Ntsev, Tab sis tsis noj cov protein, yog txuam nrog cov kab mob nrawm nrawm hauv Autosomal Dominant Polycystic raum Kab Mob

Hu rau: emily.li@wecistanche.com

Bart J. Kramers1 , Iris W. Koorevaar1 , Joost PH Drenth2 , Johan W. de Fijter3 , Antonio Gomes Neto1 , Dorien JM Peters4 , Priya Vart5 , Jack F. Wetzels5 , Robert Zietse6 , Ron T. Gansevoort1 thiab Esther

1 Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Lub Netherlands; 2 Department of Gastroenterology thiab Hepatology, Radboud University Medical Center, Nijmegen, Netherlands; 3 Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands; 4 Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; 5 Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands; thiab 6 Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands

KEYWORDS:ADPKD; ntsev; vasopressin; urea

Copyright ª 2020, International Society of Nephrology. Tshaj tawm los ntawm Elsevier Inc. Qhov no yog ib tsab xov xwm qhib-access nyob rau hauv daim ntawv tso cai CC BY.

Cov ntawv xov xwm: Esther Meijer, Kws Tshaj Lij Chaw rau PolycysticLub raumKab mob, Division of Nephrology, University Medical Center Groningen, PO 30.001,9700 RB Groningen, lub Netherlands. E-mail: B.J.Kramers@umcg.nl Tau txais 14 Lub Ob Hlis 2020; hloov kho 10 Plaub Hlis 2020; tau txais 30 Plaub Hlis 2020; Tshaj tawm online 10 Lub Rau Hli 2020 Hauv autosomal dominant polycysticraumkab mob(ADPKD), tsuas muaj cov ntaub ntawv tsis tshua muaj tshwm sim ntawm cov ntsev thiab cov protein kom tsawg ntawm cov kab mob. Ntawm no peb tau kawm txog kev koom tes ntawm cov khoom noj khoom haus no nrog tus nqi ntawm cov kab mob kev loj hlob hauv ADPKD thiab dab tsi yog qhov kev kho kom haum xeeb yog los ntawm kev txheeb xyuas qhov kev soj ntsuam ntawm 589 tus neeg mob nrog ADPKD. Kev noj ntsev thiab cov protein tau kwv yees los ntawm 24- teev cov zis kuaj thiab cov ntshav copeptin concentration tau ntsuas raws li tus neeg sawv cev rau vasopressin. Lub koom haum ntawm kev noj haus nrog kev hloov pauv txhua xyoo hauv kev kwv yees glomerular filtration rate (eGFR) thiab qhov siab-hloov tag nrho lub raum ntim (htTKV) kev loj hlob tau txheeb xyuas nrog cov qauv sib xyaw. Nyob rau hauv cov ntaub ntawv ntawm cov koom haum tseem ceeb, kev kho kom haum xeeb tshuaj ntsuam xyuas tau ua los qhia txog cov txheej txheem muaj peev xwm. Cov neeg mob no (59 feem pua ​​​​poj niam) muaj lub hnub nyoog nruab nrab ntawm 47, eGFR 64 mL / min / 1.73m2 thiab qhov nruab nrab htTKV yog 880 mL. Qhov nruab nrab kwv yees kev noj ntsev yog 9.1 g / hnub thiab protein ntau 84 g / hnub. Thaum lub sij hawm nruab nrab ntawm 4. 0 xyoo, eGFR tau ntsuas qhov nruab nrab ntawm rau lub sij hawm, thiab 24- teev cov zis tau sau qhov nruab nrab ntawm tsib zaug. Kev noj ntsev tau cuam tshuam nrog kev hloov pauv txhua xyoo hauv eGFR ntawm L{{20}}.11 (95 feem pua ​​​​ntawm kev ntseeg siab 0.20 - L0. 02] mL / min / 1.73m2) ib gram ntawm ntsev, whereas protein tsis tau (L0.00001 [L0.01 - 0.01] mL / min / 1.73m2) ib gram ntawm

protein). Cov txiaj ntsig ntawm kev noj ntsev ntawm eGFR txoj kab nqes yog qhov cuam tshuam loj heev los ntawm cov ntshav copeptin (kev tshuaj xyuas tsis zoo: 77 feem pua ​​​​kev kho mob, thiab, kev tshuaj xyuas kho: 45 feem pua ​​​​kev kho mob), tab sis tsis yog los ntawm cov ntshav siab systolic. Yog li, ntsev ntau dua, tab sis tsis noj cov protein ntau yuav ua rau ADPKD tsis zoo. Qhov kev sib haum xeeb loj heev los ntawm plasma copeptin qhia tau hais tias qhov kev cuam tshuam no feem ntau yog qhov tshwm sim los ntawm kev nce ntsev hauv vasopressin.

Nyob rau hauv mobraumkab mob(CKD), kev txwv ntsev yog tawm tswv yim kom qeeb tus kab mob.1 txwv ntsev txo cov ntshav siab thiab potentiates renoprotective teebmeem ntawm renin-angiotensin-aldosterone system (RAAS) blockade.2 Lub luag hauj lwm ntawm kev noj cov protein txwv hauv kev ua kom qeeb ntawm CKD yog ntau dua. controversial, txawm hais tias ntau qhov kev ntsuam xyuas meta qhia tau hais tias muaj txiaj ntsig, txawm tias muaj txiaj ntsig me me.3,4 Hauv autosomal dominant polycysticraum kab mob(ADPKD) tshwj xeeb, tsuas muaj cov ntaub ntawv tsis txaus ntawm lub raum cuam tshuam ntawm ntsev thiab protein kom tsawg.

Hauv Consortium rau Radiologic Imaging Studies hauv PolycysticLub raum Kab mob(CRISP) pawg, kev soj ntsuam kev tshawb fawb hauv 241 cov neeg mob ADPKD nrog cov kab mob thaum ntxov, kev tso zis ntau dua sodium ntau dua (qhia tias muaj ntsev ntau dua) tau cuam tshuam nrog kev loj hlob ntawm lub raum sai. Hauv kev soj ntsuam tom qab hoc ntawm HALT Progression ntawm PolycysticLub raumKab mob(HALT-PKD) txoj kev tshawb fawb, kev sim tshuaj ntsuam xyuas randomized hauv 1044 cov neeg mob nrog rau theem tom qab ADPKD, sodium excretion tau cuam tshuam nrog qhov qis tshaj qhov kwv yees glomerular filtration rate (eGFR) poob rau cov neeg mob tom qab-theem ADPKD tab sis tsis yog rau cov neeg mob thaum ntxov. ADPKD.5,6 Nws tau raug qhia tias kev koom tes nrog eGFR poob qis tuaj yeem tshwm sim los ntawm kev txwv ntsev muaj peev xwm ua rau lub raum tiv thaiv cov teebmeem ntawm RAAS blockade, zoo ib yam li nonADPKD CKD.6 Lwm qhov kev piav qhia tuaj yeem yog tias kev noj ntsev ua rau cov kab mob nrawm nrawm hauv ADPKD los ntawm stimulation ntawm vasopressin secretion. Vasopressin paub tias muaj feem cuam tshuam txog kev kis kab mob hauv ADPKD.7-9 Ib qho tseem ceeb ntawm vasopressin secretion yog plasma sodium concentration, 10 uas nce tom qab noj ntsev.

Cistanche yog qhov zoo rau lub raum

Raws li urinary urea excretion tsis tau ntsuas nyob rau hauv HALT-PKD mus sib hais, nws tsis paub meej tias cov protein kom tsawg kuj tseem cuam tshuam nrog eGFR poob.6 Cov txiaj ntsig ntawm kev noj cov protein tsawg ntawm tus nqi ntawm eGFR poob tau raug kawm hauv kev soj ntsuam tom qab hoc ntawm Kev Hloov Kho Kev Noj Qab Haus Huv Hauv Lub Raum Kab Mob (MDRD) txoj kev tshawb fawb, uas cov zaub mov tsis muaj protein ntau tau muab piv rau kev noj zaub mov ib txwm muaj (kev kawm A) thiab kev noj zaub mov tsis muaj protein ntau tau muab piv rau cov khoom noj muaj protein tsawg (kawm B). Hauv pab pawg ntawm 200 tus neeg mob nrog ADPKD, tsis muaj qhov sib txawv tseem ceeb hauv ob qho kev kawm; Txawm li cas los xij, cov txiaj ntsig tau suav tias tsis muaj tseeb los ntawm cov neeg tshawb xyuas, thiab lwm yam vim tsis muaj hwj chim.11,12

Muab cov ntaub ntawv tsis tshua muaj thiab tsis lees paub, peb tsom los tshawb xyuas qhov sib txheeb ntawm cov ntsev thiab cov protein kom tsawg thiab lub raum ua haujlwm poob qis hauv ADPKD. Txhawm rau hais txog lub hom phiaj no, peb tau txheeb xyuas cov ntaub ntawv ntawm cov neeg mob nrog ADPKD hauv pawg soj ntsuam loj. Peb kuj tseem tsom mus kawm seb lub koom haum muaj peev xwm tau kho los ntawm vasopressin lossis los ntawm lwm yam kev muaj peev xwm.

Daim duab 1 |Txhim kho Kev Tshaj Tawm Txog Kev Tshawb Fawb Kev Tshawb Fawb Hauv Kev Kab Mob Kab Mob (STROBE) cov duab kos. DIPAK, Tsim Cov Kev Pabcuam kom Tsis Muaj Kev Loj Hlob ntawm Autosomal Dominant PolycysticLub raumKab mob; eGFR, kwv yees glomerular

lim tus nqi; FU, ua raws.

TSEEM CEEB

Cov kev khiav dej num tau piav qhia hauv daim duab 1. Cov yam ntxwv ntawm lub hauv paus tau qhia hauv Table 1. Qhov nruab nrab hnub nyoog yog 47 ntxiv rau - 11 xyoo, 59 feem pua ​​​​ntawm cov neeg koom yog poj niam, eGFR yog 64 ntxiv rau -24 ml/min ib 1.73 m2 thiab nruab nrab qhov siab-kho tag nrho lub raum ntim (htTKV) yog 880 ml (interquartile range [IQR]: 549, 1352). Tsis muaj qhov sib txawv tseem ceeb ntawm hnub nyoog, poj niam txiv neej, eGFR, thiab htTKV hauv 205 tus neeg mob uas raug cais tawm vim tsis muaj cov ntaub ntawv rov qab los. Sodium excretion yog 156 ntxiv rau - 65 mmol / 24 teev ntawm lub hauv paus, sib xws nrog kwv yees kev noj ntsev ntawm 9.1 ntxiv rau - 3.8 g. Urea excretion yog 390 ntxiv rau - 132 mmol / 24 teev, sib xws nrog kwv yees cov protein ntau ntawm 84 ntxiv rau - 25 g. Sodium excretions thiab urea excretion thaum lub sij hawm tag nrho cov mus ntsib nyob rau hauv lub tsim kev cuam tshuam rau Halt Progression ntawm Autosomal Dominant PolycysticLub raumKab mob(DIPAK) 1 mus sib hais thiab DIPAK soj ntsuam cohort muaj nyob rau hauv daim duab 2.

Thaum lub sijhawm ua raws li nruab nrab ntawm 4.0 xyoo (IQR: 2.6, 5.0), eGFR raug soj ntsuam 6 zaug (IQR: 5, 14) thiab 24- teev tso zis tau sau 5 zaug (IQR: 4, 7). Qhov nruab nrab txhua xyoo hloov pauv hauv eGFR yog 3.50 ml / min ntawm 1.73 m2 toj xyoo (95 feem pua ​​​​ntawm kev ntseeg siab [CI]: 3.70 txog 3.29).

Sodium excretion thiab urea excretion

Sodium excretion tau sib raug zoo nrog urea excretion (tus qauv b ¼ {{{{{{0}}}.61, unstandardized b ¼ 1.8 mmol urea ib mmol sodium; 95 feem pua ​​​​CI: 1.6 rau 2.0; P < 0="" 0{{5{6{62}}}}}}1).="" hauv="" kev="" tshuaj="" xyuas="" cov="" qauv="" sib="" xyaw,="" sodium="" excretion="" tsis="" muaj="" feem="" cuam="" tshuam="" nrog="" kev="" hloov="" pauv="" hauv="" egfr="" (-="" 0.16="" ml="" min="" ib="" 1.73="" m2="" ib="" xyoos="" twg="" rau="" 18="" mmol="" ntawm="" sodium;="" 95="" feem="" pua="" ​​​​ci:="" -0.24="" rau="" {{="" 20}}.08;="" p="">< 0.001),="" raws="" li="" yog="" urea="" excretion="" (-="" 0.03="" ml="" min="" ib="" 1.73="" m2="" ib="" xyoos="" twg="" rau="" 40="" mmol="" ntawm="" urea;="" 95="" feem="" pua="" ​​​​ci:="" -="" 0.05="" rau="" {="" {33}}.001;="" p="" ¼="" 0.04).="" hauv="" kev="" txheeb="" xyuas="" ntau="" yam="" sib="" txawv,="" hloov="" kho="" rau="" hnub="" nyoog,="" poj="" niam="" txiv="" neej,="" thaj="" tsam="" ntawm="" lub="" cev="" (bsa),="" lub="" hauv="" paus="" httkv,="" thiab="" dna="" hloov="" pauv,="" kev="" koom="" tes="" ntawm="" sodium="" excretion="" nrog="" kev="" hloov="" hauv="" egfr="" tseem="" tseem="" ceeb="" (table="" 2).="" hauv="" qhov="" sib="" piv,="" kev="" koom="" tes="" ntawm="" urea="" excretion="" thiab="" egfr="" txoj="" kab="" nqes="" poob="" qhov="" tseem="" ceeb="" tom="" qab="" kev="" hloov="" kho="" rau="" cov="" neeg="" muaj="" peev="" xwm="" confounders="" (table="" 2).="" daim="" duab="" 3="" qhia="" txog="" kev="" sib="" raug="" zoo="" ntawm="" sodium="" excretion="" thiab="" urea="" excretion="" thiab="" egfr="" nqes="" hav.="" raws="" li="" kev="" tso="" tawm="" ntawm="" sodium="" thiab="" urea,="" peb="" kwv="" yees="" cov="" ntsev="" thiab="" cov="" protein="" kom="" tsawg.="" hauv="" cov="" qauv="" sib="" txawv,="" kev="" sib="" koom="" ua="" ke="" ntawm="" ntsev="" kom="" tsawg="" nrog="" kev="" hloov="" hauv="" egfr="" yog="" -="" 0.11="" ml="" min="" ib="" 1.73="" m2="" ib="" xyoos="" ib="" gram="" ntsev="" (95="" feem="" pua="" ​​​​ci:="" -="" 0.20="" rau="" {{48="" }}.02;="" p="" ¼="" 0.02),="" kev="" sib="" koom="" ua="" ke="" ntawm="" cov="" protein="" kom="" tsawg="" nrog="" kev="" hloov="" hauv="" egfr="" tsis="" tseem="" ceeb="" (-="" 0.00001="" ml="" min="" ib="" 1.73="" m2="" ib="" xyoos="" ib="" gram="" protein;="" 95%="" ci:="" {{58}="" }.01="" txog="" 0.01;="" p="" ¼="" 0.9)="" (table="" ntxiv="" s1a).="" thaum="" peb="" tsis="" suav="" cov="" neeg="" mob="" uas="" siv="" lanreotide="" thaum="" lub="" sijhawm="" sim="" dipak-1,="" cov="" txiaj="" ntsig="" tau="" zoo="" ib="" yam="" (table="" ntxiv="">

Hauv kev txheeb xyuas qhov tsis sib xws, ob qho tib si sodium excretion thiab urea excretion tau txuam nrog htTKV kev loj hlob ({{0}}.63 feem pua ​​​​ntawm ib xyoos ib 18 mmol sodium; 95 feem pua ​​​​CI: 0.4{{8} } rau {{10}}.87; P < 0.="" 0,001="" ib.).="" kev="" koom="" tes="" ntawm="" sodium="" excretion="" nrog="" httkv="" kev="" loj="" hlob="" tseem="" ceeb="" heev="" tom="" qab="" kev="" hloov="" kho="" rau="" hnub="" nyoog,="" poj="" niam="" txiv="" neej,="" bsa,="" lub="" hauv="" paus="" ntawm="" httkv,="" thiab="" dna="" hloov="" pauv,="" thaum="" lub="" koom="" haum="" ntawm="" urea="" excretion="" poob="" qhov="" tseem="" ceeb="" (table="">

Table 1| Cov yam ntxwv ntawm lub hauv paus

Daim duab 2| Txhais tau tias sodium excretion thiab urea excretion thaum mus ntsib txhua xyoo, nrog kwv yees ntsev thiab protein kom tsawg. Whiskers qhia txog 5 feem pua ​​​​rau 95 feem pua. BL, pib.

Rooj 2| Kev koom tes ntawm sodium thiab urea excretion nrog eGFR nqes hav (n [553)

BSA, thaj tsam ntawm lub cev; CI, kev ntseeg siab luv; eGFR, kwv yees glomerular pom tus nqi; Kev kwv yees, kev kwv yees; htTKV, qhov siab-hloov tag nrho lub raum ntim; PKD, polycysticraumkab mob; ref, siv. Kev kwv yees thiab P qhov tseem ceeb tau qhia rau kev sib cuam tshuam ntawm kev hloov pauv nrog lub sijhawm. Kev sib cuam tshuam nrog lub sijhawm qhia txog qhov cuam tshuam ntawm qhov sib txawv ntawm eGFR lub sijhawm: uas yog, qhov cuam tshuam ntawm eGFR nqes hav. Qauv 1 qhia txog kev sib koom ua ke ntawm sodium excretion nrog eGFR nqes hav. Qauv 2 qhia txog kev sib koom ua ke ntawm urea excretion nrog eGFR nqes hav. Qauv 3 qhia txog kev sib koom ua ke ntawm sodium thiab urea excretion nrog eGFR nqes hav hauv tib tus qauv. Txhua tus qauv tau hloov kho rau lub sijhawm, hnub nyoog, poj niam txiv neej, BSA, thiab lawv cov kev cuam tshuam nrog lub sijhawm. Qhov kev kwv yees rau qhov sib txawv tsis cuam tshuam nrog lub sijhawm (tsis pom) qhia txog qhov tshwm sim ntawm qhov sib txawv ntawm qhov pib ntawm eGFR (kev cuam tshuam).

Kev soj ntsuam rhiab heev

As sensitivity analyses, we repeated the linear mixed model analyses with salt and protein intake per kilogram ideal body weight, and salt and protein per kilogram actual body weight (Supplementary Table S1C and D). As additional sensitivity analyses, we repeated the analyses using baseline 24-hour excretions instead of mean excretions, we subsequently used median excretions instead of mean excretions. We excluded 24-hour urine collections if the 24-hour creatinine excretion was >30 feem pua ​​​​ntawm cov neeg koom nrog qhov nruab nrab creatinine excretion. Thaum kawg, peb tau ua qhov kev soj ntsuam rhiab heev uas peb hloov kho rau albuminuria. Tag nrho cov kev ntsuam xyuas no tau txais txiaj ntsig zoo ib yam.

Kev tshuaj xyuas pab pawg

Peb tau kuaj xyuas qhov sib txawv ntawm kev sib koom ntawm kev noj ntsev thiab kev hloov pauv txhua xyoo hauv eGFR thoob plaws ntau pawg (Daim duab 4). Kev noj ntsev ntau dua tau cuam tshuam nrog eGFR poob sai dua lossis nruab nrab eGFR hauv txhua pab pawg. Lub sij hawm sib cuam tshuam ntawm kev siv RAAS thaiv thiab kev noj ntsev yog qhov tseem ceeb (P ¼ 0 02), nrog rau kev sib raug zoo tsis zoo rau cov neeg mob uas tsis siv RAAS thaiv. Muaj ib qho kev hloov mus rau qhov tseem ceeb ntawm kev sib cuam tshuam nrog lub hnub nyoog (P ¼ 0.06) thiab lub hauv paus eGFR (P ¼ 0.07). Piv nrog rau cov neeg mob uas tsis siv RAAS blockade, RAAS blockade cov neeg siv muaj cov ntsev zoo sib xws, tab sis lawv laus dua, feem ntau yog poj niam, muaj eGFR qis dua, thiab muaj lwm qhov sib txawv hauv qab (Table Ntxiv S2). Muaj kev noj ntsev ntau dua qhov nruab nrab hauv cov neeg mob hluas dua li cov neeg laus (9.0 - 2.7 g vs. 8.3 - 2.5 g; P ¼ 0.002). Kev noj ntsev zoo sib xws hauv cov neeg mob uas muaj eGFR siab dua (8.8 2.8 g) thiab cov neeg mob qis dua eGFR (8.4 2.5 g; P ¼ 0.07).

Kev sib kho los ntawm ntshav siab, RAAS, lossis copeptin

Peb tau ua cov qauv kev sib npaug sib npaug los ntsuas rau cov neeg tuaj yeem kho kom haum xeeb ntawm lub koom haum ntawm kev tso tawm thiab eGFR txoj kab nqes. Ua ntej, peb tau sim seb cov nyhuv puas yog kho los ntawm kev cuam tshuam ntawm cov ntshav siab. Nyob rau hauv cov qauv no, tag nrho cov nyhuv ntawm kwv yees

ntsev kom tsawg ntawm eGFR nqes hav tau kwv yees li {{{{10}}}}}.13 ml/min ib 1.73 m2 ib xyoos ib gram ntawm cov ntsev ntsev (95 feem pua ​​​​CI: -0.23 rau - 0.02; P ¼ 0.03). Qhov cuam tshuam ncaj qha ntawm ntshav siab ntawm eGFR nqes hav yog qhov tseem ceeb (0.02 ml / min ib 1.73 m 2 ib xyoos ib zaug.

hli Hg; 95% CI: - 0.03 rau -0.01; P 0.02). Txawm li cas los xij, qhov cuam tshuam ncaj qha ntawm kev noj ntsev ntawm cov ntshav siab systolic yog qhov tsis tseem ceeb (P ¼ 0.3). Yog li, qhov cuam tshuam ncaj qha los ntawm systolic ntshav siab tsis tseem ceeb (kwv yees: - 0.005; 95 feem pua ​​​​CI:

{0}}01 txog 0.003; P ¼ 0.3). Txawm li cas los xij, tsis muaj kev sib haum xeeb tseem ceeb los ntawm systolic ntshav siab.

Table 3| Lub koom haum ntawm kwv yees kev noj ntsev thiab noj cov protein ntau nrog kev loj hlob htTKV txhua xyoo (n [283)

Peb tau soj ntsuam seb cov txiaj ntsig ntawm kev noj ntsev ntawm eGFR puas yog kho los ntawm plasma renin thiab plasma aldosterone hauv cov neeg mob uas tsis siv RAAS blockade (n ¼ 58). Hauv cov neeg mob no, qhov nruab nrab plasma renin yog 1{{10}}}.6 pg/ml (IQR: 6.5, 16.7) thiab nruab nrab plasma aldosterone yog 265 pg/ml (IQR: 181, 363). Ob qho kev cuam tshuam ncaj qha tsis yog qhov tseem ceeb (P ¼ 0.3 thiab 0.4, raws li), qhia tau hais tias tsis muaj kev sib haum xeeb tseem ceeb los ntawm plasma renin lossis ntshav aldosterone.

Tom ntej no, peb tau tshawb xyuas seb lub koom haum ntawm sodium excretion thiab eGFR nqes hav yog kho los ntawm copeptin (qhov nruab nrab ntawm 2 qhov tseem ceeb). Muaj kev sib raug zoo ntawm 2 plasma copeptin kev ntsuas (Spearman coefficient: 0.85; P < 0="" 001)="" (cov="" duab="" ntxiv="" s1).="" nyob="" rau="" hauv="" tus="" qauv="" crude,="" tag="" nrho="" cov="" nyhuv="" ntawm="" ntsev="" kom="" tsawg="" ntawm="" egfr="" nqes="" hav="" yog="" kwv="" yees="" li="" -="" 0.16="" (95="" feem="" pua="" ​​ci:="" -0.23="" rau="" -="" 0.09)="" ml/min="" ib="" 1.73="" m2="" ib="" xyoos="" ib="" gram="" ntawm="" cov="" ntsev="" ntsev="" (p=""><0.001). cov="" txiaj="" ntsig="" tsis="" ncaj,="" sib="" kho="" los="" ntawm="" copeptin,="" tau="" kwv="" yees="" tias="" yog="" -="" 0.12="" (95="" feem="" pua="" ​​​​ci:="" -0.18="" rau="" -="" 0.08)="" ml/min="" ib="" 1.73="" m2="" ib="" xyoos="" ib="" gram="" ntawm="" lub="" rooj="" ntsev="" (p=""><0.001). yog="" li,="" cov="" txiaj="" ntsig="" ntawm="" kev="" noj="" ntsev="" ntawm="" egfr="" nqes="" hav="" yog="" kho="" los="" ntawm="" copeptin="" los="" ntawm="" 77="" feem="" pua="" ​​(95="" feem="" pua="" ​​​​ci:="" 32="" feem="" pua="" ​​​​rau="" 100="" feem="">

Tom qab qhov kev ntsuam xyuas tsis zoo no, cov qauv kev sib kho nrog copeptin tau hloov kho rau cov neeg muaj peev xwm confounders. Hauv kev txheeb xyuas ntau yam sib txawv, lub hnub nyoog hauv paus, poj niam txiv neej, thiab eGFR tau cuam tshuam nrog ntshav copeptin nyob rau sab saum toj ntawm kev kwv yees kev noj ntsev. Kev sib deev thiab DNA kev hloov pauv tau cuam tshuam nrog eGFR txoj kab nqes saum toj ntawm kev noj ntsev lossis ntshav ntshav copeptin. Tom qab hloov kho rau cov kev hloov pauv no, tag nrho cov txiaj ntsig ntawm kev noj ntsev ntawm eGFR txoj kab nqes yog {{{{10}}}}.14 (95 feem pua ​​​​CI: -0.23 rau -0 . .02; P ¼ 0.004) (Daim duab 5). Yog li, hauv kev tshuaj ntsuam xyuas, cov txiaj ntsig ntawm kev noj ntsev ntawm eGFR nqes hav yog kho los ntawm copeptin los ntawm 45 feem pua ​​(95 feem pua ​​​​CI: 1 feem pua ​​​​rau 89 feem pua). Tsis muaj qhov qhia tau tias muaj kev cuam tshuam ntawm kev ntsuas qhov tsis txaus ntseeg ntawm cov txiaj ntsig no (Table Ntxiv S3).

Peb rov ua qhov kev sib kho kom haum xeeb nrog htTKV txoj kab nqes raws li qhov sib txawv ntawm qhov sib txawv. Tag nrho cov txiaj ntsig ntawm kev noj ntsev ntawm htTKV txoj kab nqes yog {{0}}}.59 feem pua ​​​​htTKV kev loj hlob ib xyoo ib gram cov lus ntsev (95 feem pua ​​​​CI: 0.33 rau 0. {6}}; P < 0="" 001).="" tsis="" muaj="" kev="" sib="" haum="" xeeb="" tseem="" ceeb="" los="" ntawm="" systolic="" ntshav="" siab="" (p="" ¼="" 0.5).="" cov="" nyhuv="" tsis="" ncaj="" ncees,="" kho="" los="" ntawm="" plasma="" copeptin,="" yog="" qhov="" tseem="" ceeb="" (0.15%="" httkv="" kev="" loj="" hlob="" ib="" xyoos="" ib="" gram="" ntawm="" cov="" ntsev="" ntsev;="" 95="" feem="" pua="" ​​​​ci:="" 0.04="" txog="" 0.25;="" p="" ¼="" 0.006).="" yog="" li,="" cov="" txiaj="" ntsig="" ntawm="" kev="" noj="" ntsev="" ntawm="" httkv="" txoj="" kab="" nqes="" yog="" kho="" los="" ntawm="" plasma="" copeptin="" los="" ntawm="" 25="" feem="" pua="" ​​(95="" feem="" pua="" ​​​​ci:="" 4="" feem="" pua="" ​​​​rau="" 45="" feem="">

Peb tau ua qhov kev tshawb nrhiav kev sib kho kom haum xeeb los ntsuas seb qhov cuam tshuam ntawm copeptin ntawm eGFR txoj kab nqes puas tau hloov kho los ntawm htTKV kev loj hlob. Tus nqi ntawm htTKV hloov pauv tau cuam tshuam nrog tus nqi ntawm eGFR hloov pauv {{0}}.38 feem pua ​​​​ntawm ib ml / min rau 1.73 m 2 (P < 0="" 00="" }1).="" hauv="" kev="" tshuaj="" xyuas="" tsis="" zoo,="" tag="" nrho="" cov="" txiaj="" ntsig="" ntawm="" lub="" cev="" hloov="" pauv="" plasma="" copeptin="" ntawm="" egfr="" nqes="" hav="" yog="" 1.51="" (95="" feem="" pua="" ​​​​ci:="" 1.88="" rau="" 1.14;="" p="">< 0.001),="" qhov="" cuam="" tshuam="" ncaj="" qha="" los="" ntawm="" httkv="" kev="" loj="" hlob="" yog="" 0.20="" (95="" feem="" pua="" ​​​​ci:="" 0.34="" txog="" 0.05;="" p="" ¼="" 0.008),="" ergo="" 13="" feem="" pua="" ​​(95="" feem="" pua="" ​​ci:="" 3="" feem="" pua="" 23="" feem="" pua)="" kev="" sib="" kho.="" txawm="" li="" cas="" los="" xij,="" tom="" qab="" kev="" hloov="" kho="" rau="" cov="" neeg="" tsis="" sib="" haum="" xeeb,="" qhov="" kev="" kho="" kom="" haum="" xeeb="" no="" tau="" poob="" qhov="" tseem="" ceeb="" nrog="" kev="" cuam="" tshuam="" ncaj="" qha="" ntawm="" 0.12="" (95="" feem="" pua="" ​​​​ci:="" 0.26="" txog="" 0.02;="" p="" ¼="" 0.09)="" thiab="" 8="" feem="" pua="" ​​(95="" feem="" pua="" ​​ci:="" 2="" feem="" pua="" ​​​​rau="" 8="" feem="" pua)="" kev="" sib="">

Cistanche tuaj yeem txhim kho lub raum ua haujlwm

Kev sib tham

Hauv qhov kev tshawb fawb no, peb pom tias ntsev, thiab tsis noj cov protein, yog txuam nrog rau lub raum kev ua haujlwm poob hauv ADPKD. Cov nyhuv yog qhov cuam tshuam loj heev los ntawm qib plasma copeptin, qhia tias kev noj ntsev tuaj yeem ua rau muaj kev cuam tshuam los ntawm kev nce vasopressin.

Kev sib koom ua ke ntawm kev noj ntsev nrog eGFR poob yog nyob rau hauv txoj kab nrog qhov tsis txaus ua ntej fifindings. Ib qho kev koom tes ntawm sodium excretion thiab ADPKD kab mob kev loj hlob yog thawj zaug pom nyob rau hauv CRISP cohort, qhov twg ib tug tseem ceeb koom haum nrog rau lub raum ntim loj hlob tau pom.5 Nyob rau hauv multivariable tsom xam, ib tug tseem ceeb koom haum nrog eGFR poob tsis pom. Txawm li cas los xij, qhov no yog ib pawg ntawm cov neeg mob uas muaj ADPKD thaum ntxov uas GFR tseem tsis tau pib poob qis. Nrhiav cov koom haum nrog tus nqi ntawm eGFR poob rau hauv pawg neeg li no yog qhov nyuaj. Sodium excretion nyob rau hauv CRISP cohort yog siab dua nyob rau hauv peb pawg (193 86 vs. 156 65 mmol / 24 teev). Ib yam li ntawd, hauv kev soj ntsuam tom qab hoc ntawm HALT-PKD txoj kev tshawb no A, uas suav nrog cov neeg mob nrog ADPKD thaum ntxov, kev sib koom ua ke ntawm kev noj ntsev thiab eGFR poob qis tsis tseem ceeb (P ¼ 0.09). Hloov pauv, hauv HALT-PKD txoj kev tshawb fawb B (uas suav nrog cov neeg mob tom qab-theem ADPKD, qhov nruab nrab sodium excretion yog 178 80), kev koom tes ntawm ntsev kom tsawg nrog eGFR poob tau taw qhia rau cov txiaj ntsig zoo ntawm kev txwv ntsev.6 Peb tau lees paub qhov no. nrhiav nyob rau hauv ib pawg ntawm cov neeg mob nrog ADPKD nrog ntau yam ntawm lub raum ua haujlwm. Nyob rau hauv pawg neeg tam sim no, muaj qhov tseem ceeb tshaj qhov nruab nrab ntsev kom tsawg (thiab qhov sib txawv) hauv cov neeg mob hluas dua li cov neeg laus. Qhov no tej zaum yuav pab tau kom nrhiav tau ib tug qauv mus rau ib tug tseem ceeb heev kev sib raug zoo ntawm ntsev kom tsawg thiab eGFR poob nyob rau hauv pab pawg neeg no.

Hauv txoj kev xav, kev noj cov protein tuaj yeem ua rau muaj kev cuam tshuam los ntawm vasodilatory cov teebmeem uas ua rau intraglomerular hyperfiltration lossis los ntawm kev nce hauv vasopressin.13–15 Rau peb qhov kev paub, tsuas yog 2 txoj kev tshawb fawb soj ntsuam kev sib koom ntawm cov protein kom tsawg thiab eGFR poob hauv ADPKD. Zoo ib yam li sodium excretion, nyob rau hauv CRISP cohort tsis muaj kev koom tes tseem ceeb ntawm urea excretion thiab lub raum kev ua haujlwm poob qis yuav tshwm sim.5 Ib qho kev soj ntsuam tom qab hoc ntawm txoj kev tshawb fawb MDRD kuj tsis tau qhia txog qhov tseem ceeb ntawm cov khoom noj muaj protein tsawg ntawm eGFR nqes hav hauv ADPKD. .12 Txawm li cas los xij, cov neeg tshawb xyuas qhia tias qhov no yuav yog vim qhov mob hemodynamic cuam tshuam ntawm kev noj cov protein tsawg, uas ua rau muaj kev txo qis ntawm GFR. Qhov kev cuam tshuam no yuav ua rau muaj txiaj ntsig zoo tom qab ntawm GFR poob qis vim qhov kev soj ntsuam tsis ntev txaus.11 Tsis tas li ntawd, cov neeg tshawb xyuas qhia tias lawv yuav tsis muaj lub zog los qhia cov txiaj ntsig.11 Ib qho txiaj ntsig ntawm kev soj ntsuam ntawm peb. kev kawm yog qhov tsis muaj kev cuam tshuam ntawm kev noj zaub mov. Yog li, qhov mob hemodynamic tsis tuaj yeem piav qhia vim li cas peb tsis pom kev koom tes nroglub raum ua haujlwm poob qis. Txawm hais tias peb tsis tuaj yeem txwv tsis pub tsis muaj zog raws li kev piav qhia txog kev tsis pom kev sib koom ua ke ntawm cov protein kom tsawg thiab eGFR poob, kuj tsis zoo li yuav muaj kev sib koom tes zoo tom qab kev hloov kho rau cov neeg muaj peev xwm confounders, uas ua rau nws tsis tshua muaj.

Ib txoj hauv kev kho kom haum xeeb ntawm cov txiaj ntsig ntawm kev noj ntsev rau kev loj hlob ntawm tus kab mob tuaj yeem yog los ntawm ntshav siab. Salt-sensitive hypertension yog muaj nyob rau hauv CKD. Tsis tas li ntawd, qhov kev sim HALT-PKD tau pom muaj txiaj ntsig zoo ntawm kev tswj ntshav siab nruj txog TKV kev loj hlob hauv ADPKD thiab tseem hais txog eGFR poob qis hauv pawg neeg mob uas muaj kab mob hnyav tshaj plaws.16,17 Tseeb, hauv peb txoj kev tshawb fawb, muaj ib qho Kev sib koom tsis zoo ntawm cov ntshav siab thiab eGFR poob. Txawm li cas los xij, peb tsis muaj peev xwm qhia tau tias muaj kev koom tes tseem ceeb ntawm kev noj ntsev thiab ntshav siab. Nyob rau hauv txoj kab nrog cov txiaj ntsig no, kev txheeb xyuas kev sib kho tsis tau qhia qhov tseem ceeb ntawm kev sib haum xeeb los ntawm systolic ntshav siab.

Lwm lub tswv yim uas tau hais kom ua rau muaj txiaj ntsig zoo ntawm kev txwv ntsev kom tsawg ntawm ADPKD kab mob kev loj hlob yog qhov muaj zog ntawm RAAS blockade.6 Ib qho kev soj ntsuam tom qab ntawm Irbesartan Diabetic Nephropathy Trial (IDNT) thiab txo qhov kawg ntawm NIDDM Nrog Angiotensin II. Cov kev tshawb fawb Antagonist Losartan (RENTAL) tau pom tias kev noj zaub mov qis qis ua kom muaj txiaj ntsig zoo ntawm RAAS blockade hauv 1137 cov neeg mob ntshav qab zib nephropathy.18 Cov kev xav tias kev txwv ntsev potentiates lub raum tiv thaiv cov tshuaj tiv thaiv ntawm cov tshuaj no tau txais dav siv niaj hnub no. Txawm li cas los xij, yog tias muaj peev xwm ntawm RAAS blockade yuav yog qhov cuam tshuam ntawm ADPKD, peb yuav cia siab tias yuav muaj txiaj ntsig zoo ntawm kev txwv ntsev hauv RAAS blockade cov neeg siv dua li cov neeg mob uas tsis siv RAAS blockade. Raws li pom hauv daim duab 4, qhov no tsis yog qhov teeb meem; kev koom tes nrog kev noj ntsev ntau tshaj plaws hauv cov neeg mob uas tsis siv RAAS blockade. Kev muaj peev xwm ntawm RAAS thaiv, yog li ntawd, tsis zoo li yog lub hauv paus txheej txheem tom qab muaj txiaj ntsig zoo ntawm kev txwv ntsev hauv ADPKD. Peb tsis muaj peev xwm ua kom pom qhov cuam tshuam tseem ceeb ntawm renin lossis aldosterone hauv cov neeg mob uas tsis siv RAAS blockade; Txawm li cas los xij, peb tsis muaj lub zog txaus los kos cov lus xaus.

Peb tau pom qhov kev sib haum xeeb tseem ceeb ntawm kev noj ntsev los ntawm copeptin, tus cim tus cim ntawm vasopressin. Nws paub tias kev noj ntsev ntau ntxiv yuav ua rau muaj qhov nce hauv plasma osmolality, ua rau vasopressin secretion.10 Vice versa, hauv lawv cov kev tshawb fawb luv luv ntawm 34 cov neeg mob nrog ADPKD, Amro, thiab al.19 qhia tau hais tias ib qho kev sib xyaw ntsev thiab Kev txwv cov protein nyob rau hauv ua ke nrog kev kho dej kom tsawg tau ua rau txo qis hauv vasopressin secretion. Hauv CKD feem ntau, vasopressin tuaj yeem ua rau cov txheeb ze glomerular hyperfiltration uas muaj feem cuam tshuam.20 Hauv ADPKD tshwj xeeb, vasopressin ua rau cystogenesis thiab cuam tshuam nrog GFR poob.19 Kev kho mob nrog antagonists ntawm vasopressin V2 receptor ameliorate raum kev loj hlob thiab eGFR decline. 9 Hauv txoj kev tshawb fawb tam sim no, tsis pom qhov kev sib haum xeeb tseem ceeb ntawm plasma copeptin cuam tshuam ntawm eGFR poob los ntawm htTKV kev loj hlob qhia tias qhov cuam tshuam tsis zoo ntawm copeptin feem ntau tsis yog qhov tshwm sim ntawm kev loj hlob cyst. Kev kho kom haum xeeb ntawm cov tshuaj ntsev ntawm eGFR poob los ntawm vasopressin kuj tseem tuaj yeem piav qhia tsis pom qhov cuam tshuam ntawm kev noj cov protein. Cov kev sim tau pom tias urea yog ib qho tsis muaj txiaj ntsig osmole hauv cov ntshav: uas yog, qhov kev tso dej ntawm sodium ua rau muaj kev nce hauv vasopressin ntau dua li qhov sib npaug ntawm osmoles ntawm urea yuav.10 Yog tias urea tsis muaj kev cuam tshuam rau vasopressin, thiab qhov sib npaug ntawm cov osmoles ntawm urea yuav. Kev puas tsuaj ntawm cov khoom noj khoom haus hauv ADPKD feem ntau yog los ntawm vasopressin, ib tus yuav tsis cia siab tias yuav muaj kev cuam tshuam rau kev noj cov protein.

Cistanche tuaj yeem tonify raum

Muaj kev txwv rau txoj kev tshawb no uas yuav tsum tau hais txog. Vim tias tsis muaj kev noj zaub mov zoo, tej zaum yuav muaj kev hloov pauv ntawm cov ntsev thiab cov protein kom tsawg ntawm cov kev kawm thaum lub sijhawm kawm, uas yuav ua rau muaj kev cuam tshuam tsis zoo nrog cov kab mob sib kis. Vim li ntawd, peb siv qhov nruab nrab qhov tseem ceeb ntawm tag nrho 24- teev tso zis uas tau sau thoob plaws hauv txoj kev tshawb no. Qhov nruab nrab excretions yog tej zaum ib tug tsim nyog ntsuas ntawm nruab nrab kom tsawg. Tsis tas li ntawd, vim qhov kev soj ntsuam ntawm qhov kev tshawb fawb no, tsis tuaj yeem muaj cov lus xaus meej txog kev ua txhaum cai.

Lub zog tseem ceeb ntawm txoj kev tshawb fawb no suav nrog kev mus saib xyuas tas li, tso cai rau kev kwv yees eGFR txoj kab nqes kom raug, thiab kev kwv yees ntawm cov protein thiab ntsev kom tsawg los ntawm kev ntsuas kub: uas yog, los ntawm kev sau los ntawm ntau yam 24- teev cov zis kuaj ntau dhau. tag nrho lub sijhawm kawm. Cov kev tshawb fawb yav dhau los tau qhia tias ntau qhov 24- teev sau yuav tsum tau kom tau txais cov koom haum raug, thiab peb tau txais qhov nruab nrab ntawm 5 (IQR: 4, 7) cov qauv rau ib tus neeg mob.21 Thaum kawg, qhov no yog thawj txoj kev tshawb fawb uas qhia txog kev sib koom tes. nruab nrab ntawm kev noj ntsev thiab eGFR txoj kab nqes hauv ib pawg uas cov neeg mob uas muaj theem ntxov thiab cov neeg mob tom qab ADPKD yog ob qho tib si sawv cev zoo.

Peb qhov kev tshawb pom tias 1 g ntawm kev noj ntsev yog txuam nrog 0.11 ml / min ntawm 1.73 m2 txhua xyoo kev hloov pauv hauv eGFR qhia tias kev ua raws li cov lus qhia txog kev txwv sodium tam sim no tuaj yeem cuam tshuam cov kab mob raum kawg. Yog tias tus txiv neej muaj hnub nyoog 30- tus neeg mob uas muaj eGFR ntawm 110 ml / min ib 1.73 m2 yuav ua raws li qhov tam sim no qhia txog qhov siab tshaj plaws ntawm 5 g ntawm ntsev ib hnub, es tsis txhob ntawm 9.1 g (qhov nruab nrab hauv pawg no), nws yuav hypothetically ameliorate nws txhua xyoo hloov nyob rau hauv eGFR los ntawm 3.50 ml / min ib 1.73 m2 ib xyoo (nruab nrab nyob rau hauv no cohort) mus rau 3.05 ml / min ib 1.73 m2 ib xyoos twg. Tus neeg mob hypothetical no yuav ncuakab mob raum kawglos ntawm 4 xyoos, txij li hnub nyoog 57 txog 61. Qhov kev xav no xav tau kev pom zoo hauv kev tshawb nrhiav kev cuam tshuam. Raws li cov pab pawg no suav nrog ob peb tus neeg mob uas muaj kev kwv yees qis heev, peb tsis tuaj yeem tshawb xyuas cov txiaj ntsig ntawm kev noj cov sodium tsawg thiab yog li tsis tuaj yeem pom zoo rau kev txwv sodium tsawg dua li cov lus qhia tam sim no. Raws li peb cov ntaub ntawv, tsis muaj qhov qhia tau tias kev txwv cov protein muaj txiaj ntsig. Cov txiaj ntsig ntxiv ntawm kev txwv ntsev tuaj yeem yog txo qis ntawm polyuria ob qho tib si nyob rau theem kawg ADPKD thiab hauv cov neeg mob siv vasopressin V2 receptor antagonist tolvaptan. Nyob rau hauv ob qho tib si, osmolar excretion yog lub ntsiab txiav txim ntawm cov zis ntim vim cov zis concentrating defects.22 Txawm hais tias kev noj cov protein thiab ntsev kom tsawg muaj cov txiaj ntsig zoo ib yam ntawm kev txo cov polyuria tseem yog cov kev kawm yav tom ntej.

Hauv kev xaus, txoj kev tshawb no qhia tau hais tias 24- teev tso zis sodium yog cuam tshuam nrog tus nqi ntawm eGFR poob hauv ADPKD thiab qhia tias kev txwv ntsev yuav tsum yog qhov tseem ceeb ntawm cov kws kho mob hauv kev kho ADPKD.

Txoj kev

Rau txoj kev tshawb no, peb tau siv cov ntaub ntawv ntawm DIPAK kev soj ntsuam kev tshawb fawb uas tau tsim los tshawb xyuas qhov kev kawm ntawm PKD. Txoj kev tshawb fawb no tau pib los txuas ntxiv cov neeg mob nrog ADPKD uas tau koom nrog hauv DIPAK 1 randomized tswj kev sim uas tau soj ntsuam cov nyhuv renoprotective ntawm somatostatin analog lanreotide (n ¼ 305). Kev suav nrog rau hauv pawg neeg soj ntsuam tau txuas ntxiv mus rau cov neeg mob ADPKD los ntawm qhov chaw kho mob sab nraud (n ¼ 489) thiab tseem txuas ntxiv mus. Cov ntaub ntawv tau sau tseg hauv University Medical Centers ntawm Groningen, Leiden, Nijmegen, thiab Rotterdam. Kev tsim, cov txheej txheem, thiab cov txiaj ntsig tseem ceeb ntawm DIPAK 1 mus sib hais tau luam tawm lwm qhov.23,24 Hauv luv luv, cov neeg mob tau suav nrog ntawm 2012 thiab 2015 yog tias lawv muaj hnub nyoog 18 txog 60 xyoo, muaj ADPKD (hloov Ravine cov qauv 25), thiab eGFR ntawm 30 thiab 60 ml / min rau 1.73 m2. Tom qab kev mus ntsib kws kho mob, cov neeg mob tau pom ntawm 4, 8, 12, 48, 96, 120, thiab 132 lub lis piam, thiab cov ntshav tau sau txhua 12 lub lis piam. Tom qab qhov kawg ntawm qhov kev sim, 175 tus neeg mob tau pom zoo los txuas ntxiv mus ntxiv. Cov txheej txheem suav nrog rau txoj kev tshawb fawb soj ntsuam yog hnub nyoog $ 18 xyoo thiab eGFR ntawm $ 15 ml / min ib 1.73 m2. Txog thaum Lub Kaum Ob Hlis 31, 2017, txhua tus neeg mob tsim nyog uas tau pom ntawm cov chaw kho mob sab nraud ntawm ib qho ntawm 4 lub chaw tau thov kom koom nrog hauv kev soj ntsuam. Contraindications rau kev koom tes nyob rau hauv lub sim thiab soj ntsuam cohort yog concomitant kab mob los yog kev siv tshuaj uas yuav cuam tshuam rau lub ntuj txoj kev ntawm ADPKD (xws li, ntshav qab zib mellitus los yog ntev nonsteroidal anti-inflammatory tshuaj siv). Rau qhov kev tshuaj ntsuam xyuas tam sim no, peb suav nrog cov neeg mob ADPKD nrog tsawg kawg ntawm eGFR kev ntsuam xyuas ntawm 3 lub sijhawm tsawg kawg 2 xyoos ntawm kev soj ntsuam, tawm hauv 589 tus neeg mob rau kev tsom xam (Tshaj Tshaj Tawm Txog Kev Tshawb Fawb Kev Tshawb Fawb hauv Epidemiology [STROBE] flow diagram, Daim duab 1). Txoj kev tshawb fawb DIPAK tau pom zoo los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Tshawb Fawb ntawm University Medical Center Groningen thiab tau ua raws li International Conference on Harmonization-Good Clinical Practice Guidelines. Sau ntawv tso cai tau txais los ntawm txhua tus neeg mob.

Kev ntsuas

Creatinine tau ntsuas los ntawm isotope dilution mass spectrometry-traceable enzymatic method hauv cov qauv khaws cia ntawm {{{0}}C. eGFR tau kwv yees siv creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.26 Fasting plasma copeptin concentrations are measured using a sandwich immunoassay (B‧R‧A‧H‧M‧S, Thermo Fisher Scientific, Berlin, Lub teb chaws Yelemees), ntawm lub hauv paus ntawm txhua tus neeg mob thiab tseem nyob rau lub lim tiam 12 hauv cov neeg mob hauv DIPAK 1 txoj kev tshawb fawb. Renin (Renin III Generation RIA; Cisbio Bioassays, Codelet, Fabkis) thiab aldosterone (Demeditec Diagnostics GmbH, Kiel, Lub teb chaws Yelemees) tau ntsuas ntawm lub hauv paus los ntawm radioimmunoassay. Osmolality tau ntsuas los ntawm qhov chaw txias txias txoj kev nyuaj siab, sodium thiab potassium concentration los ntawm ion tshwj xeeb electrodes, thiab urea los ntawm kev soj ntsuam enzyme kinetic. Sib nqus resonance imaging tau ua los ntawm kev siv cov txheej txheem sib nqus resonance imaging raws tu qauv yam tsis siv qhov sib txawv ntawm cov hlab ntsha. TKV tau soj ntsuam los ntawm phau ntawv taug qab ntawm T2- hnyav coronal magnetic resonance dluab siv Analyze ncaj qha 9.0 software (Ana lyzeDirect, Inc., Overland Park, KS).

24- teev tso zis

Nees nkaum plaub-teev cov zis kuaj tau muab khaws cia ntawm qhov pib; nyob rau lub lis piam 12, 48, 96, 120, thiab 132; thiab nyob rau hauv cov ntaub ntawv ntawm qhov kawg ntawm kev kho mob thaum lub sij hawm DIPAK 1 mus sib hais thiab txhua xyoo tom qab ntawd. Rau txhua qhov kev ntsuam xyuas, qhov nruab nrab qhov tseem ceeb ntawm txhua qhov muaj 24- teev cov zis tau siv. Sodium tau ntsuas los ntawm ion-txheej electrodes thiab urea los ntawm enzyme kinetic assay. Kev noj ntsev tau kwv yees los ntawm kev sib npaug ntawm sodium excretion los ntawm qhov sib npaug ntawm molar pawg ntawm sodium thiab chloride: ntsev kom tsawg ¼ sodium excretion (mol) (22.99 þ 35.45). Tag nrho cov protein kom tsawg tau kwv yees los ntawm urea excretion los ntawm txoj kev Maroni li al.27: protein kom tsawg ¼ [urea excretion (mmol) 0.028 þ 0.031 lub cev hnyav (kg)] 6.25.

Kev txheeb cais

Rau kev txheeb xyuas kev txheeb cais, peb siv SPSS version 23 (IBM Corp., Armonk, NY) lossis Stata SE 14 (StataCorp, College Station, TX) nyob rau hauv rooj plaub ntawm linear mixed qauv analyses. Rau txhua qhov kev ntsuam xyuas, ib qho 2-sided P < 0.05="" tau="" suav="" tias="" yog="" qhov="" tseem="">

Cov qauv sib xyaw ua ke rov ntsuas ntsuas tau siv los ntsuas cov koom haum ntawm kev noj zaub mov noj nrog txoj kab nqes ntawm eGFR txoj kab nqes, thiab tag nrho cov kev ntsuas eGFR muaj nyob rau hauv kev tsom xam txoj kab nqes. Rau sodium thiab urea excretions, qhov nruab nrab qhov tseem ceeb ntawm tag nrho cov muaj 24- teev cov zis sau tau siv. Kev cuam tshuam thiab txoj kab nqes tau tso cai rau qhov sib txawv ntawm qhov sib txawv, nrog rau qhov tsis sib xws ntawm cov qauv sib txawv. Tsau cov teebmeem hauv cov qauv yog lub sijhawm, sodium excretion (lossis kwv yees kev noj ntsev), BSA, hnub nyoog, poj niam txiv neej, htTKV, thiab DNA hloov pauv, nrog rau kev sib cuam tshuam ntawm cov kev hloov pauv nrog lub sijhawm. Lub sijhawm sib cuam tshuam tseem ceeb ntawm sodium excretion qhia txog kev koom tes nrog eGFR poob txhua xyoo. Cov kev soj ntsuam zoo sib xws tau ua rau urea excretion (los yog kwv yees cov protein kom tsawg). Cov neeg mob tau suav nrog hauv kev tshuaj xyuas ntawm tag nrho cov ntaub ntawv muaj nyob rau hauv listwise (ua tiav cov ntaub ntawv tsom xam). Kev ua raws li kev sib nqus resonance imaging tau ua thaum lub sij hawm DIPAK 1 mus sib hais. Kev hloov pauv hauv htTKV tau raug ntsuas los ntawm kev siv lub log10- hloov pauv htTKV

cov ntaub ntawv, cov antilog ntawm qhov kwv yees cov txiaj ntsig tau muab los ntawm cov qauv sib xyaw ua ke los muab cov kev hloov pauv txhua xyoo ntawm htTKV. Model validation yog ua los ntawm kev soj ntsuam pom ntawm cov seem seem. Peb npaj cov histograms ntawm qib 1 seem thiab histograms ntawm cov seem ntawm cov random slopes thiab intercepts. Standardized residuals tau plotted piv rau kwv yees tus nqi thiab lub sij hawm.

We performed a number of sensitivity analyses. Salt and protein intake were corrected for actual body weight and ideal body weight. Ideal body weight was derived using a body mass index of 22 kg/m2 as reference. Furthermore, the analyses were repeated excluding the 142 patients who received lanreotide treatment during the DIPAK 1 trial. We also performed sensitivity analyses to investigate the effect of urine collection errors. We repeated the analyses with median urinary excretion values instead of the mean, and we excluded follow-up urine collections if creatinine excretion was >30 feem pua ​​txawv ntawm qhov nruab nrab. Thaum kawg, peb tau ua qhov kev soj ntsuam rhiab heev uas peb siv lub hauv paus 24- teev cov zis sau los ntawm

nruab nrab, thiab peb tau ua qhov kev soj ntsuam rhiab heev uas peb tau kho rau albuminuria.

Cistanche tuaj yeem tiv thaiv kab mob raum

Cov qauv sib npaug ntawm cov qauv siv los ua qhov kev sib kho kom haum xeeb nrog eGFR txoj kab nqes raws li qhov tshwm sim sib txawv; kwv yees kev noj ntsev raws li qhov raug; thiab systolic ntshav siab, plasma copeptin, plasma renin, thiab plasma aldosterone ua cov neeg tuaj yeem kho tau. Rau copeptin, qhov nruab nrab ntawm 2 qhov ntsuas tau siv rau kev kho kom haum xeeb. Copeptin tau hloov pauv hauv lub cev. Kev tshuaj xyuas kev sib haum xeeb nrog plasma renin thiab aldosterone tsuas yog ua rau cov neeg mob uas tsis siv RAAS blockade. eGFR txoj kab nqes thiab cuam tshuam tau ntxiv raws li qhov hloov pauv tsis zoo. Nyob rau hauv sib piv rau longitudinal mix-effects qauv, latent kev loj hlob tus qauv sib npaug qauv yuav tsum tau cov ntaub ntawv lub sij hawm-structured (ie, cov ntaub ntawv sau tib lub sij hawm los ntawm lub hauv paus rau txhua yam kev kawm). Yog li, cov ntaub ntawv los ntawm DIPAK kev soj ntsuam kev tshawb fawb tsis tuaj yeem ua ke nrog cov ntaub ntawv los ntawm DIPAK 1 mus sib hais, thiab tsuas yog cov ntaub ntawv khaws tseg thaum lub sijhawm DIPAK 1 mus sib hais tau suav nrog hauv qhov kev tshuaj ntsuam no. Tib qhov kev tshuaj ntsuam tau rov ua dua nrog htTKV kev loj hlob raws li qhov txiaj ntsig sib txawv.

Nyob rau hauv cov ntaub ntawv ntawm qhov kev sib haum xeeb tseem ceeb ntawm txoj kab nqes eGFR, peb tau tshawb xyuas lub luag haujlwm ntawm qhov muaj peev xwm ntsuas thiab tsis ntsuas qhov tsis sib haum xeeb. Raws li qhov muaj peev xwm confounders, peb ntsuas hnub nyoog, poj niam txiv neej, BSA, lub hauv paus eGFR, lub hauv paus TKV (log{{0}}} hloov pauv), DNA hloov pauv (PKD1 lossis PKD2), kev siv RAAS thaiv, thiab siv cov tshuaj diuretics. Peb tau soj ntsuam kev sib kis-tus neeg nruab nrab confounding, tus neeg nruab nrab-qhov tshwm sim tsis meej pem, thiab kev cuam tshuam-tus neeg nruab nrab tsis meej pem. Siv cov qauv sib npaug sib npaug, peb kwv yees cov koom haum tsis sib xws ntawm cov muaj peev xwm confounders nrog tus neeg nruab nrab thiab cov txiaj ntsig. Tom qab ntawd, peb ntxiv tag nrho cov muaj peev xwm confounders uas yog univariably txuam nrog ib tug multivariable qauv. Cov kev hloov pauv uas tau cuam tshuam nrog kev cuam tshuam los yog qhov tshwm sim hauv kev txheeb xyuas ntau yam sib txawv (P <0.05) tom="" qab="" tshem="" tawm="" rov="" qab="" tau="" suav="" nrog="" hauv="" cov="" qauv="" kev="" sib="" npaug="" sib="" npaug.="" qhov="" cuam="" tshuam="" ntawm="" kev="" ntsuas="" tsis="" pom="" kev="" tsis="" txaus="" ntseeg="" tau="" raug="" ntsuas="" los="" ntawm="" kev="" soj="" ntsuam="" rhiab="" heev,="" raws="" li="" txoj="" kev="" ntawm="" imai="" li="">

Kev soj ntsuam pab pawg tau ua rau kev sib koom ua ke ntawm kev noj ntsev thiab eGFR txoj kab nqes los ntawm kev suav nrog cov lus sib cuam tshuam ntawm pawg pab pawg thiab kev noj ntsev (qib pawg ntsev) hauv cov qauv sib txawv sib txawv, hloov kho rau hnub nyoog, poj niam txiv neej, thiab BSA. Yog tias lub sijhawm sib cuam tshuam tseem ceeb, pawg pab pawg tau suav tias yog tus neeg saib xyuas tseem ceeb rau lub koom haum.

Qhia tawm

Cov kws sau ntawv tau txais cov nyiaj pab tsis pub dhau los ntawm Ipsen (tus tsim khoom ntawm somatostatin analog) raws li kev sib koom tes nyiaj txiag rau tus neeg tshawb nrhiav-tsav randomized, tswj kev sim (DIPAK 1 txoj kev kawm).

TXOJ CAI

DIPAK Consortium yog kev sib koom tes hauv tsev kawm qib siab hauv Netherlands uas tau tsim los kawm ADPKD thiab tsim cov tswv yim kho mob rau tus kab mob no. Lub koom haum DIPAK tau txhawb nqa los ntawm Health Holland, Dutch raum Foundation (nyiaj pab CP10.12 thiab CP15.01), thiab Dutch tsoom fwv (nyiaj pab LSHM15018). Txoj kev tshawb fawb tam sim no tau txhawb nqa los ntawm Dutch Kidney Foundation (grant 18OKG04).

TSEEM CEEB

MATERIAL Supplementary File (Lo lus)

Daim duab S1. Scatterplot ntawm kev ntsuas copeptin ntawm lub hauv paus thiab lub lim tiam 12.

Tab S1. Kev ntsuam xyuas rhiab heev: cov koom haum nrog txoj kab nqes ntawm kwv yees GFR.

TableS2. Cov yam ntxwv tseem ceeb ntawm cov neeg mob uas siv RAAS blockade thiab cov neeg mob uas tsis siv RAAS blockade.

Tab S3. Kev soj ntsuam rhiab heev ntawm kev sib kho.

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