Ntu 1: Kev Kho Mob Lub plawv tsis ua hauj lwm hauv cov neeg mob uas muaj kab mob raum tsis zoo: Kev tsis ntseeg thiab kev txhim kho tshiab los ntawm ESC Cov Lus Qhia Kawg

Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com

Abstract: Cov neeg mob nrogplawv tsis ua hauj lwm(HF) thiab txuasmob raum mob(CKD) yog cov pej xeem tsawg dua nyob rau hauv kev sim tshuaj; Tsis tas li ntawd, cov neeg uas muaj kev kwv yees hnyav duaglomerular pom tus nqiKev txo qis feem ntau tsis suav nrog cov kev tshawb fawb loj. Hauv qhov teeb meem no, feem ntau ntawm cov ntaub ntawv yog los ntawm kev soj ntsuam tom qab hoc thiab kev tshawb fawb rov qab. Raws li, hauv cov neeg mob uas muaj CKD siab heev, tsis muaj kev tshawb fawb tshwj xeeb uas ntsuas qhov cuam tshuam ntev ntawm cov tshuaj ib txwm siv hauv HF. Cov kev txhawj xeeb tam sim no tuaj yeem cuam tshuam rau txoj hauv kev rau kev kho ib txwm muaj, thiab hauv qhov chaw no, cov kws kho mob feem ntau tsis kam tswj hwm thiab titrate qee tus neeg ua haujlwm ntawm renin-angiotensin-aldosterone system thiab kev ua siab ntev. Yog li, daim ntawv thov dav dav hauv ntau hom HF subtypes nrog rau cov xwm txheej dav dav thiab ntau lub raum tsis ua haujlwm etiologies tseem yog ib qho kev sib cav. Lub luag haujlwm ntawm cov tshuaj tshiab, xws li angiotensin receptor blocker neprilysin inhibitors thiab sodium-glucose linked transporters 2 inhibitors zoo li muab qhov kev xav tshiab rau cov neeg mob CKD. Vim nws txoj kev tiv thaiv vascular thiab hormonal ua, kev siv cov tshuaj no tuaj yeem ua rau muaj kev nyab xeeb rau cov neeg mob.lub raum tsis ua haujlwmnyob rau hauv lub sij hawm ntev. Hauv qhov kev tshuaj xyuas no, peb tau tham txog qhov kev sim loj tshaj plaws uas qhia txog cov ntaub ntawv nrog HF thiab cuam tshuam nrog CKD, thaum qhia txog cov txheej txheem ua haujlwm zoo kom tsis txhob muaj mob raum thiab mob plawv.

Ntsiab lus: plawv tsis ua hauj lwm; mob raum mob; kwv yees glomerular pom tus nqi; sodium-glucose txuas transporters 2 inhibitors; kev kho mob; angiotensin receptor blocker neprilysin inhibitors

Nyem qhov no kom paub txog cistanche kev muag khoom

1. Taw qhia

Cov txheej txheem HF tsis ntev los no tau tshaj tawm cov txheej txheem kho dua tshiab rau kev kho mob plawv tsis ua haujlwm nrog txo qis ejection feem (HFrEF), nrog rau "quadruple therapy" mus kom ze nrog kev siv SGLT-2 inhibitors, angiotensin receptor blocker neprilysin inhibitors (ARN) (raws li kev hloov ntawm angiotensin-hloov enzyme inhibitors (ACE-I) thiab angiotensin receptor blockers (ARBs) lossis hauv cov neeg mob de novo HFrEF nrog cov chav kawm pom zoo llb), nyob rau sab saum toj ntawm B-blockers, thiab mineralocorticoid receptor antagonists (MRAs) , nrog rau kev txhim kho loj heev hauv kev kho mob cov txiaj ntsig ntawm kev mus pw hauv tsev kho mob thiab kev tuag[1]. Txawm li cas los xij, renin-angiotensin system (RAAS) inhibitors, MRAs, angiotensin receptor blocker neprilysin inhibitors (ARNI), thiab sodium-glucose linked transporters 2 (SGLT2) inhibitors cuam tshuam rau lub raum ua haujlwm vim kev hloov hauv lub raum physiology. Cov tshuaj no rov pib dualub raum ua haujlwmnkhaus, cuam tshuam rau intraglomerular hydrostatic pressures-natriuresis kev sib raug zoo los ntawm tubule-glomerular tawm tswv yim mechanism thiab los ntawm kev sib piv cov teebmeem ntawm afferent thiab efferent glomerular arteriola ntxias los ntawm cov neeg ua haujlwm sib txawv. Cov teebmeem no hloov pauv qhov physiological filtration feem, muaj qhov sib txawv preceptorial thiab chemotactic repercussions ntawm macula densa thiab tej zaum yuav cuam tshuam rau tubular muaj nuj nqi (Daim duab 1). Kev sib xyaw ua ke ntawm RAAS inhibitors, MRAs, thiab cov tshuaj tshiab xws li SGLT2 inhibitors thiab ARNI tuaj yeem ua kom cov txheej txheem ntawm lub raum tsis zoo tshwm sim tom qab kev tswj hwm thaum ntxov, uas ua rau muaj kev tsis txaus ntseeg ntawm qhov pib thiab nce-titration ntawm cov kev kho mob cawm siav. Feem ntau, lub raum tsis zoo yog qhov hloov pauv, thiab lub raum ua haujlwm zoo li rov qab mus rau nws cov xwm txheej ua ntej lossis nyob ruaj khov rau lub sijhawm ntev [2]. Txawm li cas los xij, qhov cuam tshuam ntawm lub raum ua haujlwm raug ntxias los ntawm polytherapy tsis raug soj ntsuam txaus. Yog li, HF cov neeg mob uas muaj lub raum tsis ua haujlwm tsis zoo yuav tsis tshua tau txais cov kev qhia pom zoo, txawm tias qhov no tsis yog ib txwm muaj tseeb. Hauv kev tshuaj xyuas no, peb tau tshaj tawm cov teebmeem ntawm lub raum ntawm lub plawv tsis ua haujlwm (HF) cov tshuaj hauv cov neeg mob uas muaj HF thiab mob raum mob (CKD), thiab peb tau qhia txog kev siv cov kev pabcuam cawm txoj sia no hauv kev kho mob.

2. Cov yam ntxwv kho mob ntawm cov neeg mob uas muaj kab mob raum thiab mob plawv

Cov kev tshawb fawb yav dhau los ntawm cov neeg mob sab nraud uas muaj HF ntev tau pom tias ib qho ntawm qhov muaj ntau tshaj plaws ntawm cov kab mob uas tsis yog hlab plawv muaj feem cuam tshuam rau lub raum tsis ua haujlwm li ntawm 30 feem pua ​​​​rau 50 feem pua ​​[3]. Lub plawv thiab ob lub raum tau nruj me ntsis cuam tshuam; kev ua haujlwm tsis zoo ntawm ob qho tib si ntawm lub cev ua rau kev ua haujlwm tsis zoo ntawm lwm yam vim muaj ntau yam txheej txheem, xws li o, oxidative stress, impaired hydro-saline homeostasis, thiab diuretic resistance [4,5]. Hauv HF ntev, muaj qhov txo qis hauv plawv, feem ntau vim HFrEF ua rau txo qis hauv lub cev perfusion. Hauv cov neeg mob uas muaj HFpEF, qhov siab siab siab yog lub ntsiab hemodynamic feature, thiab txo qis systolic filling ua rau tsis txaus stroke ntim tseg, thaum kawg ua rau lub plawv tsis zoo. Kev txo qis ntawm cov hlab plawv hauv cov neeg mob uas muaj HF ntev tau pom tias ua rau txo qis hauv lub raum cov ntshav. Tsis tas li ntawd, hauv kev teb rau qhov txo qis ntawm lub plawv, lub raum txhawb nqa cov txheej txheem uas ua rau dej thiab sodium tuav, thaum kawg ua rau subclinical congestion, uas ua rau lub raum tsis ua haujlwm ntxiv. Ob qho tib si hauv qhov chaw sim thiab hauv cov neeg mob uas muaj mob ntev lossis mob HF, qhov nce hauv nruab nrab venous siab lossis plab siab tau cuam tshuam nrog kev pheej hmoo ntawm lub raum ua haujlwm tsis zoo. Hauv cardiorenal syndrome hom 2, CKD tau pom nyob rau hauv 45 txog 63 feem pua ​​​​ntawm cov neeg mob. Lub raum congestion, hypoperfusion, thiab nce txoj cai atrial siab sawv cev rau cov cim ntawm qhov kev kho mob no [6]. Cov neeg mob HF thiab CKD tau koom nrog kev ua neej tsis zoo thiab pom tias muaj kev pheej hmoo siab ntawm cov hlab plawv (CV) vim muaj ntau yam kev pheej hmoo, xws li ntshav qab zib, kub siab, thiab kab mob plawv (CAD)[7]. Phenotyping cov neeg mob uas lub raum tsis ua haujlwm tseem yog qhov nyuaj tiag tiag; Cov txheej txheem pathophysiological thiab lub luag haujlwm prognostic ntawm lub raum tsis ua haujlwm yuav txawv ntawm HFrEE, HFmrEF, thiab HFpEF. CKD feem ntau cuam tshuam nrog HF hnyav dua thiab theem, ntawm nws tus kheej ntawm sab laug ventricular ejection feem (LVEF). Kev sib raug zoo ntawm CKD, hnub nyoog laus, poj niam poj niam txiv neej, ntshav qab zib mellitus, thiab HF theem tau zoo sib xws hauv peb pawg HF, tab sis ntau qhov kev tshawb fawb pom tau tias CKD muaj ntau dua hauv plawv tsis ua hauj lwm nrog khaws cia ejection feem (HFpEF) dua li hauv plawv tsis ua hauj lwm nrog me ntsis txo. ejection feem (HFmrEF) thiab HFrEF [8,9]. Lwm cov kev tshawb fawb pom tias muaj ntau dua ntawm CKD hauv cov neeg mob HFrEF [10]. Kev sib koom ua ke ntawm HFpEF thiab qhov tsis zoo ntawm lub raum ua haujlwm tsis muaj kev ywj pheej ntawm kev muaj CKD ntawm lub hauv paus. Lub raum tsis ua haujlwm hauv HFpEF tej zaum yuav suav hais tias yog qhov mob hnyav, nrog rau kev cuam tshuam dav dav yam tsis muaj kev cuam tshuam rau HF cov xwm txheej tsis zoo: hloov pauv, hauv cov neeg mob HFrEF, lub raum tsis ua haujlwm yuav cuam tshuam txog kev nce qib ntawm HF, tej zaum vim yog lub plawv tsis zoo, hemodynamic hypoperfusion, thiab Kev sib haum xeeb thiab neurohormonal ua kom [11]

Ntawm qhov tsis yog-CV comorbidities, CKD yog tus kab mob ntau dua nrog kev mus pw hauv tsev kho mob[12]. Lub raum tsis ua haujlwm, txawm hais tias nws txhais li cas thiab kev tshuaj ntsuam xyuas, tau muab ib qho kev pheej hmoo tseem ceeb rau kev tuag hauv cov neeg mob HF[13]. CKD tau cuam tshuam nrog cov txiaj ntsig tsis zoo hauv txhua HF phenotypes; Txawm li cas los xij, cov ntaub ntawv hais txog kev tuag hauv HFpEF thiab CKD qhia txog qhov tsis sib haum xeeb. Nyob rau hauv cov kev ntsuam xyuas loj dua, uas suav nrog cov neeg mob HFpEF, CKD yog qhov muaj zog tshaj qhov kwv yees ntawm kev tuag [14]. Conversely, ib tug meta-kev soj ntsuam ntawm lub ntiaj teb no pab pawg neeg nyob rau hauv Chronic Heart Failure (MAGGIC) qhia tau hais tias ib tug tsawg tuag tus nqi thiab ib tug qis dua kev koom tes ntawm CKD thiab tuag nyob rau hauv cov neeg mob nrog HFpEF dua li cov neeg uas muaj HFrEF [15]. Qhov txiaj ntsig no tau lees paub hauv Swedish Heart Failure sau npe, nyob rau hauv uas kev koom tes ntawm CKD thiab kev pheej hmoo tuag tsis tau hais tawm hauv cov neeg mob HFpEF [16].

Hauv cov neeg mob uas mob plawv tsis ua hauj lwm (AHF), peb tuaj yeem pom ob yam phenotypes: cov neeg mob uas muaj lub raum tsis ua haujlwm, txhais tau tias yog CKD, thiab cov neeg mob ua rau lub raum tsis zoo (WRF) thaum mus pw hauv tsev kho mob [17]. Ib qho kev faib tawm tshiab ntawm WRF tau raug npaj, raws li lub sijhawm daws teeb meem lossis kev pheej hmoo. Thawj qhov chaw kho mob yog tus neeg mob uas lub raum ua haujlwm zoo thiab qhov tshwm sim ntawm "pseudo" WRF thaum mus pw hauv tsev kho mob rau mob HF, uas tau suav tias yog theem nrab ntawm kev kho mob decongestion. Kev nce hauv tsev kho mob creatinine feem ntau tsis tshwm sim tom qab tso tawm, yam tsis muaj qhov tshwm sim rau qhov kev tshwm sim yog tias tus neeg mob tau kho zoo, nrog kev ua haujlwm zoo ntawm qhov tso tawm. Qhov thib ob qhov xwm txheej yog tus neeg mob uas muaj WRF tiag tiag vim yog qhov mob hnyav (nce lub raum venous siab) thiab hypoperfusion (txo cov hlab ntsha perfusion), uas lub raum tsis zoo, nrog rau kev nce hauv creatinine hauv lub sijhawm tom qab tso tawm thiab muaj lub nra hnyav dua. HF rov tsev kho mob [18]. Thaum kawg, nyob rau hauv qhov thib peb scenario, WRF tuaj yeem tshwm sim nyob rau hauv lub xub ntiag ntawm CKD cuam tshuam nrog txo cov ntshav cortical thiab mob glomerulosclerosis nrog cov phab ntsa cortical txo. Cov subtype no muaj nyob rau hauv cov neeg laus uas muaj ntau yam comorbidities, qhov twg WRF tau xav txog qhov tsis zoo ntawm lub raum kev ua haujlwm, nrog rau cov txiaj ntsig tsis zoo. Qhov kev faib tawm tam sim no tsis tiav vim nws tsis suav nrog kev ntsuas lub raum tom qab tso tawm thiab qhov hnyav ntawm kev kwv yees zoo glomerular filtration rate (eGFR) kev puas tsuaj (Table 1).

3. Kev Kho Mob Lub Hom Phiaj thiab Kev txwv rau cov neeg mob plawv tsis ua haujlwm thiab mob raum mob

Txhua cov tshuaj siv hauv cov neeg mob HF muaj feem cuam tshuam rau lub raum kev ua haujlwm, thiab lawv nthuav tawm cov neeg mob HF nrog lub raum tsis ua haujlwm kom muaj kev pheej hmoo ntau dua ntawm lub raum tsis zoo, xws li hyperkalemia thiab lim ntshav. Keeb kwm, cov ntaub ntawv los ntawm randomized tswj kev sim ntawm cov tshuaj HF hauv cov neeg mob HF thiab CKD raug txwv, vim tsis suav nrog cov neeg mob CKD.

Cov kev tshawb fawb ntawm sab laug ventricular dysfunction (SOLVD) sim cuv npe kawm 36 feem pua ​​​​ntawm cov neeg mob CKD thiab eGFR<60 ml/min/1.73="" m;33%="" of="" all="" patients="" presented="" a="">0.5 mg/dL increase in serum creatinine; in the final analyses, the benefits on all-cause mortality were maintained across the entire CKDspectrum [19]. This finding was confirmed by the survival and ventricular enlargement (SAVE) trial, which demonstrated the improvement in survival and reduced morbidity in patients with asymptomatic left ventricular dysfunction treated with captopril vs. placebo regardless of CKD(exclusion criteria Cr>2.5 mg/dL,33%of patients with CKD). After 42 months of follow-up, the risk for death associated with renal events was a hazard ratio (HR) of 1.63 (95%CI 1.05-2.52)in the placebo group, versus HR of 1.33 (95% CI 0.81-2.21) in the captopril group (p=0.49 for interaction)[20]. Similar findings were found in the trandolapril cardiac evaluation (TRACE)study group, in which 40% of patients with post-myocardial infarct LV dysfunction had CKD. In this group, trandolapril significantly reduced the risk of CV mortality and HF progression [21]. More recently, in the NETWORK and ATLAS trials, patients with Cr>2.3 mg/dL and Cr>2.5 mg/dL were excluded, and no specific therapeutic data on advanced CKD could be extrapolated. The valsartan heart failure trial (Val-HeFT) included a higher percentage of patients with HF and CKD (58% of the entire cohort); valsartan significantly reduced the combined endpoint of mortality and morbidity and improved HF symptoms also in HF patients with CKD[22]. Notably, candesartan in heart failure assessment of reduction in mortality and morbidity (CHARM)-added and CHARM-alternative trials, which included a significant proportion of the CKD population, confirmed the previous data. However, patients with more severe CKD (creatinine>3.0 mg/dL) tsis suav nrog. Hauv qhov kev tshawb fawb no, feem pua ​​​​ntawm cov neeg mob tseem ceeb (7.1 feem pua) tau txiav tawm txoj kev kho mob vim qhov nce ntawm creatinine, thaum tsis muaj cov ntaub ntawv txaus hais txog qhov cuam tshuam mus tas li ntawm lub raum tshwm sim [23].

Cov qauv Cox proportional hazards regression model nyob rau hauv SOLVD mus sib hais qhia tau hais tias, piv rau cov placebo, ACE-Kuv tsis txo qhov poob ntawm eGFR, uas zoo sib xws nyob rau hauv ob pawg. Txawm li cas los xij, txoj kev tshawb fawb pom zoo kom tsis txhob tshem tawm ACE-I hauv cov neeg mob uas tsis tshua muaj thiab nruab nrab eGFR poob vim muaj txiaj ntsig zoo rau tag nrho cov txiaj ntsig CV [24]. Tsis tas li ntawd, ob qho tib si ACE-I thiab ARBs tau pom tias ua rau qeeb qeeb ntawm eGFR poob hauv ntshav qab zib thiab nephropathy vim lawv cov txiaj ntsig zoo ntawm lub cev [25](Table 2).

Hauv cov neeg mob hauv sinus atherosclerosis nrog HF thiab LVEF<50%, b-blockers="" reduced="" mortality="" versus="" placebo="" without="" any="" deterioration="" in="" renal="" function="" over="" time="" in="" patients="" with="" moderate="" or="" moderate="" to="" severe="" renal="" impairment="" [26].="" these="" beneficial="" results="" were="" lost="" in="" patients="" with="" hf="" and="" atrial="" fibrillation(af)at="" any="" level="" of="" egfr.="" metoprolol="" was="" analyzed="" in="" three="" renal="" function="" subgroups="" and="" demonstrated="" an="" effective="" reduction="" in="" all-cause="" death="" and="" hospitalizations="" for="" worsening="" hif="" in="" patients="" with=""><45 ml/min/1.73="" m²="" and="" egfr="" 45="" to="" 60ml/min/1.73="" m²,="" as="" in="" those="" with="" egfr="">60 mL / min / 1.73 m² [27]. Meta-analyses los ntawm CAPRICORN (carvedilol postinfarct ciaj sia taus tswj nyob rau hauv sab laug ventricular dysfunction kawm) thiab COPERNICUS (carvedilol prospective randomized, cumulative ciaj sia taus txoj kev tshawb fawb) pom tau hais tias carvedilol tau zoo zam nyob rau hauv cov neeg mob uas muaj thiab tsis muaj CKD, nrog rau ib tug nce nyob rau hauv cov txheeb ze ntawm infarction. nce nyob rau hauv cov ntshav creatinine, tsis muaj teebmeem rau lub raum loj thiab hloov electrolyte hauv cov neeg mob CKD. Kev kho Carvedilol txo cov txiaj ntsig sib xyaw ntawm CV kev tuag lossis HF mus pw hauv tsev kho mob, tsis muaj kev cuam tshuam tseem ceeb ntawm kev tuag sai sai thaum muaj mob me me mus rau nruab nrab CKD[28]. Carvedilol txo morbidity thiab tuag nyob rau hauv cov neeg mob dialyzed nrog dilated cardiomyopathy [29]. Cov kev tshawb pom sib txawv tam sim no qhia tau hais tias kev siv B-blockers hauv kev lim ntshav lossis hauv cov neeg mob lub raum tsis zoo yuav tsum tau tshawb xyuas ntxiv (Table 3).

Keeb kwm, MRAs tau suav hais tias yog contraindicated rau cov neeg mob lub raum tsis ua haujlwm, vim tias muaj kev pheej hmoo siab ntawm hyperkalemia. Cov txiaj ntsig zoo ntawm ob qho tib si spironolactone thiab eplerenone ntawm cov txiaj ntsig ntawm HF cov neeg mob tsis ntev los no tau txuas ntxiv rau cov neeg mob raum tsis ua haujlwm; Txawm li cas los xij, tsis muaj kev sim siab tsom rau qhov cuam tshuam ntawm MRAs ntawm lub raum qhov tshwm sim thiab kev tuag cuam tshuam rau cov neeg mob HF thiab eGFR.<30ml in/1.73m2="" [30].="" a="" recently="" published="" secondary="" analysis="" of="" the="" eplerenone="" in="" mild="" patients="" hospitalized="" and="" a="" survival="" study="" in="" heart="" failure="" (emphasis-hf)="" examined="" the="" beneficial="" and="" adverse="" effects="" of="" eplerenone="" on="" renal="" function.="" even="" though="" patients="" with="" an=""><50 ml/min/1.73m2="" were="" assigned="" lower="" target="" doses="" of="" eplerenone="" (25="" mg="" versus="" 50="" mg),="" the="" drug="" showed="" a="" beneficial="" effect="" on="" the="" outcome="" versus="" placebo;="" however,="" patients="" with="" egfr="" 30-49ml/min/1.73m²="" experienced="" higher="" incidences="" of="" hyperkalemia,="" renal="" failure,="" and="" drug="" discontinuation="" [31]patients="" with="" moderate="" renal="" dysfunction="" should="" be="" monitored="" closely="" after="" the="" initiation="" of="" an="" mras,="" with="" frequent="" k="" analyses="" and="" a="" slower="" up-titration="" of="" therapy,="" due="" to="" the="" higher="" risk="" of="" hyperkalemia="" and="" the="" potential="" arrhythmic="" and="" renal="" consequences.="" mras="" treatment="" did="" not="" affect="" renal="" function="" in="" subjects="" without="" evidence="" of="" hf;="" finerenone,="" a="" non-steroidal="" selective="" mra,="" resulted="" in="" a="" lower="" risk="" of="" ckd="" progression="" and="" cv="" events="" than="" placebo="" in="" patients="" with="" ckd="" and="" type="" two="" diabetes="" [32].="" the="" aforementioned="" data="" reinforced="" the="" use="" of="" mras="" in="" patients="" with="" either="" hf="" and="" mild="" to="" moderate="" ckd,="" or="" in="" patients="" with="" high="" cv="" risk="" associated="" with="" renal="" dysfunction,="" but="" a="" larger="" use="" in="" more="" advanced="" hf="" and="" ckd="" stages="" was="" not="" extensively="" carried="" out,="" and="" it="" deserves="" specific="">

Hauv cov neeg mob uas muaj HF, cov txiaj ntsig zoo ntawm ARNI tau pom ntau lub cev lub cev, suav nrog kev nce hauv intracellular cyclic GMP uas tawm tsam qhov cuam tshuam ntawm tubule-glomerular tawm tswv yim ntawm afferent arteriole. Hauv kev txheeb xyuas rov qab los ntawm qhov kev sib piv yav tom ntej ntawm ARNI nrog ACE-i los txiav txim qhov cuam tshuam rau kev tuag thoob ntiaj teb thiab kev mob plawv hauv plawv tsis ua haujlwm (PARADIGM-HF) kev sim, sacubitril thiab valsartan txhim kho CV cov txiaj ntsig thiab ua rau qeeb qeeb ntawm eGFR poob qis piv rau enalapril. (qhov sib txawv ntawm 0.4 mL/min/1.73 m² ib xyoos). Piv txwv li [33]. Qhov txiaj ntsig ntawm qhov txiaj ntsig tau loj dua hauv cov neeg mob ntshav qab zib ntau dua li cov tsis muaj [34]. Cov txiaj ntsig no kuj tau lees paub hauv cov neeg mob HFpEF, uas sacubitril thiab valsartan txo qhov kev pheej hmoo ntawm ntau dua lossis sib npaug li 50 feem pua. Kev txo qis hauv eGFR, kab mob raum kawg, lossis kev tuag los ntawm lub raum ua rau, thiab txo qis hauv eGFR thaum lub sijhawm ua raws li valsartan. Cov txiaj ntsig ntawm lub raum tau pom tseeb dua hauv cov neeg mob LVEF nruab nrab ntawm 30-60 feem pua; ho wever, tag nrho cov pej xeem nyob rau hauv txoj kev tshawb no tau ntsib ib tug eGFR txo ntawm 1.8 mL / min / 1.73 m² ib xyoo nyob rau hauv pawg sacubitril thiab valsartan, piv rau 2.4mL / min / 1.73m² ib xyoo nyob rau hauv RAAS inhibitors pawg, tsis hais LVEF [35 ].

SGLT-2 co-transporters yog nyob rau hauv lub raum proximal convoluted tubule; los ntawm inhibiting Na plus thiab qabzib reabsorption, SGLT-2 inhibitors txhawb glucosuria thiab natriuresis thiab txo cov kua dej ntxiv thiab cov ntshav plasma. Cov teebmeem no txo ​​qis sab laug ventricular afterload thiab preload thiab txo cov ntshav siab thiab arterial txhav thaum txhim kho cov kev kawm-endocardial ntshav txaus [36]. Lub raum hemodynamic cuam tshuam ntawm SGLT-2 inhibition tau sau tseg rau kev txo qis hauv lub siab glomerular. Cov nyhuv ntawm SGLT-2 los tiv thaiv glomerular hypertension thiab hyperfiltration yog qhov tseem ceeb hauv hom ob ntshav qab zib mellitus (T2DM), qhov twg hyperglycemia ua rau lub raum Na ntxiv rau reabsorption, ua rau lub raum tsis zoo rau vasodilatory teb los ntawm kev tawm tswv yim tubuloglomerular [37] Empaglifozin txhim kho. mob ntshav qab zib raum los ntawm kev txo qis mitochondrial fission ntawm AMPK/SP1/PGAM5 txoj hauv kev [38,39]. Nrog rau tag nrho cov txiaj ntsig zoo no, SGLT-2 inhibitors ua rau muaj kev tiv thaiv nephron thiab txo qis kev mob ntshav qab zib nephropathy. Ntxiv mus, sodium-hydrogen exchanger 3 (NHE3) yog qhia nyob rau hauv lub proximal tubule thiab exchanges Na ntxiv rau hauv lub cell nrog proton export [40]. NHE3 nce qhov kev qhia ntawm SGLT-2 nyob rau hauv nephron membrane, ua rau sympathetic/RAAS activation thiab acidosis. Kev kho ntawm Na plus homeostasis kuj nyob ntawm qhov inhibition ntawm lub raum NHE3 los ntawm SGLT-2 inhibitors. Thaum kawg, hauv kev tshuaj ntsuam meta-kev soj ntsuam ntawm cov kev sim ntsuas randomized, SGLT-2 txo qis albuminuria, ua rau qeeb ntawm microalbuminuria mus rau macroalbuminuria thiab txo qhov kev pheej hmoo ntawm cov kab mob raum kawg.

Nyob rau hauv xyoo tas los no, qhov kev sim ua pov thawj tau tsim cov txiaj ntsig CV thiab lub raum cov txiaj ntsig ntawm SGLT-2 inhibitors hauv cov pej xeem HFrEF. Cov txiaj ntsig ntawm empagliflozin tau sim hauv cov neeg mob uas muaj lub plawv tsis ua haujlwm thiab txo qis ejection feem (EMPEROR-Reduced) qhia tias empagliflozin txo qis CV tuag thiab HF mus pw hauv tsev kho mob hauv cov neeg mob HFrEF, txawm tias OMT. Kev sim suav nrog cov neeg mob uas muaj eGFR siab dua 20 mL / min / 1.73 m, thiab 48 feem pua ​​​​ntawm cov neeg kawm tau txais eGFR<60 ml/min/1.73="" m².="" empagliflozin="" reduced="" the="" primary="" outcome="" and="" the="" total="" number="" of="" hf="" hospitalizations="" in="" patients="" with="" and="" without="" ckd,="" and="" had="" the="" beneficial="" effect="" of="" reducing="" the="" decline="" of="" renal="" function,="" regardless="" of="" the="" severity="" of="" renal="" function="" at="" baseline="" [43].="" the="" analyses="" of="" the="" credence="" (canagliflozin="" and="" renal="" events="" in="" diabetes="" with="" established="" nephropathy="" clinical="" evaluation)trial="" showed="" the="" effects="" of="" canagliflozin="" in="" reducing="" the="" incidence="" of="" kidney-related="" adverse="" events="" in="" patients="" with="" t2dm="" and="" ckd[44].="" moreover,="" the="" dapagliflozin="" and="" prevention="" of="" adverse="" outcomes="" in="" heart="" failure="" (dapa-hf)="" trial="" included="" 41%of="" patients="" with=""><60 ml/min/1.73="" m²="" and="" excluded="" those="" with=""><25 ml/min/1.73="" m².="" the="" results="" of="" the="" trial="" showed="" that="" the="" benefits="" of="" dapagliflozin="" on="" morbidity="" and="" mortality="" in="" hfref="" did="" not="" differ="" by="" egfr="" category="" or="" by="" examining="" egfr="" as="" a="" continuous="" variable,="" with="" a="" significantly="" slower="" rate="" of="" decline="" in="" egfr,="" regardless="" of="" the="" presence="" of="" diabetes="" [46].="" in="" the="" dapa-ckd(dapagliflozin="" and="" prevention="" of="" adverse="" outcomes="" in="" chronic="" kidney="" disease)="" trial,="" properly="" designed="" for="" patients="" with="" ckd,="" dapagliflozin="" significantly="" reduced="" the="" decline="" in="" egfr,="" the="" end-stage="" kidney="" disease,="" or="" death="" from="" renal="" or="" cv="" causes="" [47](table="">

Hauv kev xyaum kho mob, raws li tau pom hauv ntau qhov kev sim, qhov pib ntawm SGLT-2inhibitors tau cuam tshuam nrog qhov pib qis qis ntawm qe rover hauv thawj lub lis piam. Qhov kev txo qis hauv eGFR yog thim rov qab, thiab lub raum ua haujlwm maj mam rov qab mus rau nws cov theem pib, nrog rau kev ruaj khov ntawm lub raum ua haujlwm thaum ua raws. Thawj qhov kev poob qis hauv eGFR yuav tsum tsis txhob ua rau kev txiav tawm ntxov ntxov ntawm SGLT-2 inhibitors kev kho mob.

Tsis ntev los no, cov kev kho tshiab hauv HFrEF tau thov. Kev tshawb fawb thoob ntiaj teb ntawm vericiguat hauv cov neeg mob plawv tsis ua hauj lwm nrog kev txo qis ejection feem (VICTORIA) kev sim ua kom pom cov txiaj ntsig ntawm vericiguat, soluble guanylate cyclase stimulator, hauv kev txo qis cov txiaj ntsig tseem ceeb ntawm CV tuag lossis HF tsev kho mob. Thawj thawj zaug hauv kev kho HF, txoj kev tshawb no suav nrog cov neeg mob eGFR siab dua 15 mL / min / 1.73 m² 2; cov txiaj ntsig zoo ntawm vericiguat tau zoo ib yam thoob plaws tag nrho ntawm eGFR, tsis hais ntawm WRF [48].

Kev siv hydralazine thiab isosorbide dinitrate (H-ISDN) hauv HFrEF tsis tshua muaj siv hauv kev kho mob. Txawm li cas los xij, kev kho mob nrog H-ISDN tau pom zoo nyob rau hauv cov lus qhia kawg rau cov neeg mob HFrEF uas tsis kam ua rau RAAS inhibitors, thiab hauv cov neeg mob African-American HFrEF uas muaj cov tsos mob txawm tias kev kho mob neurohumoral zoo. Kev kho mob nrog H-ISDNis muaj kev nyab xeeb rau cov neeg mob CKD. Txawm li cas los xij, hauv kev sim tsis ntev los no, H-ISDN nyob rau sab saum toj ntawm cov txheej txheem kho mob tsis tau txhim kho kev tawm dag zog hauv cov neeg mob cardiorenal syndrome thiab HFrEF [49]. Cov kev tshawb pom no tau pom zoo nrog cov ntaub ntawv hauv ntiaj teb no ntawm ib pawg loj ntawm HFpEF thiab HFmrEF cov neeg mob uas tau cuv npe hauv Swedish Heart Failure Registry qhov twg cov neeg mob hauv pawg neeg soj ntsuam nrog HF thiab CKD (eGFR 30-59} mL/min/1.73 m² thiab eGFR<30 ml/min/1.73="" m²）benefitted="" from="" nitrate="">