Overhydration: Ua rau Oran cuam tshuam rau lub raum puas thiab yuav kho li cas
Mar 16, 2022
Abstract
Volume overload tuaj yeem ua rau ob qho tib si ua rau thiab qhov tshwm sim ntawm kev mob ntevmob raum (CKD). Overhydration feem ntau nroglub raumtsis txaus. Hauv kab mob plawv (CVD), cov kua dej ntau dhau tuaj yeem ua raulub raum ua haujlwmkev puas tsuaj. Dhau li ntawm kev txwv ntsev, voj diuretics yog thawj kab kev kho mob. Kev txhim kho tsis tu ncua tuaj yeem kov yeej los ntawm kev hloov mus rau kev tswj hwm cov hlab ntsha, ntxiv albumin ib leeg lossis ua ke nrog lwm cov tshuaj diuretics. Cov xwm txheej tsis zoo xws li kev kis kab mob lossis qhov sib txawv ntawm cov xov xwm tuaj yeem cuam tshuam cov lus teb ntawm diuretic thiab ua rau muaj kev tsis haum tshuaj. Sib nrug los ntawm kev tswj hwm kev saib xyuas, ultrafiltration (UF) thiab peritoneal dialysis (PD) yog siv. Hauv kev mob loj heev nrog cov nyhuv diuretic tsis txaus, hemodialysis nrog UF plays lub luag haujlwm tseem ceeb raws li kev kho ib ntus lossis mus tas li. Cov ntaub ntawv ntau ntxiv qhia tau tias sodium-glucose cotransporter -2 inhibitors (SGLT2i) tau tso cai rau kev ua tiav ntawm kev tswj cov kua dej hauv cov neeg mob ntshav qab zib thiab cov neeg mob uas tsis muaj ntshav qab zib nrog CKD. Sodium-glucose cotransporter 2 inhibitors qhia cardio- thiab renoprotective teebmeem thiab muaj kev cuam tshuam zoo rau cov hlab plawv thiablub raumcov ntsiab lus kawg.
CISTANCHE yuav txhim kho lub raum / raum ua haujlwm
Taw qhia
Ib tus neeg mob uas pom cov ceg o, orthopnea, thiab ua pa luv nrog lub plawv tsis ua haujlwm (HF) lossis ntshav qab zib mellitus (DM) tuaj yeem tsim kev puas tsuaj ntawmlub raum ua haujlwm. Yog tias kho cov kua dej rov qab, tsis hais txog kev cuam tshuam, rov ua dualub raum ua haujlwm, peb tuaj yeem xav tias overhydration yog qhov ua raumob raum. Progressively declining glomerular filtration rate (GFR) nyob rau hauv chav kawm ntawmmob raumua rau muaj ntshav siab, sodium retention, thiab kua dej ntau dhau. Hauv cov neeg mob anuric, overhydration, raws li cov nyhuv ntawmraum puas, tuaj yeem ua rau muaj kev phom sij. Qhov xwm txheej tshwm sim ntau zaus yog qhov sib xyaw ntawm 2 qhov piv txwv tau hais, zoo tshaj plaws piav qhia raws li tus mob cardiorenal syndrome (CRS) nrog dej dhau los ua cov txiaj ntsig zoo. Hauv ob peb xyoos dhau los, cov ntaub ntawv tshiab hais txog yuav ua li cas kev kho dej overhydration tau txais txiaj ntsig tau raug luam tawm.
Ntsiab lus:mob raum mob, diuretics, dialysis, cardiorenal syndrome, SGLT2 inhibitors
Peb puas muaj cov ntaub ntawv zoo txaus hauv CKD?Circulatory system abnormalities tshwm sim feem ntau nyob rau hauv cov neeg mob uas mobmob raum(CKD). Kev haus dej ntau dhau yog ib qho ntawm cov tsos mob tshwm sim feem ntau los ntawm kab mob plawv (CVD) mob plawv tsis txaus. Hmoov tsis zoo, tseem tsis muaj cov ntaub ntawv txaus txaus kom nkag siab txog kev sib cuam tshuam ntawm cardiorenal. Qhov teeb meem yuav tsum tsis txhob poob qis, vim tias CKD nyob rau ntau theem cuam tshuam rau ntau dua 850 lab tus tib neeg thoob ntiaj teb, uas ua rau ob npaug ntshav qab zib thiab ntau dua nees nkaum npaug tshwm sim. Vim tias feem ntau cov kab mob tsis txaus ntseeg, ntau tus neeg mob tsis paub txog tsis yog ntawm CKD nws tus kheej nkaus xwb tab sis kuj muaj cov teeb meem tshwm sim, suav nrog CVD. Nws yuav tsum tau hais qhia tias yuav luag ib nrab ntawm cov neeg mob CKD tuag vim yog mob plawv loj.1
Cardiorenal syndromes
Overhydration tuaj yeem pom nyob rau hauv cov ntsiab lus ntawm cardiorenal crosstalk, uas yog bidirectional. Kev faib tawm ntawm lub cev sib cuam tshuam tau raug npaj los ntawm lub rooj sib tham pom zoo ntawm Acute Dialysis Quality Initiative hauv 2008.2 Ib pawg kws tshaj lij thiab cov thawj coj kev xav tau faib CRS rau hauv 5 chav kawm raws li cov hauv paus hauv paus pathology thiab nws tus cwj pwm mob lossis mob ntev: mob. cardiorenal syndrome (type 1), chronic cardiorenal syndrome (type 2), mob plawv reno cardiac syndrome (type 3), chronic reno-cardiac syndrome (type 4), thiab secondary cardiorenal syndromes (type 5). Lub voj voog vicious ntawm sodium thiab dej tuav yog ib qho cim ntawm CRS hom 2 uas nquag nquag (Fig. 1).
Txawm hais tias cov neeg mob plawv tuag ntawm cov neeg mob hemodialysis yog qhov nkag siab ntau dua, nws tau raug pov thawj tias txawm tias cov neeg mob nyob rau theem ua ntej ntawm CKD muaj kev pheej hmoo siab dua CVD.3 Ntawm CVDs, muaj cov neeg tuag triad: congestive HF, mob myocardial infarction (MI) thiab Tam sim no lub plawv tuag uas coj tus xov tooj loj tshaj plaws.4 Twb tau microalbuminuria, txawm tias muaj GFR khaws cia, hais txog kev tuag ntawm cov hlab plawv, 3 thiab kev cuam tshuam ntawm kwv yees glomerular filtration rate (eGFR) ntawm cov teeb meem tsis zoo ntawm cov hlab plawv tseem ceeb yog ncaj qha.5 Tsis tas li ntawd, tus neeg mob CKD tsis tshua muaj kev vam meej mus rau theem kawgmob raum(ESRD) dua li yuav dhau mus vim yog CVD.6 Raws li kev txheeb xyuas ntau yam suav nrog kev tshuaj xyuas cov ntaub ntawv loj uas muaj ntau tshaj li ib lab tus neeg mob, 7 nws yuav tsum tau txiav txim siab tias CKD yog ib qho tseem ceeb tshaj plaws rau cov xwm txheej ntawm cov hlab plawv.3 Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb (WHO) tau tshaj tawm cov kab kos los ntsuas qhov kev tuag ntawm cov hlab plawv kaum xyoo tsis suav nrog CKD raws li qhov muaj feem cuam tshuam, thaum CKD tsis tshua muaj txiaj ntsig hauv qhov no ntau dua li suav nrog DM.3,8 Qhov no tuaj yeem ua rau ib qho underestimation ntawm nws lub ntsiab lus.
Overhydration: Ib qho cuam tshuam Mob raum mob inevitably ua rau ntim ntau dhau nyob rau theem siab dua. Nws ua rau muaj ntshav siab, mob hlab ntsha, kev hloov pauv ntawm cov kua dej mus rau qhov chaw thib peb, sab laug ventricular hypertrophy, thiab kev loj hlob ntawm HF.9,10 Volume overload yog ntseeg tias yog qhov feem ntau ntawm kev pheej hmoo tuag hauv CKD.10,11 Hypervolemia. yog ib qho tsis zoo prognostic yam tsis tau tsuas yog rau cov neeg mob nyob rau hauvhloov lub raumkev kho mob tab sis kuj rau cov neeg nyob hauv lub chaw ua si ua ntej dialysis. Nws yog ib qho kev pheej hmoo txaus ntshai rau kev txhim kho ntawm lub plawv tsis ua haujlwm.12
Overhydration: Ib qho ua rauNws tau pom zoo tias kev xa cov ntshav mus rau qhov zoolub raumNws yog ib qho tseem ceeb rau khaws cia lawv cov dej num, tab sis qhov tsim nyog outflow tsis yog qhov tseem ceeb. "Congestiveraum tsis ua haujlwm"13 tuaj yeem yog qhov kev piav qhia zoo ntawm cov kab mob uas tshwm sim hauv cov neeg mob diastolic HF thiab CKD. Nws ntseeg tau tias sodium retention yog ib txwm txuas nrog dej nthuav dav, lub hom phiaj kho mob tseem ceeb, thiab nws nce siab hauv nruab nrab venous (CVP). Association of CVP thiablub raum ua haujlwmKev puas tsuaj thiab kev tuag ntau dua tau piav qhia nyob rau hauv ib txoj kev tshawb fawb uas cov neeg mob plawv tau txais catheterization ntawm lub plawv sab xis.14 Txawm hais tias qee qhov kev tsis txaus ntseeg hauv kev thaiv kev qhib ob qho tib si renin-angiotensin-aldosterone system (RAAS) thiab lub siab xav muaj nyob, qhov yuav tsum tau txo qis CVP. los kho congestion zoo nkaus li yog unquestionable.14 Nyob rau hauv ntev HF, diastolic dysfunction, uas coexists nrog ntxiv sau siab, feem ntau nrog los ntawmraum tsis ua haujlwm(Daim duab 1); qhov diastolic dysfunction kev loj hlob zuj zus mus rau cov neeg tuag tau tshwm sim.15 Lub pathomechanism tseeb tseem tsis tau nkag siab zoo, tab sis qhov kev cuam tshuam ntawm cov hlab ntsha thiab cov hlab ntsha venous congestion, tau piav qhia ua ke ntau ntxiv.lub raumtom qab thauj khoom, zoo li ua lub luag haujlwm tseem ceeb.13 Ib qho yuav tsum nco ntsoov tias qhov kev nthuav tawm ib ntus rau inflammatory mediators, endotoxins lossis hloov lub plab phab ntsa permeability tuaj yeem ua rau muaj qhov cuam tshuam ntxiv (Daim duab 2). Qee zaum, chav kawm tshuaj tua kab mob kom zoo tuaj yeem rhuav tshem cov tshuaj tiv thaiv diuretic los ntawm kev txo qis cov lus teb.
Kev kho mob
Txawm hais tias qhov kev taw qhia ntawm kev sib cuam tshuam ntawm overhydration thiab covlub raum, kev ua kom lub cev qhuav dej yog qhov tseem ceeb. Cov tswv yim kho mob yuav tsum tau kho kom haum vim tias lub qhov rais rau cov kua dej sib npaug hauv cov neeg mob cardiorenal yog nqaim. Qhov kev pom zoo thoob ntiaj teb rau feem ntau ntawm cov neeg mob CKD - kev noj zaub mov tsis muaj sodium xa khoom - yuav tsum yog thawj kauj ruam.16 Nyob rau hauv ntau dua CKD lossis HF exacerbation, xws li kev tswj tsis txaus thiab kev kho tshuaj yuav tsum tau qhia.
Loop diureticsFeem ntau siv cov diuretics hauv HF yog lub voj diuretics, uas ua haujlwm hauv lub voj ntawm Henle; furosemide thiab torsemide yog cov feem ntau ntawm lawv. Qhov kev tsis pom kev, tab sis kuj tsis tuaj yeem tshwm sim ntawm lub voj diuretics yog qhov ua kom muaj zog ntawm lub paj hlwb (SNS) thiab RAAS. Loop diuretics txo qhov congestion tab sis tsis txhob hloov cov neeg tuag thiab rov kho tus nqi nyob rau lub sij hawm luv luv thiab ntev.17 Qhov txo qis ntawm nws cov nyhuv nyob rau hauv lub sij hawm yog ib qho tshwm sim, uas ua rau txo cov sodium thiab chloride tshem tawm; qhov ua rau muaj ntau yam. Pharmacodynamics thiab pharmacokinetics ua lub luag haujlwm tseem ceeb. Loop diuretics yog khi rau cov ntshav cov protein ntau thiab yuav tsum tau tso rau hauv cov tubule ze ze kom ua haujlwm. Lub twj tso kua mis Na / K / 2Cl no nyob rau ntawm luminal sab ntawm nephron. Yog li ntawd, lub voj diuretics yuav tsum ncav cuag cov kua hauv tubular kom ua haujlwm. Li no, hauv cov neeg mob hnyavlub rauminsufficiency (piv txwv li, GFR< 15 ml in),="" larger="" doses="" of loop="" diuretics="" are="" required="" to achieve="" effective="" concentrations.18="" the various="" loop="" diuretics="" differ="" in intestinal="" absorption,="" especially="" with="" an edematous="" bowel="" wall="" present="" in decompensated="" hf.="" reduced="" drug="" excretion="" to the lumen="" of the tubule,="" reduced="" filtered="" load="" of sodium="" and="" increased="" raas="" and="" sns="" activation="" due="" to hf-related="" underfilling="" and="" extracellular="" fluid="" volume="" (ecfv)="" depletion,="" which="" attenuates="" the peak="" effect="" of the diuretic,="" also="" contribute="" to the resistance.19,20="" the vasopressin="" release,="" enhanced="" by angiotensin="" ii="" and="" baroreceptor-mediated="" mechanism="" in more="" advanced="" hf,="" increases="" nephron="" water="" reabsorption.21="" the braking="" phenomenon,="" which="" impairs="" sodium="" loss="" in the course="" of time,="" distal="" tubular="" hypertrophy,="" and="" hypochloremia,="" which="" plays="" a role="" in the activation="" of neurohormonal="" activity,="" can="" also="" contribute="" to diuretic="" resistance.22="" the attempts="" to break="" the resistance="" encompass="" more="" frequent="" dosing,="" sometimes="" multiple="" times="" per="" day,22="" as well="" as adjusting="" the dose="">lub raum ua haujlwm, kev tswj hwm cov tshuaj hauv cov hlab ntsha thiab hloov ntawm furosemide mus rau torsemide lossis bumetanide.16
Kev sib xyaw ntawm cov tshuaj diuretics sib txawv yog lwm kauj ruam los rhuav tshem qhov tsis kam. Thaiv sodium reabsorption nyob rau hauv ntau seem ntawm nephron zoo li yog lub hom phiaj tseem ceeb. Loop diuretics ua los ntawm lumen thiab yog lub luag haujlwm rau inhibition ntawm Na / K / Cl2 cotransporter nyob rau hauv tuab ascending voj ntawm Henle thiab macula densa. Lawv inhibit tus thauj khoom los ntawm kev khi rau hauv lub hnab ntim translocation los ntawm chloride-binding site. Kev siv lub voj diuretics ua rau muaj kev nce siab ntawm sodium nyob rau hauv qhov chaw ntawm lub nephron thiab txhawb nqa sodium reabsorption los ntawm kev siv zog ntawm Na / Cl cotransporter activation, uas yog ib qho ntawm cov txheej txheem tiv thaiv.23 Thiazides thiab thiazide-zoo li tshuaj kuj ua los ntawm lub lumen los ntawm inhibition ntawm Na / Cl cotransporter nyob rau hauv lub distal convoluted tubule, thiab, yog li ntawd, txo sodium reuptake. Txawm hais tias lawv cov txiaj ntsig ua tiav nrog qhov poob hauv eGFR qis dua 30 mL / min / 1.73 m2, kev sib xyaw ntawm lub voj diuretics nrog thiazides rau qee qhov taw tes yog qhov ncaj ncees.
CISTANCHE yuav txhim kho lub raum / raum tsis ua haujlwm
Mineralocorticoid receptor antagonists (MRAs) - spironolactone thiab eplerenone - tau pom tias txhim kho kev mob thiab kev tuag hauv cov neeg mob HF, piv txwv li hauv RALES txoj kev tshawb fawb. Lawv inhibit aldosterone receptors nyob rau hauv lub distal nephron thiab sau raj, txo Na channel thiab Na / K ATPase. Ib tug yuav tsum nco ntsoov tias tag nrho cov diuretics uas lub hom phiaj sau tubules tuaj yeem ua rau hyperkalemia; yog li ntawd, lawv feem ntau tsis siv rau cov neeg mob HF. Qhov no, txawm li cas los xij, tuaj yeem tswj tau los ntawm kev muab lub voj voog diuretic, qhov ncauj bicarbonate (yog tias acidosis tau lees paub) lossis potassium binders hauv plab. Cov koob tshuaj natriuretic yuav tsum ntau dua 25 mg / hnub ntawm spironolactone lossis 50 mg / hnub ntawm eplerenone.
Tolvaptan,ib qho kev xaiv antagonist rau vasopressin receptor V2, tau tshawb xyuas hauv EVEREST sim los ntsuas nws cov txiaj ntsig zoo rau cov neeg mob HF. Nws txo qis dyspnea, edema, lub cev hnyav, thiab qib sodium ntsev, tab sis tsis cuam tshuam tag nrho kev ciaj sia, kev tuag txuas nrog CVD thiab pw hauv tsev kho mob rau HF.24.
Ultrafiltration Thaum lub diuretic teb tsis zoo los yog tsis kam mus rau diuretic therapy tsim thiab lub plawv los yograumInsufficiency deteriorates, ultrafiltration (UF) yog ib qho kev daws teeb meem uas tsim nyog xav txog.25 Hauv kev sib piv rau lub voj diuretics, nws lav decongestion nrog ntau dua sodium poob thiab qis RAAS stimulation.19 Ntau qhov kev sim randomized tau ua los tshawb xyuas cov txiaj ntsig zoo ntawm UF lub tswv yim. RAPID-CHF (Kev Pabcuam rau Cov Neeg Mob Mob Ntshav Qab Zib Uas Tsis Txaus Siab Nrog Decompensated Congestive Heart Failure) thiab UNLOAD (Ultrafiltration vs Intravenous Diuretics rau Cov Neeg Kho Mob Hauv Tsev Kho Mob rau Acute Decompensated Congestive Heart Failure) kev sim tau pom qhov zoo tshaj ntawm UF nyob rau hauv cov kev kho mob 2. ,27 Hauv CUORE (Nruam Ultrafiltration rau Congestive Heart Failure) sim, qhov kev poob phaus tau zoo ib yam hauv ob pawg UF thiab diuretic, tab sis qhov nce hauv cov ntshav creatinine hauv pab pawg kho nrog diuretics thiab qhov tshwm sim me me ntawm HF rehospitalizations hauv HF pawg tau soj ntsuam.28 CARESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) txoj kev tshawb no qhia txog qhov kev poob phaus zoo sib xws hauv UF thiab cov neeg mob diuretic, tab sis kuj tseem ua rau cov ntshav creatinine zuj zus ntxiv thiab muaj kev cuam tshuam ntau dua rau cov neeg mob uas tau UF.29 Tsis tas li ntawd, nyob rau hauv AVOID-HF (Aquapheresis vs Intravenous Diuretics Hospitalizations for Heart Failure) txoj kev kawm, ib qho kev tshwm sim ntau dua nas. io hauv UF cov neeg mob tau hais txog, thaum tsis muaj qhov sib txawv tseem ceeb hauv peb lub hlis kev kho mob ntawm diuretic thiab UF pawg tau pom. Qhov kev sim no raug txiav ua ntej ntxov vim qhov kev tso npe qeeb.30 Sustained low-efficiency dialysis (SLED) yog ua rau cov neeg mob nrog NYHA (New York Heart Association) chav kawm IV nrog cov txiaj ntsig zoo. Txawm hais tias qhov kev daws teeb meem no yuav tsum tau nkag mus rau hauv plawv vascular, nws muaj kev ruaj ntseg zoo dua hemodynamic hauv cov neeg mob hnyav. Ib zaug SLED ib zaug, piv rau cov pa hemodialysis, siv sijhawm ntev dua (6-12 h) thiab siv cov ntshav qis (50-200 mL / min) thiab dialysate (200-400 mL / min) ntws. Cov kua ntim tau muab tshem tawm maj mam dhau lub sijhawm ntev, ua kom cov hemodynamic stability.31,32
Kev lim ntshav peritoneal Cov txiaj ntsig ntawm peritoneal dialysis (PD) hauv kev tswj cov ntim ntau dhau hauv cov neeg mob uas muaj refractory HF thiabraum tsis ua haujlwmyog tsim nyog los ntawm kev tshem tawm sodium ntau dua piv nrog cov tswv yim diuretic ib txwm muaj. Tsis ntev los no, ob tus kws kho mob nephrologists thiab kws kho plawv txaus siab rau qhov kev hloov pauv no hauv CRS.33,34 Rau CRS hom 1, tidal PD tau pom tias muaj kev nyab xeeb thiab siv tau zoo ntawm kev tshem tawm cov co toxins thiab cov dej ntau dhau. Hauv kev tshawb fawb me me, nws zoo dua rau UF txoj kev kho mob thaum khaws cia ntawm lub raum ua haujlwm, txhim kho kev ua haujlwm ntawm lub plawv thiab cov kua dej poob tau raug txiav txim siab.35 Ntxiv mus, tus nqi siab dua ntawm cov xwm txheej tsis zoo tau pom hauv UF caj npab. Ib txoj kev tshawb fawb Brazilian yav tom ntej kuj tau lees paub qhov siab-ntim PD (xws li Kt/V = 0.50/ ntu) raws li muaj txiaj ntsig hauv CRS hom 1 tus neeg mob, tso cai rau kev tswj cov metabolic thiab kua dej txaus.
Hauv HF ntev nrog CKD, thaum eGFR poob qis dua 25 mL / min / 1.73 m2, peritoneal UF tuaj yeem txhim kho kev ua haujlwm txhua hnub thiab txo kev mus pw hauv tsev kho mob. Kev tshuaj xyuas cov txheej txheem npaj los ntawm pab pawg Ronco tau soj ntsuam qhov ua tau zoo ntawm PD hauv cov neeg mob nrog refractory CHF.34 Nees nkaum-ib txoj kev tshawb fawb suav nrog 673 tus neeg mob; Cov kws sau ntawv tau hais tias nyob rau hauv cov neeg mob uas muaj refractory CHF, PD tuaj yeem yog qhov kev kho mob zoo thiab muaj kev nyab xeeb, ua rau lub plawv ua haujlwm tau zoo thiab tswj qhov hnyav dua. Wojtaszek et al. tau pom qhov ua tau zoo ntawm peritoneal UF nrog rau hmo ntuj, 12- teev, 7.5 feem pua icodextrin pauv hauv kev kho mob mus sij hawm ntev ntawm refractory HF nyob rau hauv feem ntau ntawm NYHA chav kawm IV cov neeg mob.36 Ib hmos icodextrin pauv tau tshwm sim los ua ib qho kev xaiv kho tau zoo. raws li ib qho ntxiv rau kev tswj hwm pharmacological. Cov kws sau ntawv tau hais tias kev kho mob tuaj yeem cuam tshuam zoo rau lub neej zoo thiab tag nrho cov nqi kho mob.
CISTANCHE yuav txhim kho lub raum / raum mob ntshav qab zib
Nyob rau hauv xyoo tas los no, ntau dua, cov kev tshawb fawb tau lees paub PD raws li kev kho mob palliative zoo thiab ua tau rau refractory CHF hauv hom 2 CRS.37 Pavo li al. txheeb xyuas ntau yam los txheeb xyuas cov neeg mob uas muaj refractory HF thiab congestive txoj cai ventricular dysfunction uas yuav tau txais txiaj ntsig zoo tshaj plaws los ntawm PD.38 Cov neeg mob uas muaj kev paub ntau dua rov qab tsis ua haujlwm, tsis tshua muaj cim tseg.lub raum ua haujlwmkev puas tsuaj thiab cov uas tsis nyob ntawm lwm tus rau kev pab yog feem ntau yuav tau txais txiaj ntsig los ntawm PD. Hauv cov ntsiab lus, PD yuav tsum tau ua raws li kev txiav txim siab thaum refractoriness rau kev saib xyuas kev kho mob tshwm sim. Cov xwm txheej hauv chaw kho mob, xws li mob plawv txoj cai congestion, ascites nrog intensified diuretic kev kho mob, Ntau tshaj los yog sib npaug rau 2 mus pw hauv tsev kho mob nyob rau hauv 6 lub hlis vim hais tias ntawm lub plawv decompensation txawm tias kev kho mob zoo los yog mob.raum tsis ua haujlwmThaum lub sij hawm muaj kev tiv thaiv kev kho mob ntawm lub plawv decompensations yog cov uas PD yuav tsum tau txiav txim siab.
Cov pab pawg tshwj xeeb ntawm cov neeg mob: Mob ntshav qab zib mellitus mellitus yog feem ntau ua rau CKD nyob rau hauv lub ntiaj teb no thiab yog ib qho kev ywj pheej ntawm kev tuag nyob rau hauv lub chav kawm ntawm CVD.39 Raws li post hoc ACCORD mus soj ntsuam, nyob rau hauv cov neeg mob ntshav qab zib, CKD thiab / los yog CVD ua rau tag nrho cov-ua rau tuag thiab mob plawv. xwm txheej prognosis.40 Yog li ntawd, niaj hnub tshuaj tiv thaiv kab mob ntshav qab zib yuav tsum tsis yog tsuas yog ib tug zoo hypoglycemic nyhuv tab sis kuj nephron- thiab cardioprotective tshwm sim. Vim tias nws cov yam ntxwv muaj txiaj ntsig zoo, xws li tus nqi qis, kev nyab xeeb ntawm kev siv thiab cov txiaj ntsig tau zoo ntawm cov hlab plawv, metformin yog thawj kab tshuaj.41 Nws tsis tas yuav tsum tau tso tseg hauv cov neeg mob CKD, txawm tias eGFR poob qis dua 45. mL / min / 1.73 m2, thiab, raws li kev soj ntsuam tsim nyog, tuaj yeem siv txog li 30 mL / min / 1.73 m2. 39 Txawm li cas los xij, rau cov neeg mob ntau, kev kho mob monotherapy tsis txaus. Muab rau hauv tus account qhov kev pheej hmoo plawv loj heev, cov kev tshawb fawb tau mus rau hauv cov kev taw qhia ntawm kev nrhiav kev daws teeb meem ntau dua pleiotropic. Ob pawg tshuaj yuav tsum tau paub qhov txawv ntawm no: sodium-glucose cotransporter 2 (SGLT2) inhibitors thiab incretin tus neeg sawv cev - glucagon-zoo li pep tide-1 (GLP-1) receptor agonist.42 Cov pab pawg tshuaj kho mob tshiab no txo qis. Kev pheej hmoo tuag plawv, nrog SGLT2 inhibitors (SGLT-2i) cuam tshuam HF kev pheej hmoo, thiab GLP-1RAs txo MI kev pheej hmoo.42
Sodium-glucose co-transporter -2 inhibitors Qhov kev sim EMPA-REG OUTCOME yog ib qho kev tshawb fawb tsom rau kev ntsuam xyuas cov kab mob plawv. Cov kws tshawb fawb randomized tshaj 7020 hom 2 DM (T2DM) cov neeg mob uas muaj kev pheej hmoo siab plawv thiab tshuaj xyuas qhov cuam tshuam ntawm empagliflozin. Thaum txoj kev tshawb no, cov txiaj ntsig tseem ceeb, xws li kev tuag los ntawm cov hlab plawv, tsis tuag MI lossis tsis mob stroke, thiab tag nrho cov neeg mob tuag tau txais kev sib txawv ntawm koob tshuaj empagliflozin (tus SGLT2 inhibitor) thiab placebo, raug soj ntsuam. Nws tau txiav txim siab tias kev tswj hwm ntawm SGLT2i, uas ua haujlwm nyob rau hauv cov tubule ze ze los ntawm kev nce glucosuria, hauv 2 koob tshuaj, 10 mg thiab 25 mg, txo qis qhov kawg ntawm cov ntsiab lus nyuaj (los ntawm 14 feem pua thiab 32 feem pua, raws li) piv rau cov placebo. Lub tswv yim tseeb ntawm kev ua tsis tau nkag siab zoo, tab sis qhov kev tiv thaiv ntawm cov tshuaj yog tej zaum nyob rau hauv cov kev hloov nyob rau hauv lipid theem thiab txo nyob rau hauv cov nram qab no: sympathetic kev ua si, ntshav siab, albuminuria, uric acid tuav, oxidative kev nyuaj siab, thiab insulin kuj. 43,44 ib
Kev qeeb qeeb ntawm kev nce qib ntawm CKD yog qhov tshwm sim ntxiv ntawm empagliflozin. Cov neeg mob CKD nyob rau theem G1-3b tau raug soj ntsuam rau eGFR thaum lub sijhawm sim thiab nws tau pom tias tom qab thawj zaug kev poob qis hauv eGFR hauv thawj 4 lub lis piam ntawm kev soj ntsuam, kev loj hlob ntawm tus kab mob tau ruaj khov hauv cov neeg mob tau txais empagliflozin, thaum eGFR poob qis dhau sijhawm hauv pab pawg tau txais cov placebo.45 Cov eGFR txoj kab nqes tsom los ntawm EMPA-REG OUTCOME sim ntsuas GFR qhov sib txawv hauv 3 lub sijhawm sib txawv, uas yog, tsis ntev tom qab pib ntawm txoj kev kho, thaum lub sijhawm kho mob ntev, thiab tom qab noj tshuaj. Lawv cov kev soj ntsuam - eGFR tus txheeb ze poob qis hauv theem 1, inhibition ntawm eGFR poob hauv lub sijhawm thib 2, thiab thaum kawg eGFR nce nyob rau theem kawg tom qab kev siv tshuaj - txhawb qhov kev xav tias muaj cov nyhuv renoprotective ntawm empagliflozin, txo qis hauv intraglomerular siab. los ntawm cov tshuaj thiab cov nyhuv SGLT2i ntawm hemodynamic hloov thiab nws reversibility.46
EMPEROR Txo qis [ejection feem] kev sim tshuaj ntsuam xyuas cov txiaj ntsig ntawm empagliflozin ntawm HF, tsis hais txog qhov mob ntshav qab zib, rau cov neeg mob uas muaj feem ejection ntawm 40 feem pua thiab tsawg dua. Hauv qhov kev sim no, 3730 tus neeg mob nrog NYHA chav kawm II-IV HF tau muab faib ua 2 pawg - placebo thiab 10 mg empagliflozin ib hnub ib zaug. Nws tau muab tawm tias cov neeg mob tau txais empagliflozin muaj qhov pheej hmoo tsawg dua ntawm kev ua tau zoo, xws li kev tuag ntawm lub plawv lossis kev mus pw hauv tsev kho mob rau HF, dua li cov neeg mob tau txais cov placebo (19.4 feem pua piv rau 24.7 feem pua). Txoj kev tshawb no qhia tsis tau tsuas yog ib tug zoo plawv, tab sis kuj covlub raum nyhuvCov tshuaj empagliflozin. Cov txiaj ntsig thib ob, tus nqi ntawm qhov poob qis hauv eGFR nyob rau lub sijhawm ntawm kev kho mob, qeeb qeeb hauv pawg empagliflozin dua li hauv pawg placebo (−0.55 mL / min / 1.73 m2 piv rau −2.28). mL / min / 1.73 m2). Tsis tas li ntawd, qhov tshwm sim ntawm lub raum sib xyaw ua ke, uas yog, qhov pib ntawm kev kho lub raum hloov pauv (kev lim ntshav ntev lossis hloov lub raum) lossis kev txo qis hauv eGFR tshwm sim hauv cov neeg mob tsawg dua hauv empagliflozin dua li hauv pawg placebo (1.6 feem pua piv rau 3.1. feem pua). Nws yog ib qho tsim nyog hais tias 48 feem pua ntawm cov neeg mob cuv npe muaj eGFR tsawg dua 60 mL / min / 1.73 m2. 47
Cov nyhuv ntawm empagliflozin rau cov neeg mob nrog HF nrog khaws cia ejection feem tseem raug kawm nyob rau hauv ib qho kev tsim zoo sib xws EMPEROR Preserved [ejection fraction] mus sib hais. Empagliflozin muaj txiaj ntsig zoo rau cov neeg mob CKD vim tias nws cuam tshuam rau kev tswj cov kua dej. Qhov no yog qhov tseem ceeb, vim tias CRS feem ntau ua ke nrog dej ntau dhau. Qhov kev cuam tshuam zoo ntawm empagliflozin ntawm HF nrog ob qho tib si khaws cia thiab txo qis ejection feem (HFpEF thiab HFrEF) thiab kub siab yog piav qhia los ntawm natriuresis enhancement.48 Qhov kev tiv thaiv rau lub cev natriuretic peptide thiab cov tshuaj diuretics hauv HF yog ntau; sodium-hydrogen antiporter 3 los yog, ua lwm yam lus, sodium-hydrogen exchanger (NHE 3), nyob rau hauv proximallub raumtubule, uas nws ua kom nce hauv HF, yog qhov xav tias yog tus neeg ua txhaum.49 NHE3 cov protein, uas koom nrog SGLT2,50 yog lub luag haujlwm rau feem ntau ntawm sodium reuptake hauv cov tubules. SGLT2i cuam tshuam nrog NHE3 los ntawm nws qhov inhibition thiab ua rau natriuresis. Kev tswj hwm tib lub sijhawm ntawm lub voj diuretics tuaj yeem tiv thaiv qhov nce ntxiv ntawm sodium reuptake nyob rau hauv ntau qhov chaw ntawm nephron.51 Lwm qhov kev npaj rau kev ua tau zoo ntawm empagliflozin yog qhov kev xav ntawmlub raumcongestion thiab SGLT2i tuav taw tes tsom rau dej intracellular. Vim yog lub zos SGLT2i-induced hypovolemia nyob rau hauv lubraum,cov kua dej interstitial kis tau yooj yim mus rau qhov chaw vascular kom them rau cov kua dej poob. Vim qhov kev xav no, lub ntim ntim, thiab yog li, lub cev perfusion thiab arterial txhaws, yuav tsis cuam tshuam. Tsis tas li ntawd, lub interstitiallub raumntim overload txo qis thiab tiv thaiv lub raum ua haujlwm.52
Lwm yam gliflozin tsim nyog hais yog dapagliflozin. DECLARE-TIMI 58 (Tshem Tawm ntawm Dapagliflozin ntawm Qhov tshwm sim ntawm Cov Kab Mob Ntshav Qab Zib - Thrombolysis hauv Myocardial Infarction 58) kev sim tau tsim los txheeb xyuas cov ntaub ntawv dapagliflozin cardiovascular kev nyab xeeb. Hauv qhov kev sim no, 17,160 T2DM cov neeg mob tau muab faib ua pawg tau txais cov tshuaj lossis cov placebo. Kev kho mob Dapagliflozin txo qis tus nqi ntawm HF mus pw hauv tsev kho mob thiab cov hlab plawv tuag tab sis tsis cuam tshuam cov xwm txheej tseem ceeb hauv plawv plawv (MACE), txhais tau tias yog mob plawv tuag, MI lossis ischemic stroke, hauv pab pawg neeg mob uas muaj thawj atherosclerotic CVD lossis muaj kev pheej hmoo ntawm ib.53 Kev cog lus. Cov txiaj ntsig tau pom nyob rau hauv Dapagliflozin thiab Kev Tiv Thaiv Kev Tsis Txaus Siab tshwm sim hauv ChronicKab mob raum(DAPA-CKD) theem III kev sim, tsom rau thawjlub raumqhov tshwm sim. Hauv kev sim DAPA-CKD, qhov kawg ntawm qhov sib xyaw ua ke (Ntau dua lossis sib npaug li 50 feem pua ntawm kev poob qis hauv eGFR, qhov pib ntawm ESKD, lossis mob plawv lossis lub raum tuag) hauv ib pawg ntawm cov neeg mob CKD nrog eGRF ntawm 25–75 mL / min / 1.73 m2 nrog thiab tsis muaj DM tau raug soj ntsuam.54 Thaum kawg ntawm lub Peb Hlis 2020, qhov kev sim tau raug txiav ntxov ntxov vim qhov ua tau zoo ntawm cov neeg mob lub raum tsis txaus. Ib yam li tsim qauv EMPA-Kidney sim ua, tab sis cov txiaj ntsig peb yuav muaj nyob rau xyoo 2022.
Lwm yam SGLT2i kuj raug soj ntsuam hauv kev sim. Kev tsom mus rau cov txiaj ntsig ntawm cov hlab plawv, CANVAS (Canagliflozin Cardiovascular Assessment Study) qhov kev kawm suav nrog 2 qhov kev sim ntawm 10,142 T2DM cov neeg mob uas muaj kev pheej hmoo siab CVD. Nws tau tsim los ntsuas cov txiaj ntsig ntawm canagliflozin-kev pheej hmoo. Qhov kev zov me nyuam tau pom qhov zoo tshaj ntawm SGLT2i dhau ntawm pawg placebo hauv kev txo qis hauv cov hlab plawv, tab sis cov kev cuam tshuam tsis zoo - kev txiav tawm ntawm cov ntiv taw lossis metatarsal - ntau zaus hauv pawg canagliflozin.55 CREDENCE (Canagliflozin thiabLub raumEndpoints nyob rau hauv Diabetes nrog tsim nephropathy Clinical Evaluation) txoj kev tshawb no yog tsom rau canagliflozin thawj lub raum tshwm sim. Cov neeg mob suav nrog eGFR ntawm 30–90 mL/min/1.73 m2 thiab kwv yees proteinuria txhua hnub ntawm qib 0.3-5 g. Kev tshawb fawb pom tias ob qho tib siraum tsis ua haujlwmthiab qhov kev pheej hmoo ntawm cov kab mob plawv tau qis dua hauv pab pawg tau txais canagliflozin piv rau pawg placebo. Txoj kev tshawb no tau tso tseg tom qab kev soj ntsuam ib ntus, raws li qhov ua tau zoo ntawm kev ua tau zoo tau txais tom qab randomizing 4401 cov neeg mob.56 Cov ntsiab lus ntawm SGLT2i tau hais los saum toj no yog raws li hauv qab no: empagliflozin, canagliflozin, thiab dapagliflozin tau sau tsis ntev los no hauv kev tshuaj ntsuam meta. Nws tau txiav txim siab tias SGLT2i txo HF mus pw hauv tsev kho mob, uas cov pov thawj yog qhov muaj zog tshaj, MACE thiab tag nrho cov neeg tuag. Cov pov thawj tsis muaj zog nyob rau hauv pab pawg neeg mob nrog eGFR< 60 ml in/1.73 m2;="" yet,="" the impact="" on lowering="" adverse="" renal="" effects="" is observable="" even="" in this="" group="">
Ntawm cov yam ntxwv xav tau ntawm SGLT2i, kev poob phaus, ntshav siab-txo, cov nyhuv uricosuric, thiab tsis muaj kev pheej hmoo ntawm hypoglycemia yog tsim nyog hais. Gliflozins txo qis hyperfiltration nyob rau theem pib ntawm mob ntshav qab zib nephropathy, raws li lawv rov qab cov lus qhia tubuloglomerular (TGF).58 CVD-REAL3 yog ib qho kev tshawb fawb soj ntsuam los ntsuas SGLT-2i cuam tshuam raulub raum ua haujlwmHauv kev sib piv rau lwm cov tshuaj txo cov piam thaj hauv lub ntiaj teb kev kho mob tiag tiag. Nws tau xaus lus tias qhov pib ntawm kev kho nrog SGLT2i, uas yog: dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, thiab luseogliflozin, yog txuam nrog kev pheej hmoo tsawg dua ntawm qhov loj.raumxwm txheej thiab ib tug qeeb qeeb hauvlub raum ua haujlwmtshaj li qhov pib ntawm lwm yam tshuaj tiv thaiv kab mob ntshav qab zib.59 Cov lus pom zoo ntawm American Diabetes Association qhia tias kev kho thib ob DM yuav tsum raug xaiv los ntawm lub hauv paus ntawm lub neej ntawm atherosclerotic CVD (ASCVD), HF lossis CKD comorbidity. Lub plawv tsis ua hauj lwm lossis CKD predominance txhais tau hais tias siv SGLT2i los txo CKD kev nce qib thiab / lossis HF, thaum ASCVD predominance qhia SGLT2i lossis GLP-1 receptor agonist siv nrog xav tias muaj txiaj ntsig plawv.60,61
Incretin tshuaj Glucagon-zoo li peptide-1 (GLP-1) receptor agonists yog lwm cov tshuaj tiv thaiv hyperglycemic uas nthuav tawm cov khoom nephroprotective, vim lawv tiv thaiv qhov tshwm sim ntawm myoglobinuria thiab qhov tsis zoo hauvlub raum ua haujlwm.62 Lub putative renoprotective effect ntawm GLP-1 receptor agonists yog ncaj qha thiab tsis ncaj (dichotomic). Cov kev ua tsis ncaj muaj xws li, ntawm lwm tus, ntawm kev tswj glycemic thiab ntshav siab, kev poob phaus, thiab txhim kho cov hlab ntsha thiab sab laug ventricular phab ntsa. Cov kev cuam tshuam ncaj qha suav nrog kev txo qis hauv lub raum thiab cov kab mob hauv lub cev, txo cov kev ntxhov siab oxidative, txo qis ntawm lub raum hypoxia, thiab sodium thiab dej modulation.63 Natriuresis zoo li yog lub ntsiab ntawm kev txo qis dej ntau dhau. Nws tau pom zoo tias cov nyhuv natriuretic ntawm GLP-1 feem ntau cuam tshuam nrog kev cuam tshuam ntawm NHE3 kev ua haujlwm hauv txhuam ciam teb ntawm lub raum proximal tubule.64 Lwm tus kws sau ntawv, uas tau kawm txog qhov cuam tshuam ntawm GLP-1 agonists ntawm kev noj qab haus huv saline- loaded txiv neej, hais tias cov nyhuv natriuretic yog induced los ntawm ib tug tubular mechanism nyob rau hauv distal nephron ntu. Cov txheej txheem no ntseeg tau tias yog qhov thib ob rau kev tawm tsam ntawm angiotensin II (ANG II) thiab ywj siab ntawm lub raum hemodynamics. Xws li kev xav txog kev ua haujlwm txhawb nqa lub neej ntawm GLP-1-lub raum axis.65 Kev txhim kho tubuloglomerular tawm tswv yim thiab ameliorating glomerular hyperfiltration hauv cov neeg mob uas muaj T2DM kuj tseem xav tau.64
Hauv kev coj ua (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) sim, 9340 cov neeg mob ntshav qab zib tau randomized. Lub sij hawm-rau-kev tshwm sim ntawm kev tuag los ntawm cov hlab plawv ua rau, nonfatal MI lossis nonfatal stroke raug soj ntsuam. Cov txiaj ntsig tau pom tias lub sijhawm rau qhov tshwm sim thawj zaug yog luv dua hauv liraglutide dua li hauv pawg placebo.66 Tseem muaj lwm qhov kev sim ntsuas GLP-1 agonists, zoo li ELIXA67 nrog lixisenatide, SUSTAIN-668 nrog semaglutide, AWARD-769 nrog dulaglutide, EXCEL70 nrog exenatide, thiab LIRA-RENAL71 dua nrog liraglutide. Txawm hais tias muaj pov thawj rau GLT-1 agonists kom txo qis albuminuria, cov pov thawj rau lub raum nyuaj kawg tseem yuav pom.62 Kuj ceeb tias, piv rau SGLT2, tsis muaj GLP-1 receptors hauv lub raum tubule. los yog lwm yamraumchav tsev.
Cov ntsiab lus
Cov kab mob plawv uas ua rau HF yog ib qho teeb meem CKD, tab sis lub plawv tsis txaus kuj tuaj yeem ua raulub raum ua haujlwmkev puas tsuaj. Cardiorenal syndromes muaj cov tsos mob tshwm sim: overhydration. Vim tias lub hom phiaj kho tsis yog ib txwm ua tiav los ntawm kev siv lub voj voog diuretics vim tsis muaj zog, lwm txoj kev tswj cov kua dej ntau dhau yuav tsum tau ua. Ultrafiltration txo cov tsos mob zoo, tab sis tsis muaj pov thawj tias nws txhim kho txoj sia nyob mus ntev. Peritoneal dialysis zoo li ib qho kev daws teeb meem zoo nkauj hauv refractory CRS hom 2 thiab hauv cov neeg mob xaiv hauv CRS hom 1 kho. Tolvaptan tau ua kom txo qis cov tsos mob tab sis tsis ua pov thawj los cuam tshuam cov ntsiab lus nyuaj. Ib qho kev xaiv kho mob nthuav tawm tshwm sim rau cov neeg mob ntshav qab zib thiab cov neeg mob uas tsis yog mob ntshav qab zib nrog CRS. SGLT2i yog qhov tseem ceeb tshwj xeeb, uas qhia txog cov teebmeem ntawm lub plawv thiab cov hlab plawv, piv txwv li, los ntawm kev txo qis dej ntau dhau (tsuas yog los ntawm NHE3 inhibition). Liraglutide, GLP-1 receptor agonist, tej zaum yuav qhia txog NHE3 inhibition nyhuv nrog SGLT2i thiab tseem muaj cov khoom siv cardio- thiab renoprotective. Txawm hais tias cov neeg ua haujlwm tshiab zoo li tau cog lus rau cov neeg mob overhydrated nrog CRS, cov kev tshawb fawb ntxiv yuav tsum tau ua kom zoo ntsuas lawv lub peev xwm. Txog niaj hnub no, kev tswj hwm cov neeg mob CKD nrog HF thiab cov kua dej ntau dhau tseem nyuaj.
