Kev kho mob raum mob raum tsis zoo: Kev Tshawb Fawb Cov Ntaub Ntawv Ntawm Randomized Controlled Trials
Mar 01, 2022
Taw qhia
Kwv yees li 840 lab tus tib neeg thoob ntiaj teb muaj mob ntevmob raum(CKD) [1], uas yog lub luag haujlwm rau 1.2 lab tus neeg tuag thiab 35.8 lab tus neeg xiam oob khab-hloov lub neej xyoo hauv 2017 [2]. Txawm li cas los xij, tsuas yog 12 feem pua ntawm cov neeg mob paub txog lawv tus mob [3]. CKD raug kuaj pom thaum qhov kwv yees glomerular filtration rate (eGFR) poob qis dua 60 mL / min / 1.73 m2 lossis cov zis albumin-to-creatinine ratio (UACR) sib npaug lossis ntau dua 30 mg / g rau 3 lub hlis lossis ntev dua [4]. Raws li CKD vam meej, cov nqi kho mob nce thiab kev noj qab haus huv ntawm lub neej (HRQoL) txo qis, nrog rau cov nqi loj tshaj thiab HRQoL lub nra cuam tshuam nrograum tsis ua haujlwm(eGFR \ 15 mL / min / 1.73 m2 ) [5, 6]. Cov txiaj ntsig tsis zoo hauv kev kho mob, kev siv kev noj qab haus huv thiab cov nqi, thiab cov kab mob hnyav kuj nce ntxiv vim albuminuria zuj zus [7–9], thiab UACR 30–300 mg / g (nruab nrab nce) thiab txawm tias [300 mg / g (nce hnyav) tam sim no suav tias yog qhov tseem ceeb. Kev kwv yees ntawm kev pheej hmoo rau CKD kev loj hlob, kab mob plawv, thiab kev tuag [4]. Kev txheeb xyuas ntxov ntxov thiab kev cuam tshuam ntawm kws tshuaj tuaj yeem ua rau ncua lossis tiv thaiv kev mob CKD. Cov lus qhia tam sim no pom zoo kom siv renin-angiotensin-aldosterone system (RAAS) inhibitors (xws li angiotensin-hloov enzyme inhibitor lossis angiotensin receptor blocker) kom ncua lossis tiv thaiv CKD kev nce qib [4]. Kev sim tshuaj ntawm lwm cov chav kawm tshuaj los txhawb RAAS inhibitors, ncua kev nce qib, thiab txhim kho cov txiaj ntsig tau tsis tshua muaj raws li lawv cov ntsiab lus kawg [10], tshwj tsis yog rau sodium-glucose co-transporter 2 (SGLT2) inhibitors. Thaum xub thawj tsim raws li cov ntshav qabzib cov neeg ua haujlwm txo qis, ceeb toom ntawmlub raumthiab cov txiaj ntsig ntawm cov hlab plawv hauv cov neeg mob uas muaj ntshav qab zib hom 2 (T2D) [11–14] nrog rau cov txiaj ntsig ntawm cov hlab plawv hauv cov neeg mob plawv tsis ua haujlwm (HF) [15–17] tau ua rau muaj kev soj ntsuam ntawm SGLT2 inhibitors hauv cov neeg mob CKD uas twb tau txais. Tus qauv kev kho mob nrog RAAS inhibitors. Qhov kev tshuaj xyuas cov ntaub ntawv no tau tshawb xyuas cov kev kho mob tshuaj ntsuam xyuas hauv cov neeg mob CKD txij li xyoo 1990 los tso cai rau kev ntsuam xyuas cov ntaub ntawv tam sim no ntsig txog kev kho mob tag nrho.
Ntsiab lus:Albuminuria; Kev tuag tag nrho; Mob raum mob; Mob ntshav qab zib; Kwv yees glomerular pom tus nqi; Lub raum tsis ua haujlwm; lub raum
CISTANCHE yuav txhim kho rau lub raum/ raum mob
Txoj kevQhov kev tshuaj xyuas cov ntaub ntawv no tau ua raws li cov lus pom zoo ntawm Cochrane [18], Lub Chaw Saib Xyuas thiab Kev Tshaj Tawm [19], thiab National Institute for Health and Care Excellence [20]. Cov txheej txheem tau sau npe rau ntawm PROSPERO (CRD42020190152). Kab lus no yog ua raws li cov kev tshawb fawb yav dhau los thiab tsis muaj cov kev tshawb fawb tshiab nrog tib neeg koom lossis tsiaj ua los ntawm ib tus kws sau ntawv.
Cov ntaub ntawv qhov chaw thiab tshawb nrhiavSiv cov lus teev tseg hauv Cov Khoom Siv Ntxiv, peb tau tshawb nrhiav MEDLINE, Embase, thiab Cochrane Library rau cov phooj ywg txheeb xyuas cov ntawv luam tawm thaum xyoo 1990 thiab Kaum Ib Hlis 2, 2020, uas tau tshaj tawm cov txiaj ntsig los ntawm kev cia siab, paralleldesign randomized tswj kev sim uas ntsuas cov tshuaj kho mob rau cov neeg mob hnub nyoog. 18 xyoo lossis ntau dua nrog CKD thiab albuminuria. Tshawb nrhiav cov ntaub ntawv rau MEDLINE thiab Embase tau txais los ntawm Scottish Intercollegiate Guideline Network [21], thiab hloov kho rau Embase los ntawm Cochrane [22]. Raws li cov lus qhia rau kev suav nrog cov ntaub ntawv grey [18–20, 23], cov txheej txheem ntawm cov rooj sib tham tseem ceeb thoob ntiaj teb thiab cov ntawv teev npe mus sib hais kuj tau tshawb nrhiav (Cov Khoom Siv Ntxiv). Cov ntawv xov xwm tsis yog lus Askiv, kev tshuaj xyuas, cov ntaub ntawv tshawb fawb, cov ntaub ntawv xov xwm, cov rooj sib tham hauv xov tooj (tshwj tsis yog cov uas tau txheeb xyuas hauv kev tshawb nrhiav tau piav qhia saum toj no), thiab kev tshawb fawb tsiaj raug cais tawm.
Kev xaiv simTom qab tshem cov duplicates los ntawm cov kev tshawb fawb sib xyaw ua ke, ob tus neeg saib xyuas kev ywj pheej tau tshuaj xyuas qhov kev txheeb xyuas qhov tseeb ntawm cov qauv tsim nyog tau teev tseg (Table 1). Cov kev paub daws teeb meem suav tias tsim nyog rau kev suav nrog tom qab ntawd tau muab piv thiab txhua qhov tsis sib xws tau daws qhov sib koom los yog los ntawm tus neeg saib xyuas thib peb. Cov txheej txheem kev tshuaj xyuas ob npaug no tau rov ua dua ntawm cov ntawv sau tag nrho txhawm rau txheeb xyuas cov npe kawg ntawm cov kev sim siab uas tsim nyog rau suav nrog hauv qhov kev tshuaj xyuas no.Cov ntaub ntawv rho tawm thiab Kev Ntsuam Xyuas Cov Ntaub Ntawv Zoo tau muab rho tawm los ntawm ib tus neeg tshuaj xyuas thiab tau lees paub los ntawm ib qho thib ob, nrog kev tsis pom zoo los ntawm ib feem peb (Cov Khoom Siv Ntxiv). Binary variables suav nrog cov neeg sim, tus lej lossis feem pua ntawm cov neeg mob ntsib ib qho xwm txheej, thiab qhov xwm txheej tshwm sim rau ib tus neeg lossis tib neeg lub sijhawm. Nruam thiab lub sij hawm-rau-kev tshwm sim variables suav nrog kev phom sij piv (HR), qhov sib txawv piv txwv, txheeb ze, qhov nruab nrab, qhov sib txawv ntawm tus qauv, tus qauv yuam kev, ntau yam, 95 feem pua ntawm kev ntseeg siab (CI), interquartile range, thiab P tus nqi. Cov txiaj ntsig tau tshaj tawm tsis muaj qhov txiaj ntsig P lossis 95 feem pua CIs tau xav tias tsis yog qhov tseem ceeb. Cov txiaj ntsig tau tshaj tawm nrog P \ 0.05 lossis nrog 95 feem pua CIs tsis hla 1.0 rau HR lossis tus txheeb ze pheej hmoo raug suav tias yog qhov tseem ceeb. Kev pheej hmoo ntawm kev tsis ncaj ncees thiab kev tshaj tawm zoo tau raug soj ntsuam los ntawm yim nqe lus nug los ntawm PMG24 Tuam Txhab Pov Thawj Xa Ntawv Pov Thawj (NICE ib qho txheej txheem kev ntsuam xyuas thev naus laus zis) [24], tsim los ntawm cov lus pom zoo dhau los [19]. Cov lus teb ntawm 'yog' 'tsis yog' 'los yog' 'tsis meej vim tsis txaus qhia' tau xav tau. Nyob ntawm cov lus nug, cov lus teb ntawm 'yog' lossis 'tsis yog', tuaj yeem qhia tias muaj kev pheej hmoo siab dua lossis qis dua ntawm kev tsis ncaj ncees (Cov Khoom Siv Ntxiv).
Ua raws li Cov Cai Tswj Kev Ncaj NceesKab lus no yog ua raws li cov kev tshawb fawb yav dhau los thiab tsis muaj cov kev tshawb fawb tshiab nrog tib neeg koom lossis tsiaj ua los ntawm ib tus kws sau ntawv.
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Tshawb nrhiavZuag qhia tag nrho, 40,550 cov ntaub ntawv raug txheeb xyuas (Daim duab 1). Tom qab tshem tawm ntawm 20,773 duplicates, 19,777 abstracts raug tshuaj xyuas los ntawm cov qauv tsim nyog, thiab 19,557 raug tshem tawm. Cov ntawv sau tag nrho ntawm 220 kab lus raug tshuaj xyuas, thiab 121 raug cais tawm (Table S1). Qhov sib ntxiv ntawm ib tsab xov xwm ntxiv, txheeb xyuas thaum tshawb nrhiav cov rooj sib tham hauv lub rooj sib tham, tau ua rau 100 cov khoom tsim nyog muab cov ntaub ntawv rau 89 qhov kev sim ntsuas randomized (Table 2). luam tawm ua ntej 2010. Plaub caug-peb sim (48.3 feem pua) yog theem 3 (n=29), theem 4 (n=10), theem 2/3 (n=3), los yog theem 3/4 (n=1), thiab feem ntau yog ob qhov muag tsis pom (61.8 feem pua) lossis qhib daim ntawv lo (32.6 feem pua) (Fig. S1a, b). Plaub caug-rau qhov kev sim siab (51.7 feem pua) tsis tau tshaj tawm lawv cov theem sim. Cov kev sim no feem ntau tau tso npe rau 50-100 tus neeg mob ib sab caj npab, txawm hais tias 10 tau ua dhau los ntawm 2004 tau tso npe ntau dua 1000 tus neeg mob hauv ib caj npab [25–27, 34, 47, 60, 73–75, 93]. Plaub caug-peb qhov kev sim (48.3 feem pua) tau sau npe rau cov neeg mob T2D, 29 cov neeg mob rau npe nrog lossis tsis muaj T2D (32.6 feem pua), thiab 17 tus neeg mob rau npe tsis muaj T2D (19.1 feem pua). Thoob plaws txhua qhov kev sim, 75.5 feem pua ntawm cov neeg mob muaj T2D (Fig. S2a, b). Txhua tus neeg mob tau ua raws li tsawg kawg 12 lub lis piam, txawm hais tias qhov kev soj ntsuam nruab nrab lossis nruab nrab txuas ntxiv mus rau tsawg kawg 12 lub hlis hauv 60 qhov kev sim (67.4 feem pua) thiab tsawg kawg 24 lub hlis hauv 38 qhov kev sim (42.7 feem pua).
Antihypertensive agents yog qhov kev cuam tshuam ntau tshaj plaws tau soj ntsuam tag nrho, tab sis muaj kwv yees li ob npaug ntawm kev sim ntawm cov neeg mob uas tsis muaj T2D (88 feem pua) dua li kev sim ntawm cov neeg mob (42 feem pua), lossis nrog lossis tsis muaj (45 feem pua) T2D. Cov tshuaj txo cov ntshav qabzib kuj tseem muaj nyob rau hauv kev sim ntawm cov neeg mob T2D (37 feem pua). Cov neeg sib piv feem ntau yog cov placebo hauv kev sim ntawm cov neeg mob T2D (53 feem pua) thiab cov neeg sib piv sib piv hauv cov neeg mob uas tsis muaj (53 feem pua), lossis nrog lossis tsis muaj (38 feem pua) T2D. Cov placebo kuj tseem muaj nyob rau hauv kev sim ntawm cov neeg mob uas tsis muaj (35 feem pua), lossis nrog lossis tsis muaj (34 feem pua) T2D (Fig. S3a, b).
Cov yam ntxwv ntawm tus neeg mob BaselineHauv ntau dua 80 feem pua ntawm kev sim, 50–1{{20}}0 feem pua ntawm cov neeg mob yog txiv neej (Fig. S4). Lub hnub nyoog nruab nrab yog 51.0–72.1 xyoo hauv kev sim cov neeg mob uas muaj lossis tsis muaj T2D (tshwj tsis yog ib qho kev sim nrog lub hnub nyoog nruab nrab ntawm 34–35 xyoo [82]), 53.8–70. 2 xyoos hauv kev sim ntawm cov neeg mob T2D (tshwj tsis yog ib qho kev sim nrog lub hnub nyoog nruab nrab ntawm 34.0-35.0 xyoo [66], thiab ib qho kev sim nrog lub hnub nyoog nruab nrab ntawm 33 xyoo [65]), thiab 44.4-71.0 xyoo hauv kev sim cov neeg mob tsis muaj T2D. Thaum CKD etiologies uas tsis yog mob ntshav qab zib nephropathy feem ntau tau tshaj tawm hauv kev sim ntawm cov neeg mob T2D, 13 qhov kev sim (14.6 feem pua) ntawm cov neeg mob tsis muaj T2D thiab 16 (18.0 feem pua) ntawm cov neeg mob uas muaj lossis tsis muaj T2D qhia txog glomerulonephritis raws li ib qho tseem ceeb ntawm CKD etiology, Table S. b). Qhov nruab nrab eGFR nyob nruab nrab ntawm 13.9 thiab 102.8 mL / min / 1.73 m2, suav nrog ob qhov kev sim uas tau tso npe rau cov neeg mob uas txhais tau tias eGFR [90 mL / min / 1.73 m2 (Table S3) [38, 59]. Kev sim feem ntau tshaj tawm albuminuria li UACR (50.6 feem pua), nrog rau UACR qhov nruab nrab ntawm 29.9 thiab 2911.0 mg / g. Lwm qhov kev sim qhia UACR los ntawm kev faib ua normo-, micro-, lossis macroalbuminuria (16.9 feem pua), albumin excretion rate (12.4%), protein excretion rate (20.2%), protein-to-creatinine ratio (18.0%), los yog tso zis albumin. tus nqi (13.5%) (Table S4a–f).
CISTANCHE yuav txhim kho lub raum / raum ua haujlwm
Peb caug-ib qhov kev sim (34.8 feem pua) suav nrog cov neeg mob uas muaj keeb kwm yav dhau los ntawm cov kab mob plawv, nrog rau kev faib ua feem ntawm cov neeg mob li ntawm 1.7 feem pua mus rau 92 feem pua. Tab S5). Kaum plaub qhov kev sim (15.7 feem pua) suav nrog cov neeg mob HF, nrog rau cov neeg mob feem ntau ntawm 0.6 feem pua rau 43.1 feem pua (Table S6). Yim caum-ob qhov kev sim (92.1 feem pua) qhia txog systolic thiab diastolic ntshav siab (Table S7).
Cov txiaj ntsig sib xyawTsib caug xya lub ntsiab lus xaus tau raug txheeb xyuas, tsuas yog 13 qhov uas tau siv ntau tshaj ib qhov kev sim (Fig. S5a, b). Cov txiaj ntsig sib xyaw tau sau tseg hauv Table S8. Kaum ob qhov kev sim siab (13.5 feem pua) qhia txog qhov txo qis hauv kev pheej hmoo ntawm cov khoom sib xyaw uas suav nrograum tsis ua haujlwmNtxiv rau ib lossis ntau dua ntawm cov ntshav creatinine, eGFR txo qis (C 40 feem pua lossis C 50 feem pua), kev tuag (txhua yam ua rau,lub raum,los yog mob plawv), myocardial infarction (MI), mob stroke, albuminuria progression, los yog lwm yam (Table 3). Cov no suav nrog kev sim luam tawm ua ntej 2013 ntsuas RAAS inhibitors losartan (RENAAL, ROAD) [61, 112], ramipril (REIN-1, AASK) [115, 123], irbesartan (IDNT) [62], valsartan (KVT) [83], thiab benazepril (ROAD, thiab kev sim tsis muaj npe) [112, 113] hauv cov neeg mob uas muaj, tsis muaj, lossis nrog lossis tsis muaj T2D. Tsis tas li ntawd suav nrog cov kev sim luam tawm txij li xyoo 2019 los ntsuas dipeptidyl peptidase 4 inhibitor linagliptin (CARMELINA) [34], endothelin A receptor antagonist atrasentan (SONAR) [47], thiab cov non-steroidal mineralocorticoid receptor antagonist fifinerenone (FID) Hauv cov neeg mob T2D, nrog rau SGLT2 inhibitor canagliflflozin (CREDENCE) [27] hauv cov neeg mob T2D thiab UACR [300-5000 mg / g. Lwm qhov SGLT2 inhibitor, dapagliflflozin, qhov tseem ceeb txo qhov kev pheej hmoo ntawm cov ntsiab lus sib xyaw ua ke suav nrog.raum tsis ua haujlwmthiab tsawg kawg yog 50 feem pua eGFR txo ntxiv rau cov hlab plawv thiab / lossislub raumKev tuag hauv cov neeg mob uas muaj lossis tsis muaj T2D thiab UACR 200-5000 mg / g (DAPA-CKD) [25].Lub raum tsis ua haujlwmRaws li cov txiaj ntsig ntawm kev ywj pheej tau tshaj tawm hauv qab Plaub qhov kev sim (4.5 feem pua) qhia txog qhov txo qis hauv kev pheej hmoo ntawm kev sib xyaw ua ke suav nrog kev tuag ntawm cov hlab plawv yam tsis muajraum tsis ua haujlwm, ntxiv rau yam tsawg kawg ib ntawm ob npaug ntawm cov ntshav creatinine,lub raumKev tuag, MI, mob stroke, pw hauv tsev kho mob rau HF, lossis pw hauv tsev kho mob rau HF lossis tsis ruaj khov angina (Table 3). Cov no suav nrog CARMELINA [34], FIDELIO-DKD [26], thiab CREDENCE [27] kev sim, nrog rau kev sim DAPA-CKD ntawm dapagliflflozin, uas ua rau txo qis qhov kev pheej hmoo ntawm kev sib xyaw ua ke suav nrog kev mob plawv thiab kev mus pw hauv tsev kho mob rau HF [ 25] ib. Conversely, qhov kev pheej hmoo ntawm kev sib xyaw ua ke suav nrog kev tuag ntawm cov hlab plawv thiab mus pw hauv tsev kho mob rau HF lossis tsis ruaj khov angina tau nce hauv BEACON sim ntawm bardoxolone methyl, ib qho khoom siv nuclear 1 (erythroid-derived 2)- cuam tshuam txog 2 activator, txawm hais tias cov neeg mob hauv qhov kev sim no tau muaj. CKD theem 4, T2D, thiab nruab nrab UACR 320 mg/g [73].
Cov txiaj ntsig rau lub raum Lub raum FailureLub raum tsis ua haujlwm(yav dhau los kawg-theemmob raumlos yog kawg-theemmob raum[124]) tshwm sim thaum eGFR poob qis dua 15 mL / min / 1.73 m2 (CKD theem 5) thiab tus neeg mob xav tauraumhloov kho (yav dhau loslub raumHloov kho [124]) hauv daim ntawv hloov pauv lossis lim ntshav [4]. Peb caug-ob qhov kev sim (36.0 feem pua ) tau tshaj tawm tus lej ntawm cov neeg mob nce musraum tsis ua haujlwm(Table S9). Cov kev pheej hmoo txo qis tau pom nyob rau hauv xya qhov kev sim (7.9 feem pua): RENAAL sim ntawm losartan hauv cov neeg mob T2D thiab UACR C 30{{30}} mg/g (P {{5}) }.002) [61], ROAD sim ntawm qhov zoo tshaj plaws antiproteinuric koob tshuaj losartan (P=0.046) thiab benazepril (P=0.042) hauv cov neeg mob uas tsis muaj T2D [112], ib qho kev sim tsis muaj npe ntawm kev siv tshuaj benazepril hauv cov neeg mob uas tsis muaj T2D (P=0.02) [113], REIN-1 thiab AASK kev sim ntawm ramipril hauv cov neeg mob tsis muaj T2D (ob leeg P=0.01) [ 115, 118], CREDENCE sim ntawm canagliflflozin (P=0.002) [27], thiab DAPACKD sim ntawm dapagliflflozin (HR 0.64; 95% CI 0.50–0.82) [25].
Dialysis thiab TransplantationDialysis,hloov raum, lossis ob qho tib si tau tshaj tawm hauv 17 (19.1 feem pua), xya (7.9 feem pua), thiab ob qhov kev sim (2.2 feem pua), raws li (Table S10). Cov txiaj ntsig tseem ceeb raug txwv rau peb qhov kev sim (3.4 feem pua). Tus neeg saib xyuas lipid-lowering probucol lengthened txhais tau tias lub sij hawm los pib lim ntshav hauv kev sim ntawm cov neeg mob T2D thiab UACR [ 3{{20}}0 mg/g (P=0.009 ) [71], thiab tus naj npawb ntawm cov neeg mob pib lim ntshav tau txo qis hauv kev sim ntawm cov neeg mob uas tsis muaj T2D tau txais RAAS inhibitor captopril (P \0.005) [121], nrog rau cov neeg mob tau txais dapagliflflozin hauv DAPACKD sim (HR 0.66; 95% CI 0.48–0.90) [25].
Lub raum ua haujlwm poob qisQhov feem pua eGFR poob qis, txhais tau tias eGFR poob qis, thiab qhov kawg ntawm eGFR ntsuas qhov kawg ntawm kev ua raws li tau tshaj tawm hauv 11 (12.4 feem pua), 30 (33.7 feem pua), thiab 25 (28.1 feem pua) kev sim, raws li (Table S11a–c ). Tus naj npawb ntawm cov neeg mob ncav cuag eGFR poob ntawm 50 feem pua yog txo qis hauv plaub qhov kev sim (4.5 feem pua): SONAR sim ntawm atrasentan hauv cov neeg mob T2D thiab UACR 300–5000 mg / g (P=0.038) [47], tus Tswv sim ntawm lipid-txo tus neeg saib xyuas atorvastatin hauv cov neeg mob uas muaj lossis tsis muaj T2D (P=0.023) [95], thiab DAPA-CKD kev sim ntawm dapagliflozin (HR 0.53; 95% CI 0.42–0.67) [25]. Hauv kev sim PREDICT ntawm erythropoiesis-stimulating tus neeg sawv cev darbepoetin alfa, tus naj npawb ntawm cov neeg mob uas tsis muaj T2D ncav cuag eGFR poob ntawm 50 feem pua tseem ceeb kuj txo qis ntawm cov hom phiaj siab dua (11-13 g / dL) piv rau qis dua (9-11 g / dL) qib hemoglobin (P=0.008); Txawm li cas los xij, kev tsom mus rau qib siab hemoglobin tsis tau txhim khoraumcov txiaj ntsig tag nrho [106]. Tus naj npawb ntawm cov neeg mob mus txog qhov eGFR poob tsawg kawg yog 40 feem pua tau txo qis hauv FIDELIODKD sim ntawm fifinerenone (HR 0.81; 95 feem pua CI 0.72–0.92) [26].
Nees nkaum qhov kev sim (22.5 feem pua) qhia cov neeg mob ob npaug ntawm lawv cov ntshav creatinine (Table S12). Qhov kev pheej hmoo txo qis tau pom nyob rau hauv xya qhov kev sim (7.9 feem pua : SONAR sim ntawm atrasentan (P=0). {13}}.68; 95% CI 0.55–0.82) [26], RENAAL trial of losartan (P=0.006) [61], the ROAD sim ntawm qhov zoo tshaj plaws antiproteinuric koob tshuaj ntawm losartan (P=0.040) thiab benazepril (P=0.041) [112], ib qho kev sim tsis muaj npe ntawm cov koob tshuaj benazepril (P=0). 02).
CISTANCHE yuav txhim kho lub raum / raum mob
Lub plawv tsis ua hauj lwmKaum plaub qhov kev sim (15.7 feem pua) qhia txog qhov tshwm sim ntawm HF (Table S13), nrog kev txo qis hauv ob qhov kev sim (2.2 feem pua): ASCEND sim ntawm endothelin hom A receptor antagonist avosentan hauv cov neeg mob T2D (P=0.008). nrog rau 25-mg koob, P=0.05 nrog ib koob 50-mg) [57] thiab IDNT sim ntawm irbesantan (P=0}.004 vs amlodipine, P=0.048 vs placebo) [64].Kev mus pw hauv tsev kho mob rau HF lossis Unstable AnginaKev mus pw hauv tsev kho mob rau HF thiab pw hauv tsev kho mob rau qhov tsis ruaj khov angina tau tshaj tawm hauv 10 (11.2 feem pua) thiab ob qhov kev sim (2.2 feem pua), raws li (Table S14). Kev txo qis hauv tsev kho mob rau HF tau pom nyob rau hauv ob qhov kev sim (2.2 feem pua) : RENAAL sim ntawm losartan (P=0.005) [61] thiab CREDENCE sim ntawm canagliflflozin (P \ 0.001) [27]. Hloov pauv, bardoxolone methyl tseem ceeb nce mus pw hauv tsev kho mob rau HF hauv kev sim BEACON (P \ 0.001) [73].MI thiab StrokeNees nkaum plaub qhov kev sim (27. Kev txo qis hauv MI tau pom nyob rau hauv cov neeg mob uas tau txais calcium channel blocker amlodipine hauv kev sim IDNT (P=0.021 vs placebo) [64]. Kev txo qis hauv cov hlab ntsha tsis txaus ntshai tau pom nyob rau hauv SONAR sim ntawm atrasentan (P=0.0021) [47], thiab txo qhov tseem ceeb hauv ischemic (P=0.0073) lossis ib qho mob stroke (P=0.01) tau pom nyob rau hauv SHARP qhov kev sim ntawm kev sib xyaw ntawm lipid-txo cov tshuaj simvastatin thiab ezetimibe hauv cov neeg mob uas muaj lossis tsis muaj T2D [93]. Hloov pauv, qhov tseem ceeb ntawm kev tuag los yog tsis muaj mob stroke tau pom nyob rau hauv TREAT sim ntawm cov neeg mob nrog CKD theem 3-4 thiab T2D tau txais darbepoetin alfa (P \ 0.001) [75].
Cov txiaj ntsig kev tuagAll-Cause MortalityRau caum-peb qhov kev sim (70.8 feem pua) tau tshaj tawm tag nrho-ua rau kev tuag (ACM) (Table S17), nrog kev txo qis tseem ceeb hauv DAPA-CKD sim ntawm dapagliflflozin (P=0.004) [25].Mob plawv thiab lub raum tuagCardiovascular thiablub raumCov neeg tuag tau tshaj tawm hauv 18 (20.2 feem pua) thiab cuaj qhov kev sim (10.1 feem pua), raws li, tsis muaj cov txiaj ntsig tseem ceeb (Table S18).Lwm cov txiaj ntsig rau lub raumeGFR SlopeseGFR slopes tau tshaj tawm hauv 15 qhov kev sim (16.9 feem pua), nrog rau eGFR poob qis tseem ceeb hauv peb qhov kev sim (3.4 feem pua): RENAAL sim ntawm losartan (P=0.01) [61], kev sim tsis muaj npe ntawm benazepril ( P=0.006) [113], thiab REIN{11}} sim ntawm ramipril (P=0.036) [118] (Table S19).AlbuminuriaUACR kev hloov pauv los ntawm cov hauv paus ntsiab lus thiab qhov kawg ntawm UACR kev ntsuas thaum kawg ntawm kev soj ntsuam tau tshaj tawm hauv 20 (22.5 feem pua) thiab 17 (19.1 feem pua) kev sim, raws li (Table S20a, b). Qhov tseem ceeb UACR txo qis los ntawm cov hauv paus ntsiab lus tau pom nyob rau hauv yim qhov kev sim (9.0 feem pua : GUARD, ASCEND, AWARD{{10}}} thiab EMPA-REGRENAL sim ntawm dipeptidyl peptidase 4 inhibitor gemigliptin (P \0.001) [39], avosentan 25 lossis 50 mg (P \0.001) [57], glucagon-zoo li peptide-1 receptor agonist dulaglutide 1.5 mg (P=0.0024) ) [37], thiab SGLT2 inhibitor empagliflflozin 25 mg (P=0.0257–0.0031) [42], raws li, hauv cov neeg mob T2D; unnamed trials ntawm calcium channel blocker benidipine (P \0.0001 vs amlodipine) [84] thiab xanthine oxidase inhibitor topiroxostat (P=0.0092) [79] hauv cov neeg mob uas muaj lossis tsis muaj T2D; ACCOMPLISH sim ntawm kev sib xyaw ntawm benazepril thiab amlodipine (P=0.0001 vs benazepril ua ke nrog hydrochlorothiazide) hauv cov neeg mob uas muaj lossis tsis muaj T2D [85]; thiab EVALUATE kev sim ntawm kev xaiv aldosterone antagonist eplenerone hauv cov neeg mob uas tsis muaj T2D (P=0.0222) [107].
Thaum qhov kawg ntawm UACR ntsuas qhov kawg ntawm kev soj ntsuam tau siv, qhov tseem ceeb txo qis hauv UACR los ntawm cov hauv paus ntsiab lus tau pom nyob rau hauv plaub qhov kev sim (4.5 feem pua): kev sim tsis muaj npe ntawm lipid-txo tus neeg sawv cev rosuvastatin hauv cov neeg mob T2D (P \0). . RENAAL sim ntawm losartan (P \ 0.001) [61], thiab kev sim tsis muaj npe ntawm benidipine (P \ 0.01 vs amlodipine) hauv cov neeg mob uas muaj lossis tsis muaj T2D [84].Health-Related Quality of LifeTsib qhov kev sim (5.6 feem pua) [75, 97, 99, 100] qhia HRQoL thaum kho. Hauv ib qho kev sim (1.1 feem pua),Kab mob raumthiab Kev Ua Haujlwm Zoo ntawm Lub Neej Cov qhabnias ntawm lub cev ua haujlwm tau zoo dua qub los ntawm qhov pib (P \ 0}.0001) hauv cov neeg mob CKD thiab metabolic acidosis kho nrog veverimer, thawj zaug hauv chav kawm hydrochloric acid binder [104].
Kev Txiav Txim Thaum NtxovKaum qhov kev sim (11.8 feem pua) raug tso tseg thaum ntxov vim muaj kev nrhiav neeg ua haujlwm tsawg lossis cov xwm txheej tsawg (n=2) [47, 100], kev txhawj xeeb txog kev nyab xeeb (n=5) [53, 57, 73, 74, 115], cov txiaj ntsig tsis zoo tau tshaj tawm hauv tus muam sim (n=1) [72], lwm yam laj thawj (n=1) [61], lossis yog vim li cas tsis muab (n=1) [ 113] ib. Raws li cov lus qhia ntawm pawg saib xyuas cov ntaub ntawv ywj pheej, CREDENCE [27] thiab DAPA-CKD [25] kev sim tau raug tso tseg thaum ntxov tom qab tau ntsib cov txheej txheem ua tau zoo rau kev txiav tawm ntxov thiab tom qab dab ntxwg nyoog ua kom muaj txiaj ntsig zoo, feem.Risk of Bias AssessmentRau xya ntawm yim nqe lus nug, 65-100 feem pua ntawm kev sim ua "qis" lossis "tsis meej" qhov kev pheej hmoo ntawm kev tsis ncaj ncees, thaum 35 feem pua ntawm kev sim tsis yog ob npaug qhov muag tsis pom thiab yog li ntawm "siab dua" kev pheej hmoo ntawm kev tsis ncaj ncees. Muaj peev xwm tsis sib haum xeeb ntawm kev txaus siab tau txheeb xyuas hauv 57 feem pua ntawm kev sim (Fig. S6a, b). Cov txiaj ntsig kev nyab xeeb kev nyab xeeb muaj nyob rau hauv Table S21. Qhov siab tshaj plaws tag nrho cov xwm txheej ntawm kev kho mob ntsig txog cov xwm txheej tsis zoo (AEs) tau tshaj tawm hauv kev sim ntawm phosphodiesterase hom 5 inhibition rau cov neeg mob ntshav qab zib nephropathy (lub caj npab nquag, 54.7 feem pua; placebo caj npab, 56.3 feem pua) [49]. Hauv qhov kev sim no, feem ntau cov kev kho mob ntsig txog AEs tshwm sim hauv cov placebo caj npab, thiab suav nrog mob taub hau (7.8 feem pua), raws plab (3.6 feem pua), dyspepsia (3.6 feem pua), thiab peripheral edema (1.6 feem pua) [49]. Qhov siab tshaj plaws ntawm qhov tshwm sim ntawm AEs loj tshaj plaws tau tshaj tawm nyob rau hauv TREAT sim ntawm darbepoetin alfa (active caj npab, 61.6 feem pua; placebo caj npab, 60.4 feem pua), uas tau nres ntxov vim muaj kev txhawj xeeb txog kev nyab xeeb [75]. Qhov loj tshaj plaws AE, tshaj tawm hauv cov placebo caj npab, yog kub siab (24.5 feem pua) [75].
Kev sib tham
89 qhov kev sim tshuaj ntsuam xyuas tau txheeb xyuas los ntawm qhov kev tshuaj xyuas cov ntaub ntawv no suav nrog ntau yam ntawm cov neeg mob uas muaj theem ntawm CKD (eGFR 13.9–102.8 mL/min/1.73 m2) thiab albuminuria (UACR 29.9–2911.0 mg/g) , nrog (75.5 feem pua) lossis tsis muaj (20.6 feem pua) T2D. Ntau qhov kev sim tshuaj ntsuam xyuas qhov cuam tshuam ntawm kev kho mob ntawm ib lossis ntau qhov sib xyaw ua ke, thiab 16 qhov kev sim tau qhia txog qhov txo qis hauv kev pheej hmoo ntawm cov khoom sib xyaw uas muaj xws liraum tsis ua haujlwm(n=12) lossis kev tuag ntawm cov hlab plawv tsis muajraum tsis ua haujlwm(n=4) thaum ntsuas RAAS inhibitors, SGLT2 inhibitors, fininerenone, lossis lwm yam tshuaj. Txawm li cas los xij, cov kev sib xyaw no tau muaj ntau haiv neeg thiab ntsuas hauv ntau tus neeg mob, cuam tshuam kev sib piv.
Clinically objective ywj siab cov txiaj ntsig, xws liraum tsis ua haujlwmthiab ACM, tau raug txhais ntau dua. Ntawm 32 qhov kev sim qhia txog qhov xwm txheej ntawmraum tsis ua haujlwm, xya pom qhov kev pheej hmoo tseem ceeb txo qis tom qab kev kho mob. Cov no suav nrog kev sim me me ntawm losartan (n=751) hauv cov neeg mob T2D [61] thiab plaub qhov kev sim me me ntawm losartan, benazepril, thiab ramipril (n=84-436) hauv cov neeg mob uas tsis muaj T2D [112, 113, 115, 118], tag nrho luam tawm ua ntej 2008. Yog li ntawd, RAAS inhibition tau los ua tus qauv kev saib xyuas rau cov neeg mob CKD [4]. Txawm li cas los xij, tau muaj qhov tsis muaj kev vam meej hauv kev tsim cov neeg ua haujlwm tshiab los txhawb RAAS inhibitors, ncua kev nce qib, thiab txhim kho cov txiaj ntsig, nrog rau kev sim ntawm lwm cov chav kawm tshuaj tsis tshua ua tau raws li lawv cov ntsiab lus kawg kom txog rau thaum tsis ntev los no. Ob qhov kev sim loj (n=2152 thiab 2202) tau tshaj tawm txij thaum 2019 tau pom tias yuav txo tau qhov txaus ntshai ntawmraum tsis ua haujlwmntawm cov neeg mob nrog UACR C 200 mg / g kho nrog SGLT2 inhibitors [25, 27]. Thaum qhov kev sim CREDENCE ntawm canagliflozin tsuas yog tso npe cov neeg mob nrog T2D, DAPA-CKD kev sim ntawm dapagliflflozin tau pom tiasraum-kev tiv thaiv los ntawm SGLT2 inhibition tuaj yeem txuas ntxiv rau cov neeg mob uas muaj lossis tsis muaj T2D [25]. Ib qho kev txo qis hauv ACM tau pom nyob rau hauv tib qhov kev sim ntawm dapagliflozin yog tib qho piv txwv ntawm kev ua kom ntev ntawm kev muaj sia nyob tau tshaj tawm rau cov neeg mob CKD [25], thiab cov pov thawj los ntawm kev tshuaj xyuas tsis ntev los no tau lees paub tias kev sim tshuaj ntsuam xyuas zoo yuav tsum tau ua. Txhim kho cov kev kho mob uas twb muaj lawm kom ua tau raws li qhov xav tau tsis tau txais [125].
Lub raum tsis ua haujlwmthiab lwm cov txiaj ntsig kev kho mob tau tsim kho lig hauv CKD, xav tau kev sim nrog lub sijhawm ntev los tso npe rau cov neeg mob loj [10]. Surrogate endpoints tuaj yeem siv los saib xyuas tus kab mob kev loj hlob thiab ntsuas kev noj tshuaj hauv cov theem ua ntej ntawm CKD [10, 126–129]. Txawm li cas los xij, qhov kev tshuaj xyuas no tau txheeb xyuas ntau qhov sib txawv ntawm qhov kawg ntawm tus neeg sawv cev, suav nrog cov kev hloov pauv eGFR los ntawm cov hauv paus ntsiab lus (33.7 feem pua), qhov kawg ntawm eGFR qhov tseem ceeb ntawm qhov kawg ntawm kev rov qab (28.1 feem pua), eGFR nqes hav (16.9%), thiab feem pua eGFR poob los ntawm lub hauv paus. (12.4 feem pua). Cov kev sim tshuaj ntsuam xyuas yav tom ntej uas ntsuas cov kev kho tshiab rau cov neeg mob nyob rau theem ua ntej ntawm CKD yuav tau txais txiaj ntsig los ntawm kev ua qauv ntawm cov ntsiab lus surrogate.
CISTANCHE yuav txhim kho lub raum / raum mob ntshav qab zib
Thaum nws tau pom nyob rau lwm qhov uas HRQoL poob qis nrog kev nce qib ntawm CKD [5, 6], qhov kev tshuaj xyuas no qhia txog qhov tsis txaus ntawm cov ntaub ntawv qhia tias kev txhim kho nrog kev kho mob nrog kev txhim kho hauv HRQoL. Tsuas yog tsib qhov kev sim (5.6 feem pua) tau txheeb xyuas tias tau soj ntsuam HRQoL thaum kho, nrog kev txhim kho tseem ceeb txwv rau kev sim ntawm hydrochloric acid binder rau cov neeg mob metabolic acidosis [104]. Teeb meem kev ntes cov kev hloov pauv hauv HRQoL, suav nrog tus naj npawb ntawm cov cuab yeej siv thiab qhov sib txawv ntawm lawv qhov rhiab heev, tau qhia tsis ntev los no [6].
Qhov kev tshuaj xyuas no muaj ntau qhov kev txwv, suav nrog kev tshem tawm cov ntawv tshaj tawm tsis yog lus Askiv thiab kev sim rau cov neeg mob uas tsis muaj albuminuria. Theem tsis tau tshaj tawm nyob rau hauv 51.7 feem pua ntawm kev sim, thiab nws muaj peev xwm hais tias qee qhov kev sim theem 2 tau suav nrog cov qauv tsim nyog. Qhov "siab dua" kev pheej hmoo ntawm kev tsis ncaj ncees tau txheeb xyuas rau 35 feem pua ntawm cov kev sim uas tsis yog qhov muag tsis pom ob. Thaum kawg, cov txheej txheem tsim nyog tau dav dav thiab qhov kev tshuaj xyuas no suav nrog cov neeg mob uas muaj theem ntawm CKD, nrog lossis tsis muaj T2D, thiab tau kho nrog txhua chav tshuaj txij li xyoo 1990. CKD etiologies txawv ntawm cov neeg mob uas muaj T2D thiab tsis muaj T2D, thiab ntau hom kev sib piv yog kuj tau txheeb xyuas. Surrogate thiab soj ntsuam lub hom phiaj ntsuas kev poob qislub raum ua haujlwmthiab kev kho mob tau zoo kuj tau hloov zuj zus mus, thiab 57 qhov sib txawv sib txawv tau txheeb xyuas. Muab qhov dav thiab ntau haiv neeg ntawm cov ntaub ntawv tau txais, kev ua haujlwm ntawm metaanalysis tau suav tias yog qhov ua tsis tau.
XAIV
Txog thaum tsis ntev los no, tsuas yog RAAS inhibitors tau pom tias lawv tuaj yeem ncua CKD kev loj hlob thiab txo qhov kev pheej hmoo ntawmraum tsis ua haujlwm; Txawm li cas los xij, cov pov thawj no tau tsim nyob rau hauv ib qho kev sim me me ntawm cov neeg mob T2D thiab plaub qhov kev sim me me ntawm cov neeg mob tsis muaj T2D. Cov ntaub ntawv tam sim no los ntawm CREDENCE, DAPA-CKD, thiab FIDELIO-DKD kev sim qhia tias ntxiv qhov tsim nyog SGLT2 inhibitor lossis fifinerenone nyob rau sab saum toj ntawm tus qauv kev saib xyuas RAAS inhibition tuaj yeem txhim kho ntau yam ntawm ob qho tib si.raumthiab cov txiaj ntsig ntawm cov hlab plawv hauv cov neeg mob uas muaj lossis tsis muaj T2D. Ntxiv mus, cov ntaub ntawv los ntawm DAPA-CKD qhia tias dapagliflflozin ntxiv rau tus qauv ntawm kev saib xyuas RAAS inhibition tuaj yeem txo qis txhua qhov ua rau tuag rau cov neeg mob uas muaj lossis tsis muaj T2D. Muab qhov kev mob hnyav thiab kev tuag ntawm CKD, qhov cuam tshuam ntawm CKD kev nce qib ntawm HRQoL thiab cov nqi kho mob, thiab kev pheej hmoo ntau ntxiv xws li ntshav siab thiab ntshav qab zib hauv cov neeg laus, cov chav kawm tshuaj tshiab no muaj lub luag haujlwm tseem ceeb hauv kev kho mob yav tom ntej thiab kev tswj hwm ntawm CKD.
