem tsis meej. Txawm li cas los xij, cov pov thawj nce ntxiv qhia tias kev cuam tshuam cov ntxhia hauv cov metabolism, tshwj xeeb tshaj yog calcium, thiab phosphate, yuav ua rau nephrocalcinosis.11,12 Hauv peb txoj kev tshawb fawb, ntau dua plasma tCa ntawm CKD kev kuaj mob, txawm tias tCa nyob rau hauv lub sij hawm siv, yog ib qho kev pheej hmoo ntawm nephrocalcinosis. yam; tsuas yog 1 (2 feem pua) miv muaj tag nrho cov hypercalcemia ntawm lub hauv paus. Qhov kev tshawb pom no qhia tau tias muaj kev cuam tshuam me me hauv calcium homeostasis tuaj yeem txhawb nqa lub raum pob zeb hauv CKD miv. Raws li peb qhov kev tshawb pom, CKD txoj kev tshawb fawb hauv tib neeg tau pom tias cov ntshav tCa concentration yog ib qho kev ywj pheej ntawm nephrocalcinosis.11 Tsis tas li ntawd, kev koom tes ntawm tag nrho cov hypercalcemia thiab nephrocalcinosis tau pom nyob rau hauv tib neeg cov neeg mob tom qab hloov lub raum, 21 thiab cov neeg mob macroscopic nephrocalcinosis los ntawm CT imaging. muaj tCa thiab iCa ntau dua cov uas tsis muaj.22 Txawm li cas los xij, kev tshawb fawb histopathological hauv tib neeg pom tias tsis muaj kev sib koom ua ke ntawm cov ntshav tCa concentration nrog rau lub raum calcium cov ntsiab lus thiab lub raum tubular calcium deposition.12 Qhov tsis sib xws ntawm calcium kev koom tes hauv nephrocalcinosis ntawm cov kev tshawb fawb yog tshwm sim los ntawm txoj kev tshawb no. pej xeem heterogenicity, qauv loj, thiab raum calcification txoj kev nrhiav kom tau.
Kev noj haus ntawm PRD tau pom tias yog ib qho kev pheej hmoo ntawm nephrocalcinosis hauv CKD miv hauv peb txoj kev tshawb fawb. Kev txwv tsis pub noj phosphate cuam tshuam rau cov ntxhia thiab cov tshuaj hormones hauv CKD-MBD suav nrog kev txo qis hauv FGF23 thiab PTH.23,24 Ib txoj kev tshawb fawb tsis ntev los no tau pom tias qee cov miv CKD tau tsim ib qho kev nce ntxiv hauv tCa thiab iCa concentrations, nrog rau cov zis ntau dua calcium excretion, tom qab ib tug PRD pib.18 Kev noj zaub mov qis dua cov ntsiab lus phosphate thiab kev noj zaub mov ntau dua Ca:P piv, thaum piv nrog cov khoom lag luam uas tsim los rau cov neeg laus noj qab haus huv, 25 muaj peev xwm txhim kho plab hnyuv calcium nqus thiab nce plasma calcium concentration.26 Hauv tib neeg cov neeg mob, hypercalciuria yog ib qho tshwm sim. nephrocalcinosis risk factor.27 Nws yog postulated, yog li ntawd, hais tias nephrocalcinosis tej zaum yuav raug tsav los ntawm kev nce hauv plasma tCa concentration thiab txhim kho zis calcium excretion tom qab hloov mus rau PRD hauv CKD miv. Txawm li cas los xij, cov pov thawj ncaj qha los txhawb qhov kev xav no tsis tuaj yeem tau txais hauv peb txoj kev tshawb fawb thiab cov kev tshawb fawb yav tom ntej ntsuas cov zis electrolytes yog xav tau.
Peb cov txiaj ntsig tau pom tias nephrocalcinosis tsis zoo cuam tshuam nrog CKD kev loj hlob thiab tag nrho cov neeg tuag. Qhov kev tshawb pom no yog qhov xav tsis thoob vim tias nws yog qhov sib txawv ntawm qhov kev tshawb fawb yav dhau los hauv tib neeg uas tau pom tias muaj lub luag haujlwm tsis zoo ntawm nephrocalcinosis ntawm lub raum kev ua haujlwm los ntawm kev txheeb xyuas qhov sib raug zoo ntawm lub raum calcium cov ntsiab lus thiab cov ntshav creatinine concentration.12 Nephrocalcinosis txheeb xyuas los ntawm kev thaij duab (CT, ultrasonography, lossis radiography) kuj tau txuam nrog kev pheej hmoo ntawm cov kab mob raum kawg hauv tib neeg cov neeg mob.28 Kev tshawb fawb hauv CKD miv tau pom tias lub raum pob zeb hauv lub raum muaj kev sib koom ua ke nrog kev mob hnyav dua thiab mob fibrosis, qhia txog nws lub luag haujlwm hauv kev nrawm CKD.15 Txawm li cas los xij, tsis ntev los no. Cov kev tshawb fawb sib koom ua ke nrog tib neeg cov neeg mob raum CT duab pom tias tsis muaj kev sib koom ua ke ntawm lub raum ua haujlwm thiab lub raum calcification.22,29 Qhov kev soj ntsuam no zoo ib yam nrog peb cov txiaj ntsig thiab txhawb peb qhov kev xav tias nephrocalcinosis, rau qee yam, yuav tsis ua rau muaj kev cuam tshuam ncaj qha. ntawm lub raum ua haujlwm thiab pab txhawb rau CKD kev loj hlob. Txawm li cas los xij, cov kev tshawb fawb yav tom ntej yuav tsum tau ua kom nkag siab zoo dua nephrocalcinosis cuam tshuam rau CKD deterioration hauv miv.
Txawm hais tias kev noj PRD yog ib qho kev pheej hmoo ntawm tus mob nephrocalcinosis, peb qhov kev soj ntsuam kev ciaj sia tau pom tias kev txwv tsis pub noj phosphate (thaum ntau dua lossis sib npaug li 50 feem pua PRD tau noj) tau cuam tshuam nrog ntev MST thiab nce qhov txawv ntawm kev muaj sia nyob mus txog rau 3- quav rau CKD miv thaum piv rau cov miv uas noj lawv cov zaub mov noj (Table 4 thiab daim duab 4). Cov kev tshawb pom no txhawb nqa cov kev tshawb fawb yav dhau los uas pom tau tias muaj txiaj ntsig zoo los ntawm kev txwv kev noj zaub mov phosphate hauv CKD miv. Kev nce ntxiv hauv plasma creatinine, urea, thiab phosphate concentrations thiab kev txo qis hauv PCV thiab lub cev hnyav tshaj thawj xyoo tom qab kuaj mob CKD, ntxiv dag zog rau cov pov thawj tam sim no ntawm cov txiaj ntsig ntawm kev noj zaub mov phosphate txwv rau kev txo cov kab mob.23,24,32, 33 Hyperphosphatemia yog txuam nrog kev txo qis hauv lub raum ua haujlwm, 34 thiab phosphate binders tau pom tias tiv thaiv kev loj hlob ntawm CKD.35,36.
Plasma phosphate concentration thiab PCV yog qhov ua rau muaj kev ywj pheej ntawm txhua qhov kev tuag. Hyperphosphatemia thiab ntshav qab zib yog txuam nrog ntau dua CKD thiab cov tsos mob tsis zoo hauv miv thiab tib neeg. txwv tsis pub los ntawm kev hloov kho hormonal tswj cov txheej txheem, suav nrog nce FGF23 thiab PTH ntau lawm thiab txo cov calcitriol ntau lawm.6,43 Yog li ntawd, ntau dua plasma phosphate concentration ntawm CKD kev kuaj mob tuaj yeem qhia tau tias muaj kev cuam tshuam ntau dua phosphate homeostasis thiab cuam tshuam nrog kev pheej hmoo ntawm kev tuag. . Raws li peb cov txiaj ntsig, ib txoj kev tshawb fawb yav dhau los pom tias cov ntshav phosphate concentration siab dua nws tus kheej cuam tshuam nrog kev muaj sia nyob hauv 773 CKD cats.42 Cov kab mob ntshav qab zib hauv CKD yog ntau yam tab sis txo qis erythropoietin ntau lawm yog ib qho tseem ceeb pab txhawb.42,44 Hauv kev txhawb nqa peb. Kev tshawb pom, lwm cov kev tshawb fawb kuj pom muaj kev koom tes ntawm PCV qis thiab nce kev tuag hauv CKD miv, 38,39,45 tab sis tsis yog tag nrho.42 Interestingly, tsis muaj plasma creatinine concentration los yog IRIS staging yog ib tug kwv yees ntawm kev tuag nyob rau hauv txoj kev tshawb no, uas yog inconsistent. nrog rau yav dhau los cov kev tshawb fawb.38,39,42,45,46 Plasma creatinine concentration qhia txog GFR thiab yog ib tug surrogate biomarker feem ntau siv los ntsuas lub raum kev ua haujlwm.47 Qhov sib txawv tuaj yeem piav qhia los ntawm kev cais tawm ntawm IRIS theem 4 CKD miv hauv peb txoj kev tshawb fawb, thiab qhov piv txwv me me, tsuas yog 17 IRIS theem 3 CKD miv. Tsis tas li ntawd, 29 feem pua (n=15) ntawm cov miv nrog azotemic CKD hauv peb txoj kev tshawb fawb tsis tau txais kev tswj hwm kev noj haus rau CKD, uas tej zaum yuav cuam tshuam rau qhov tshwm sim thiab txwv tsis pub muaj qhov ntsuas qhov tseeb ntawm qhov kwv yees tus nqi ntawm plasma creatinine concentration, thiab muaj peev xwm. Lwm qhov hloov pauv thaum lub sijhawm kuaj CKD ntawm kev muaj sia nyob hauv peb txoj kev tshawb fawb.
Kev txheeb xyuas cov calcium deposition tau ua nrog ob txoj kev von Kossa siv nyiaj nitrate thiab Alizarin liab staining. Lub hauv paus ntsiab lus ntawm von Kossa yog ua raws li kev khi ntawm cov nyiaj ions nrog anions, xws li phosphate, oxalate, thiab carbonate, los ntawm cov ntaub so ntswg calcified thiab txo cov ntsev ntawm cov nyiaj ntsev, ua rau kev soj ntsuam ntawm cov xim dub xim nyiaj staining.20,48,49. Alizarin liab staining yog lwm cov txheej txheem siv rau kev ua qauv qhia ntawm calcium crystals.50 Nws khi ncaj qha rau calcium ions thiab tuaj yeem siv los sib txawv CaOx los ntawm CaP vim CaOx tsuas tuaj yeem stained nrog Alizarin Liab ntawm pH ntawm 7 tab sis tsis nyob ntawm pH 4.2, nrog rau yav tas los siv nyob rau hauv peb txoj kev tshawb no.51,52 Peb tau pom ib tug muaj zog correlation ntawm no 2 nephrocalcinosis staining txoj kev, tawm tswv yim hais tias cov mineral deposits feem ntau yog tsim los ntawm CaP. Qhov kev soj ntsuam no yog qhov nthuav vim tias feem ntau ntawm cov kab mob urinary uroliths hauv miv muaj CaOx.53 Nws yuav yog tias nag lossis daus ntawm CaP yog qhov yuav tsum tau ua ua ntej rau nephrocalcinosis, nephrolithiasis, lossis ob qho tib si hauv miv, txheej txheem uas zoo li tsim Randall cov quav hniav hauv tib neeg. 8 Micro-CT scanning tau ua nyob rau hauv FFPE raum cov qauv los txiav txim seb puas yog ib leeg von Kossa-stained swb yog tus sawv cev ntawm nephrocalcinosis. Peb pom muaj kev sib raug zoo nruab nrab ntawm micro- thiab macroscopic nephrocalcinosis, ntxiv kev txhawb nqa cov tswv yim thiab ntau txoj hauv kev siv rau kev faib cov nephrocalcinosis hnyav hauv peb txoj kev tshawb fawb, tab sis tawm tswv yim, raws li qhov xav tau, uas ib feem ntawm lub raum cov ntaub so ntswg muab kwv yees kwv yees ntawm qhov hnyav ntawm macroscopic nephrocalcinosis soj ntsuam los ntawm 3D duab.
Cistanche capsules
Peb qhov kev tshawb nrhiav rov qab muaj qee qhov kev txwv. Nephrocalcinosis tau txheeb xyuas los ntawm lub raum cov qauv sau ntawm necropsy, thiab nws tsis paub txog qhov twg lub raum calcification tsim nyob rau hauv cov miv no. Nephrocalcinosis tuaj yeem tsim ua ntej kuaj CKD. Tsuas yog miv nrog kev kuaj mob necropsy tau suav nrog hauv txoj kev tshawb no. Yog li ntawd, kev xaiv tsis ncaj ncees tuaj yeem tshwm sim txawm hais tias kev kuaj mob necropsy tau muab rau txhua tus neeg siv thaum lawv cov miv tau euthanized ntawm peb cov chaw kho mob. Muaj ntau hom kev noj zaub mov noj tau noj ua ntej hloov mus rau PRD. Txawm hais tias qhov tseeb cov ntxhia hauv cov zaub mov no nyuaj rau kev txiav txim siab, nws tau tshaj tawm tias qhov nruab nrab ntawm cov ntsiab lus phosphorus thiab Ca:P yog 3 g / Mcal thiab 1.3, raws li, ntawm 82 cov khoom noj miv muag.25 Yog li, nws yog qhov laj thawj. xav tias cov miv uas tau txais PRD tom qab kuaj mob CKD tau txais kev noj zaub mov tsawg dua phosphate thiab noj zaub mov ntau dua Ca:P dua li cov uas txuas ntxiv noj zaub mov noj. Vim tias qhov kev faib tawm ntawm pawg PRD tsis yog randomized (txhua tus miv tau muab PRD ua ib feem ntawm lawv cov tswv yim tswj hwm rau CKD hauv peb txoj kev tshawb fawb vim li cas kev coj ncaj ncees), kev xaiv tsis ncaj ncees yuav raug qhia, txawm hais tias tsis muaj qhov sib txawv ntawm cov kev hloov pauv hauv clinicopathological tau txheeb xyuas ntawm 3 pawg nyob rau hauv lub hauv paus. Yog li ntawd, PRD cov teebmeem ntawm CKD kev nce qib thiab kev tuag yuav tsum tau txhais nrog ceev faj vim tias qhov tsis paub tias yog vim li cas cov miv tsis noj PRD tuaj yeem cuam tshuam rau lawv txoj sia nyob tsis zoo. Tsis tas li ntawd, ntau yam PRDs, nrog rau qhov sib txawv ntawm cov ntsiab lus phosphorus thiab Ca:P, tau muab thoob plaws lub sijhawm kawm thiab nws tsis tuaj yeem suav tias cov txiaj ntsig los ntawm peb txoj kev tshawb fawb tuaj yeem ua rau tag nrho cov khoom lag luam PRD vim tias txawm hais tias cov khoom siv dav dav ntawm lub raum tshuaj. kev noj zaub mov zoo sib xws, kev hloov pauv hauv kev noj zaub mov muaj nyob. Ib txoj kev tshawb nrhiav ntev ntev yuav tsum tau tshawb xyuas ntxiv txog qhov ua rau muaj txiaj ntsig ntawm kev noj zaub mov phosphate txwv rau nephrocalcinosis. Intriguingly, qhov luaj li cas ntawm macroscopic calcification yuav raug soj ntsuam siv micro-CT scan nyob rau hauv peb txoj kev tshawb no. Txawm li cas los xij, qhov ntim ntawm FFPE raum cov ntaub so ntswg tuaj yeem raug overestimated vim muaj kev cuam tshuam ntawm paraffin wax. Txawm hais tias kev ntsuas ntawm ntau qhov chaw ntawm cov ntaub so ntswg ntawm qhov tob ib ntus tau txais los muab kev kwv yees zoo tshaj plaws ntawm cov ntaub so ntswg ntim, VN: KT piv uas muaj feem cuam tshuam tau qis dua. Txawm li cas los xij, qhov muaj peev xwm no suav tias muaj qhov cuam tshuam me me rau kev sib raug zoo ntawm micro- thiab macroscopic nephrocalcinosis qhia. Thaum kawg, nephrocalcinosis tau cuam tshuam nrog hyperparathyroidism hauv tib neeg cov neeg mob.29 Qhov kev koom tes no feem ntau yog tshwm sim los ntawm cov ntshav plasma thiab zis ntau ntxiv ntawm calcium, tso zis tawm ntawm phosphate, thiab lub raum reabsorption ntawm calcium stimulated los ntawm PTH, ua rau lub raum calcification.54, 55 Fibroblast kev loj hlob yam tseem ceeb-23 kuj tau hais kom koom nrog hauv nephrocalcinosis.56 Hmoov tsis zoo, cov ntaub ntawv ntawm FGF23, PTH, thiab cov zis electrolytes tsis muaj nyob hauv peb txoj kev tshawb fawb; Yog li, lawv txoj kev koom tes hauv nephrocalcinosis tsis tuaj yeem tshawb xyuas. Qhov kev txwv no txwv tsis pub muaj kev soj ntsuam ntxiv ntawm qhov muaj peev xwm pab tau ntawm hypercalciuria lossis hyperphosphaturia rau nephrocalcinosis. Calcium xwm txheej hauv cov miv hauv peb txoj kev tshawb fawb tau soj ntsuam los ntawm tCa vim tias qhov kev ntsuas iCa tsis muaj nyob hauv cov miv feem ntau. Cov kev tshawb fawb ntxiv, suav nrog ntshav plasma FGF23, PTH, iCa, thiab ntsuas cov zis calcium thiab phosphate, tau lees paub tias cov yam ntxwv no ua lub luag haujlwm tseem ceeb hauv nephrocalcinosis.
Sib sau ua ke, peb tau pom tias ntau dua plasma tCa concentration ntawm CKD kev kuaj mob thiab kev txwv kev noj zaub mov phosphate yog qhov muaj feem pheej hmoo rau nephrocalcinosis txawm hais tias causality tsis tuaj yeem txiav txim siab. Extraosseous calcification yog txheej txheem ntau yam thiab nyuaj uas tau tswj hwm los ntawm ntau yam inducers thiab inhibitors.57,58 Lub luag haujlwm ntawm endogenous calcification inhibitors, xws li magnesium, fetuin-A, thiab pyrophosphate, ntawm nephrocalcinosis tseem yuav tau tshawb xyuas hauv CKD miv. Tsis tas li ntawd, nyob rau hauv miv, nephrocalcinosis tsis tshwm sim los cuam tshuam nrog kev loj hlob sai ntawm cov kab mob thiab kev pheej hmoo ntawm txhua qhov kev tuag hauv peb txoj kev tshawb fawb. Txawm li cas los xij, kev noj ntau dua lossis sib npaug li 50 feem pua PRD tuaj yeem txo qhov kev pheej hmoo ntawm txhua qhov kev tuag thiab kev muaj sia nyob ntev hauv CKD miv. Cov kev soj ntsuam tsis sib xws no yuav tsum tau kawm ntxiv. Hauv miv, CKD yog ib qho mob heterogeneous uas muaj qhov sib txawv ntawm kev nce qib uas feem ntau yuav tau tsav los ntawm ntau yam. Peb cov txiaj ntsig cuam tshuam cuam tshuam txog kev cuam tshuam hauv phosphate homeostasis hauv kev txhawb nqa kev loj hlob sai ntawm CKD txawm tias nephrocalcinosis tsis tshwm sim hauv cov miv no. Cov kev tshawb fawb yav tom ntej uas ntsuas kev txhim kho thiab kev loj hlob ntawm nephrocalcinosis hauv miv nrog azotemic CKD tau lees paub thiab tuaj yeem ua rau lub hauv paus tshiab rau kev kuaj mob thiab kev kho mob hauv kev tswj hwm CKD-MBD hauv miv.
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Pak-Kan Tang1|Rosanne E. Jepson2|Yu-Mei Chang3|Rebecca F. Geddes2|Mark Hopkinson1|Jonathan Elliott 1
1 Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, United Kingdom
2 Department of Clinical Science and Services, Royal Veterinary College, University of London, London, United Kingdom
3 Kev Tshawb Fawb Kev Pabcuam, Royal Veterinary College, University of London, London, United Kingdom
