Ib tug Tshiab Pillar Ntawm Raum-Lub Plawv Kho Rau CKD Teeb Nrog T2DM

Thaum Lub Rau Hli 15-18, 2023, 60th European Renal Association (ERA) Congress tau ua tiav hauv Milan, Ltalis hauv kev sib txuas ntawm online thiab offline. Lub rooj sib tham tau sau ntau dua 9,000 cov kws tshawb fawb los ntawm thoob plaws lub ntiaj teb los tham txog kev txhim kho tshiab thiab kev tshawb fawb txog kab mob raum. Cov ntsiab lus hais txog kev kho mob raum, cov tshuaj yooj yim, mob ntshav qab zib nephropathy, thiab lwm yam, muab lub sijhawm kawm tsis tshua muaj rau cov neeg ua haujlwm kho mob.

Nyem rau cistanche tubulosa ntau npaum rau mob raum

Feem ntau ntawm cov kab mob raum ntev (CKD) ua ke nrog hom 2 mob ntshav qab zib mellitus (T2DM) yog siab, uas ua rau muaj kev hem thawj rau lub neej thiab kev noj qab haus huv ntawm cov neeg mob. Hauv lub rooj sib tham ERA no, xibfwb Giuseppe Grandaliano los ntawm Ltalis tau ua tus thawj coj hauv lub rooj sib tham ntawm "Non-Steroidal MRAs: Ib Pillar ntawm Lub Raum-Lub Plawv Kho Mob rau CKD Teeb meem nrog T2DM", tsom mus rau "Cov Lus Qhia Kev Pom Zoo Hloov Kho rau Tsis-Steroidal MRA" Cov. Peb lub ntsiab lus ntawm "kev thov thaum ntxov ntawm non-steroidal MRA" thiab "ob npaug txiaj ntsig ntawm non-steroidal MRA rau lub raum thiab lub plawv" tau qhia.

Tus tshiab uas tsis yog-steroidal MRA ncaj qha tawm tsam cov ntsiab lus ntawm tus kab mob, pab CKD ua ke nrog T2DM kom muaj txiaj ntsig rau ob lub raum thiab lub plawv.

Hauv 40 xyoo dhau los, kev kho mob ntawm CKD ua ke nrog T2DM tau tsim kho zoo heev. Yav dhau los, kev tswj ntshav siab tau sawv cev los ntawm renin-angiotensin system inhibitors (RASi) thiab sodium-glucose co-transporter 2 inhibitors (SGLT2i) Txawm hais tias tus neeg sawv cev ntawm cov ntshav qabzib tswj tau txhim kho lub peev xwm ncua kev nce qib ntawm CKD mus rau qee yam. , qhov seem ntawm lub raum thiab mob plawv tseem muaj siab, thiab lub raum kev loj hlob tseem tsis tau nres kiag li 1. Hauv kev sib tham no, xibfwb Beatriz Fernández-Fernández los ntawm Spain thawj zaug tau hais txog qhov tseem ceeb ntawm cov tshuaj kho tshiab lub hom phiaj mineralocorticoid receptor (MR) hauv CKD ua ke nrog T2DM kab mob thiab taw qhia tias MR nyob hauv plawv, lub raum, thiab vascular system overactivation tuaj yeem ua rau Kev kho cov ntaub so ntswg, kev ua haujlwm tsis zoo, o, thiab fibrosis2, yog li ntawd, inhibition ntawm MR overactivation yog ib qho tseem ceeb kho lub tswv yim los txhim kho lub raum mob, fibrosis, thiab txo cov hlab plawv. Cov tshiab uas tsis yog-steroidal xaiv MRA finerenone tuaj yeem ncaj qha, raug, thiab ua tiav antagonize lub overactivation ntawm MR, thaiv qhov mob thiab fibrosis ntawm lub raum thiab lub plawv, thiab nqa ob qho txiaj ntsig rau cov neeg mob3. Nws tau dhau los ua tus ncej tshiab hauv kev kho CKD ua ke nrog T2DM. Tsis tas li ntawd, cov qauv tshiab ntawm finerenone muaj txiaj ntsig zoo hla qhov tsis txaus ntawm cov tshuaj steroidal MRA hauv ntau yam xws li cov qauv molecular, kev ua tau zoo, thiab kev nyab xeeb, thiab nws muaj zog thiab muaj kev nyab xeeb zoo dua thiab kam rau ua3.

Raws li cov txheej txheem tshwj xeeb ntawm kev txiav txim, qhov kev kho mob ua tau zoo ntawm finerenone tau raug tshawb xyuas tag nrho. Thawj theem III txoj kev tshawb fawb FIDELIO-DKD tau lees paub tias finerenone tuaj yeem ncua kev loj hlob ntawm cov kab mob hauv lub raum thiab txo qhov tshwm sim ntawm cov xwm txheej CV hauv cov neeg mob uas muaj mob me me mus rau CKD nyuaj nrog T2DM4. Tom qab ntawd, lwm qhov kev tshawb fawb loj III, FIGARO-DKD, tau muab cov pov thawj muaj zog rau cov txiaj ntsig ntawm lub raum thiab lub plawv hauv cov neeg mob thaum ntxov CKD thiab T2DM (Daim duab 1). Tsis tas li ntawd, txoj kev tshawb nrhiav thaj av FIDELITY yog ib qho kev tshuaj ntsuam xyuas ntawm finerenone FIDELIO thiab FIGARO kev tshawb fawb, thiab nws kuj yog qhov loj tshaj plaws theem III txoj kev kawm ntawm CKD ua ke nrog T2DM nyob rau hauv lub ntiaj teb no thiab cov kev pab cuam ntau tshaj ntawm cov pejxeem, npog CKD theem {{7 } }, urinary albumin Rau ntau tus neeg uas muaj creatinine piv (UACR) ntawm 30-5000 mg/g, cov kev tshawb fawb tau pom tias raws li kev kho RASi ntau tshaj plaws thiab ua tiav cov ntshav siab thiab ntshav qab zib cov hom phiaj, finerenone tseem tuaj yeem txuas ntxiv. txo qhov kev pheej hmoo ntawm lub raum sib xyaw endpoints los ntawm 23 feem pua. , txo qhov kev pheej hmoo ntawm cov hlab plawv endpoints los ntawm 14 feem pua ​​6. Los ntawm nws cov txheej txheem tshwj xeeb ntawm kev ua, finerenone ncaj qha hits cov ntsiab lus ntawm tus kab mob thiab paub txog cov txiaj ntsig ntawm ob lub raum thiab lub plawv. Nws tau dhau los ua tus ncej tshiab rau kev kho mob CKD ua ke nrog T2DM uas ncaj qha rau kev tswj hwm cov proteinuria tom qab ntshav qab zib thiab tswj ntshav siab.

Daim duab 1 FIDELIO-DKD thiab FIGARO-DKD kev tshawb fawb: finerenone muaj ob lub raum thiab lub plawv

Kev siv cov finerenone thaum ntxov tuaj yeem txhim kho cov kev mob tshwm sim ntawm cov neeg mob

CKD ua ke nrog T2DM yog qhov ua rau lub raum tsis ua haujlwm kawg. Thaum tus neeg mob nkag mus rau theem proteinuric, lub raum kev puas tsuaj yog qhov nyuaj rau thim rov qab, qhia txog qhov tseem ceeb ntawm kev kho mob thaum ntxov. Cov lus qhia taw qhia tias yog tias CKD tuaj yeem kuaj pom thiab kho tau ntxov, tus kab mob tuaj yeem tswj tau zoo thiab txawm rov qab los.

Hauv lub rooj sib tham no, xibfwb Christoph Wanner los ntawm lub teb chaws Yelemees tau hais txog qhov tseem ceeb ntawm kev kho mob ntxov ntawm CKD ua ke nrog T2DM thiab tau txais txiaj ntsig ntawm kev kho mob thaum ntxov los ntawm ib rooj plaub. Xib fwb Rajiv Agarwal los ntawm Tebchaws Meskas kuj tau hais txog qhov tseem ceeb ntawm UACR hauv kev tswj hwm cov kab mob thaum ntxov los ntawm qhov xwm txheej no, taw qhia tias UACR, ua tus cim tseem ceeb ntawm kev raug mob raum thiab lub plawv thiab lub raum kev pheej hmoo, tuaj yeem tshwm sim thaum ntxov ntawm tus kab mob8. , thiab tuaj yeem siv rau hauv chaw kho mob tsis yog rau Kev kuaj thiab kuaj mob raum mob ntev 9-10 tuaj yeem ntsuas thiab kwv yees qhov kev loj hlob ntawm cov kab mob hauv lub raum thiab kev pheej hmoo ntawm cov hlab plawv tuag11-12, uas yog cov cim tseem ceeb rau cov siv cov tshuaj renoprotective. Ntau cov lus qhia hauv tsev thiab txawv teb chaws pom zoo kom saib xyuas albuminuria tsis tu ncua hauv cov neeg mob CKD thiab T2DM thiab coj kev tswj hwm albuminuria ua ib qho ntawm cov hom phiaj kho mob10,13-14. Xib fwb Rajiv Agarwal kuj tau txheeb xyuas FIGARO-DKD theem III txoj kev tshawb fawb ntawm finerenone. Ntawm cov neeg mob suav nrog hauv FIGARO-DKD txoj kev tshawb fawb, 62 feem pua ​​​​tau muaj albuminuria (qhov nruab nrab UACR 308 mg / g) tab sis lub raum kev ua haujlwm tseem tsis tau hloov pauv (eGFR Ntau dua lossis sib npaug li 60 ml / min / 1.73 ㎡), 46 feem pua ​​​​tau nrog nruab nrab. albuminuria nce (UACR 30 ~<300 mg/g), the results showed that after 4 months of finerenone treatment, UACR was significantly reduced by 32 % (HR 0.68; 95% CI, 0.65-0.70), and the effect was sustained (Figure 2). It is suggested that the management of finerenone on albuminuria is helpful to advance the treatment of CKD combined with T2DM, and provides an effective means for early intervention5.

Daim duab 2 FIGARO-DKD txoj kev kawm: Finerenone txo UACR

Xib fwb Rajiv Agarwal kuj tau taw qhia tias albuminuria, raws li tus kws tshaj lij ywj pheej ntawm kev mob raum thiab kab mob plawv, yuav tsum khiav los ntawm kev tswj hwm ntawm CKD ua ke nrog T2DM. Cov kev tshawb fawb tau pom tias rau txhua 30 feem pua ​​​​txo hauv UACR, qhov kev pheej hmoo ntawm lub raum kev loj hlob yuav raug txo los ntawm 27 feem pua ​​15 (Daim duab 3). Kev txhim kho ntawm UACR tuaj yeem tsis tsuas yog ncua sijhawm rau lub raum, tab sis kuj txo qis CV kev tuag thiab kev lim ntshav, ua kom tus neeg mob muaj sia nyob ntev, thiab txo cov nqi kho mob16. Cov kev tshawb fawb tau pom tias finerenone tuaj yeem txhim kho cov txiaj ntsig ntawm cov hlab plawv17 thiab txo qhov kev pheej hmoo ntawm CV tuag18 (Daim duab 4), thiab nws tsis cuam tshuam los ntawm cov hauv paus UACR.

Daim duab 3 UACR txo qis tuaj yeem ncua lub raum kev loj hlob

Daim duab 4 Finerenone txo qhov kev pheej hmoo ntawm CV ntsig txog kev tuag tsis hais tus neeg mob lub hauv paus UACR

Cov xwm txheej pom zoo ntawm cov lus qhia finerenone tseem nce ntxiv

Raws li cov ntaub ntawv pov thawj kev kho mob ntau, finerenone tau pom zoo los ntawm ntau cov kev cai lij choj suav nrog ADA, KDIGO, AHA, thiab AACE (Daim duab 5), thiab nws cov xwm txheej hauv thaj tsam ntawm CKD ua ke nrog T2DM tau nce tas li. Prof. Beatriz Fernández-Fernández piav qhia meej txog cov kev hloov pauv hauv US ADA cov lus qhia rau cov lus pom zoo finerenone (Daim duab 6), hais txog qhov tseem ceeb ntawm finerenone hauv kev kho mob ntawm CKD ua ke nrog T2DM. Nyob rau hauv 2022 tsab ntawm ADA Diabetes Diagnosis and Treatment Standards, hais txog kev kho mob ntawm CKD ua ke nrog T2DM, finerenone tau ua nws thawj zaug thiab tau pom zoo: Rau cov neeg mob CKD uas muaj kev pheej hmoo siab ntawm cov hlab plawv lossis CKD kev loj hlob, lossis leej twg tsis tuaj yeem siv SGLT2i, nws raug pom zoo kom siv cov tshuaj uas tsis yog Steroidal MRA finerenone los txo qhov kev pheej hmoo ntawm CKD kev loj hlob thiab cov kab mob plawv (qib A pom zoo) 9. Nyob rau lub Tsib Hlis 2022, ADA tau ntxiv qee cov ntsiab lus rau "kev kuaj mob ntshav qab zib thiab kev kho tus qauv": xav pom zoo finerenone rau cov neeg mob nrog. CKD thiab T2DM uas tau txais cov koob tshuaj siab tshaj plaws ntawm angiotensin-hloov enzyme inhibitor (ACEI) lossis angiotensin II receptor blocker (ARB) txhawm rau txhim kho cov kab mob plawv thiab txo qis kev pheej hmoo ntawm CKD kev loj hlob (Qib A Pom Zoo) 19. Lub Ib Hlis 2023, Qhov tseeb version ntawm "ADA Diabetes Diagnosis and Treatment Standards" tau tso tawm. Piv nrog rau yav dhau los version, qhov tshiab version ntawm cov lus qhia tau txhim kho cov xwm txheej ntawm non-steroidal MRA hauv kev tswj hwm ntawm CKD ua ke nrog T2DM, thiab nws raug pom zoo ua ke nrog lwm cov tshuaj raws li kev kho mob yooj yim los muab kev tiv thaiv lub raum thiab lub plawv, es tsis yog. Raws li lwm txoj kev kho mob thaum lwm yam kev kho mob tsis zoo, cov lus pom zoo tshwj xeeb yog: Rau cov neeg mob CKD nrog albuminuria uas muaj cov kab mob plawv lossis muaj kev pheej hmoo ntawm CKD, nws raug nquahu kom siv cov kev sim tshuaj ntsuam xyuas los ua pov thawj tias tsis yog-steroidal MRA kom ncua kev loj hlob. ntawm CKD thiab txo qhov tshwm sim ntawm cov kab mob plawv (Qib A pom zoo) 13 (Daim duab 2). Cov kev hloov pauv hauv ADA cov lus qhia rau kev pom zoo kev kho mob ntawm finerenone qhia txog qhov nce ntawm finerenone hauv kev kho mob daim ntawv thov thiab yuav pab tau ntau tus neeg mob nrog CKD thiab T2DM.

Daim duab 5 Finerenone tau pom zoo los ntawm ntau yam kev qhia thoob ntiaj teb

Daim duab 6 ADA cov lus qhia cov lus pom zoo rau finerenone tau hloov kho tas li

Cov ntsiab lus

Tau ntev, CKD ua ke nrog T2DM tau teeb meem kev noj qab haus huv ntawm kev txhawj xeeb thoob ntiaj teb. Txhim kho kev tswj hwm ntawm albuminuria, txhawb kev cuam tshuam ntxov ntawm tus kab mob, thiab kev siv cov tshuaj tshiab thaum ntxov nrog cov txiaj ntsig zoo rau lub raum thiab lub plawv yog txoj kev tswj hwm zoo rau CKD ua ke nrog T2DM. Cov non-steroidal MRA finerenone ncaj qha ua rau lub hom phiaj ntawm lub raum thiab lub plawv, ua kom muaj zog tiv thaiv kab mob thiab tiv thaiv fibrosis, txo qis albuminuria, ncua lub raum kev loj hlob thiab txhim kho CV prognosis. Raws li nws cov txheej txheem tshiab ntawm kev nqis tes ua thiab cov pov thawj kev kho mob ntau, nws tau txais ntau cov ntawv pov thawj thoob ntiaj teb pom zoo kom pab CKD ua ke nrog T2DM kom muaj txiaj ntsig rau ob lub raum thiab lub plawv.

Cistanche kho mob raum li cas?

Cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrog kab mob raum. Nws yog muab los ntawm cov stems qhuav ntawm Cistanche deserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Cov khoom tseem ceeb ntawm cistanche yog phenylethanoid glycosides, echinacoside, thiab acteoside, uas tau pom tias muaj txiaj ntsig zoo rau lub raum noj qab haus huv.

Kab mob raum, tseem hu ua kab mob raum, hais txog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tswv yim.

Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.

Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.

Tsis tas li ntawd, cistanche tau pom tias muaj cov nyhuv anti-inflammatory. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.

Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv kab mob raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho kev tsim khoom thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.

Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.

Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.

Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.

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