Èske KDIGO sib tansyon sistolik la<120 MmHg For Chronic Kidney Disease Appropriate in Routine Clinical Practice?

REZIME:Gestion méticuleux de tansyon wo enpòtan nanmaladi ren kwonik (CKD)pouredwi risk pou maladi kadyovaskilè, mòtalite, akpwogresyon CKD. Gid ki fèk pibliye Kidney Disease Improving Global Outcomes (KDIGO) sou jesyon tansyon (BP) nan CKD ensiste sou enpòtans estanda mezi BP ak kontwòl strik sou BP. Sa a se yon dokiman itil ki pral ede amelyore jesyon tansyon wo nan CKD globalman. Sepandan, rekòmandasyon an nan yon sib BP sistolik nan<120 mmHg by KDIGO is controversial. It is based on weak evidence derived mainly from a single randomized controlled trial and its CKD subgroup analysis. Here, we review the current evidence surrounding BP target in CKD. We argue that the target recommended by KDIGO is not generalizable to the majority of people with CKD. Standardized BP measurements are challenging to implement outside specialist hypertension and research clinics, and the target of <120 mmHg BP systolic cannot be extrapolated to routine clinic BP measurements. If applied to routine BP measurement, this target will expose the multimorbid and frail CKD patients to the risk of adverse events including falls and fractures. Furthermore, it will not be achievable in the majority of CKD patients. The target recommended by KDIGO is an outlier among contemporary major international hypertension guidelines and is likely to perplex clinicians. We believe the KDIGO-recommended target systolic BP <120 mmHg for CKD is inappropriate in the majority of CKD patients and it may even be harmful for patients managed in routine clinical practice.

NOUVO FÒMILASYON ÈRBAL POU CKD

Tansyon wo se yon faktè risk enpòtan pou tou demaladi kadyovaskilè (CVD)epimaladi ren kwonik (CKD).1 Li se yon gwo kontribisyon toupwogresyon nan CKD.2,3Anplis de sa, CKD seasosye ak yon gwo risk pou CVD, tèlman bagay ke pou yon pasyan ki gen etap 3 CKD, risk pou yo mouri akòz CVD depase byen lwen sa yo ki nan fen etap maladi ren.3,4 Se poutèt sa, kontwòl metikuleu nan tansyon wo enpòtan anpil pou diminye risk CVD nan CKD ak ralanti. pwogresyon CKD.

Kidney Disease Improving Global Outcome (KDIGO) se yon òganizasyon mondyal san bi likratif ki devlope epi ede aplike direktiv pratik klinik ki baze sou prèv pou amelyore "swen ak rezilta pasyan ki gen maladi ren atravè lemond." Nan mwa mas 2021, li te pibliye Gid Pratik Klinik pou Jesyon Tansyon (BP) nan CKD,5 ki se yon aktyalizasyon gid anvan yo nan 20126. Objektif la se te evalye prèv aktyèl la sou mwayen optimal pou mezire BP ak jesyon. nan BP segondè nan pasyan CKD ki gen ladan dyabetik ak nondiabetic CKD, transplantasyon ren, ak CKD nan popilasyon an pedyatrik. Sa a se yon dokiman itil nan 92 paj ki fouye byen fon nan baz la prèv nan domèn yo mansyone pi wo a. Gid la rekòmande pou "granmoun ki gen tansyon wo ak CKD dwe trete ak yon sib tansyon sistolik (SBP) nan<120 mmHg, when tolerated, using a standardized office BP." This recommendation has prompted debates among nephrologists across the globe as to how appropriate this target BP is in day-to-day clinical practice. In this article, we have gone through the available evidence and argue that this target is based on tenuous evidence, not generalizable, and raises significant safety concerns.

FÒS PRÈV

Rekòmandasyon sa a te klase pa gwoup travay direktiv yo kòm nivo 2, se sa ki, yon rekòmandasyon ki "gen chans pou mande deba sibstansyèl ak patisipasyon moun ki gen enterè yo anvan yo ka detèmine politik la" ak nivo bon jan kalite B, ki sijere li se soutni pa modere. - kalite prèv. Rekòmandasyon sa a baze sou yon sèl esè kontwole owaza (RCT) ki byen fèt nan popilasyon jeneral la, SPRINT (Systolic Blood Pressure Intervention Trial),7, ak analiz sougwoup CKD li yo.8

SPRINT randomize 9361 moun ki pa dyabetik, ki gen plis pase 50 ane ak omwen 1 faktè risk CVD, nan entansif (SBP,<120 mmHg) and standard (<140 mmHg) arms. The study was terminated early after an average follow-up of 3.36 years because of substantial CVD and mortality benefits in the intensive BP arm. Participants in the intensive arm were found to be at 25% lower relative risk of the primary outcome-a composite of myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or CV death. There was a 27% relative risk reduction of all-cause death.7 The CKD subgroup (n=2646) analysis, which was respectful, showed a 28% relative risk reduction of all-cause death but no risk reduction in the composite primary CVD outcome or the composite kidney outcome (drop in eGFR of ≥50% from baseline or end-stage kidney disease). Furthermore, there was a more rapid decline in the estimated glomerular filtration rate (eGFR) over the first 6 months in the intensive BP group, which continued, albeit at an attenuated rate, beyond the sixth month.8

SPRINT pa t gen pouvwa pou analiz sougwoup yo,7 epi li te fini bonè. Te gen yon risk ogmante nan aksidan ren egi nan bra entansif BP la. Menmsi pa te gen okenn modifikasyon efè fòmèl pa CKD, rediksyon risk (-18%) nan rezilta prensipal CV nan sougwoup CKD a te mwens pwononse pase nan popilasyon an san CKD (-30%). Gwoup travay gid la te deklare "risk: rapò benefis pou rezilta ren nan bra SBP entansif la ka pa osi favorab nan sougwoup sa a tankou nan sougwoup ki gen pi wo eGFR debaz la."7 Yon analiz post hoc nan SPRINT kap gade eGFR ak risk la. -benefis pwofil entansif kontwòl BP nan mitan pasyan ki pa dyabetik yo te jwenn ke se benefis CV nan kontwòl strik BP atténue pa pi ba eGFR tandiske li pa t 'modifye efè a sou AKI. Nan 968 pasyan yo ak eGFR<45 ml/min/1.73 m2, there was no reduction in CV risk in the intensive BP group compared with the standard BP group (hazard ratio [HR], 0.92 [95% CI, 0.62–1.38]), whereas it increased the risk of AKI (HR, 1.73 [95% CI, 1.12–2.66]).9

Sèl esè ki konpare sib BP ki ba yo te teste nan SPRINT (SBP,<120 mm Hg) with standard BP control (<140 mmHg) in diabetic patients was the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes).10 This trial failed to show any benefit of intensive BP control except a reduction in the risk of developing nonfatal stroke. Moreover, ACCORD included a few participants with significant CKD. Rightly, the guideline work group stated, "There is little evidence from ACCORD alone to guide a recommendation for patients with diabetes and CKD."7 Three recent systematic reviews and meta-analyses looked at the benefit of intensive BP control in CKD. The first one compared intensive BP control (<130/80 mmHg) with standard BP control (<140/90 mmHg) on major renal outcomes in patients with CKD without diabetes. It included 9 major hypertension trials with 8127 participants, including SPRINT, which looked at the progression of CKD. Over a median of 3.3 years of follow-up, there was no additional benefit of intensive BP control on renal outcomes.11 The second carried out a meta-analysis of 18 randomized clinical trials (including SPRINT and ACCORD) comprising 15924 patients with CKD, more intensive BP lowering (achieved mean SBP, 132 versus 140 mmHg) was associated with significantly lower (HR, 0.86 [95% CI, 0.63–0.99]) risk of mortality compared with less intensive BP control.12 The most recent of these studies pooled individual data on 4983 participants from 4 major hypertension and CKD trials, including SPRINT and ACCORD, testing the impact of intensive BP target (SBP, <130 mmHg) compared with the standard target (SBP, <140) on all-cause mortality. On primary analysis, there was no significant difference between the groups in the primary outcome of all-cause mortality or the secondary outcomes of CV composite endpoint and CV mortality.13 After excluding those with eGFR >60 mL/min pou chak 1.73 m2 ak tretman glisemi entansif, te parèt gen yon pi ba risk pou tout kòz mòtalite nan gwoup entansif BP (HR, 0.79 [95% CI, 0.63). –1.00]). Nan meta-analiz sa yo, la<120 mmHg threshold was not tested, probably because ACCORD and SPRINT, that is, the two sole large trials testing such a threshold, produced highly heterogeneous results.

Yon rezo meta-analiz sou 26 esè tansyon wo (ki gen ladan SPRINT, ACCORD, aktout gwo esè CKD BP) evalye rezilta efikasite konjesyon serebral, enfaktis myokad, lanmò,kadyovaskilè lanmòh, ensifizans kadyak, ak rezilta sekirite nan efè negatif grav ki gen ladan angioedema, ipotansyon, senkop, bradikardya / aritmi, oswa ipo / ipèkalimi. Bra esè yo te gwoupe nan 5 kategori sib SBP:<160, <150, <140, <130, and <120 mmHg. There was no difference in death, cardiovascular death, or heart failure when comparing any of the BP targets. The point estimates favored lower BP targets (<120 and <130 mmHg) when compared with higher BP targets (<140 or <150 mmHg). However, there were significantly higher incidence rates of serious adverse effects with lower BP targets. On-treatment SBP target of <130 mmHg achieved optimal balance between efficacy and safety.14 This has been further supported by a recent trial, which tested whether intensive BP control (SBP, 110–130 mmHg) is superior to standard BP control (130–150 mmHg) in reducing the risk of CV events in 9624 Chinese patients (19% diabetic, 196 patients with eGFR <60 mL/min per 1.72 m2), aged between 60 and 80 years. The mean achieved BP in the two groups was 127.5 and 135.3 mmHg, respectively. There was a 26% relative risk reduction (HR, 0.74 [95% CI, 0.60–0.92]) of primary composite CV endpoint, without an increase in adverse events except for more hypotension in the intensive BP control arm. Importantly, there was no difference between the groups in terms of renal outcomes.15

Ansanm ak prèv ki prezante pi wo a, nou ta diskite ke pa gen ase prèv pou sipòte rekòmandasyon ke "granmoun ki gen tansyon wo ak CKD dwe trete ak sib tansyon sistolik (SBP) nan.<120 mmHg, when tolerated, using a standardized office BP." The quality of evidence underpinning this recommendation is perhaps low rather than moderate, that is, "the true effect of intensive BP control may be substantially different from the estimate of the effect."

JENERALIZABILITE

Dapre pwotokòl, SPRINT ekskli moun<50 years of age, those with diabetes or proteinuria ≥1 g/ day, adult polycystic kidney disease, glomerulonephritis treated with or likely to be treated with immunosuppressive therapy, and those with eGFR <20 mL/min per 1.73 m2. The mean eGFR in SPRINT was 48 mL/min per 1.73 m2, and it included a few patients with CKD stage 4. Of the cases of CKD that were excluded in SPRINT, diabetes is the commonest cause of CKD accounting for 42% of cases across the world. Glomerulonephritis accounts for ≈20% followed by adult polycystic kidney disease (around 10%).16,17 We have also seen that the ACCORD trial did not show any benefit of intensive BP control on CVD and death, except a reduction in nonfatal stroke, in people with diabetes. Therefore, strictly speaking, the KDIGO-recommended target SBP <120 mmHg may not apply to the vast majority of patients with CKD the nephrologists care for.

SEKIRITE sib BP ki ba a

Gid KDIGO BP rekòmande pou yo mezire BP nan moun ki gen CKD nan yon fason ofisyèl. Yon biwo estandadize BP esansyèlman se yon mwayèn de 2 oswa 3 mezi BP yo pran lè l sèvi avèk yon aparèy valide, apre omwen 5 minit nan repo nan yon anviwònman trankil. Gid KDIGO a sijere ke pasyan yo ta dwe evite kafeyin, fè egzèsis, ak fimen pou omwen 30 minit anvan mezi. Li sijere tou asire ke pasyan an te vide nan blad pipi yo anvan mezi.5 Kontrèman, woutin biwo mezi BP (yo rele tou aksidantèl BP) pa enkli okenn preparasyon anvan yo pran lekti yo. SPRINT ak lòt esè tansyon wo ki sot pase yo te itilize lekti BP estanda paske yo korelasyon byen ak mezi BP ki pa nan biwo a. Nou kwè rekòmandasyon KDIGO pou mezire BP nan yon fason ofisyèl apwopriye; yo ta dwe fè yon efò pou mezire BP nan yon fason ofisyèl chak fwa yo mezire BP. Sepandan, pi souvan pase pa, nan pratik klinik nephrologists konte sou woutin biwo BP. Lekti biwo yo souvan siyifikativman pi wo pase mezi estanda BP ak lekti BP anbilatwa oswa lakay yo, sitou akòz efè blan-rad la, 18 ki afekte plis pase 50% nan pasyan ki gen tansyon wo trete, diferans mwayèn ant klinik ak anbilatwa BP se 20 mmHg. 19 Anplis de sa, mezi estanda BP yo byen korelasyon ak domaj nan fen ògàn yo. 20 Yon etid ki gade konkòdans ant BP nan SPRINT ak sa ki te jwenn nan pratik klinik woutin, ki soti nan dosye sante elektwonik, te demontre ke te gen yon akò ki ba ant de yo ak entèval lajè akò. sòti nan -30 jiska +45 mmHg. Enteresan, diferans lan te pi wo nan gwoup tretman entansif la konpare ak gwoup tretman estanda a (diferans mwayen, 7.3 kont 4.6 mmHg).21 Nan kontèks CKD, biwo estanda BP se, an mwayèn, 12.7 mmHg pi ba pase BP nan biwo woutin, ak limit lajè nan akò (-46.1 a 20.7 mmHg).22 Limit yo lajè nan akò ant woutin ak estanda mezi BP mete aksan sou diferans ki genyen nan pasyan endividyèl yo. Kontinwe, pa gen okenn faktè koreksyon pou estime estanda BP ka aplike nan BP woutin. Apwopriye, Gwoup Travay Gid la te deklare ke li ta ka potansyèlman danjere pou aplike sib SBP la<120 mmHg nonstandardized BP measurements to office BP measurements, the most frequently used metric in nephrology clinics across the world, as there is a risk of overtreatment.

Danje potansyèl ki genyen nan BP sib ki ba, espesyalman lè yo aplike nan mezi BP woutin, gen ladan ogmante risk pou ipotansyon postural, tonbe renouvlab, ak ka zo kase, blesi egi nan ren, konjesyon serebral nan moun ki gen pi ba rezèv karotid, ak n bès rapid nan eGFR nan moun ki gen renovaskulèr. maladi.23 Pasyan CKD yo gen yon risk pi gwo pou evènman sa yo pase popilasyon jeneral la paske anpil nan yo se granmoun aje, frajil, ak miltimorbid.14 Pri moun ak sosyete a nan tonbe se menmen. Pri imen an gen ladan doulè, blesi, detrès, pèt konfyans, ak yon pi gwo risk lanmò. Youn nan 3 moun ki gen yon ka zo kase anch mouri nan yon ane, byenke pi fò nan lanmò yo pa lakòz dirèkteman pa ka zo kase, men pito sante ki kache nan ki tonbe a ka yon siy. Nan Wayòm Ini a, tonbe koute sèvis sante nasyonal UK (NHS) 2 milya £ pa ane ak 4 milyon jou kabann.24 Ozetazini, nan 2014, total depans swen sante pèsonèl pou granmoun aje te varye ant $48 milyon dola nan Alaska a $4.4 milya dola nan Kalifòni. Depans Medicare ki ka atribiye a tonbe nan granmoun aje yo te varye ant $22 milyon dola nan Alaska ak $3.0 milya dola nan Florid.25

Sanble, AKI nan SPRINT te modere ak revèsib epi yo te atribiye a efè emodinamik. Sepandan, nou pa konnen ki efè alontèm AKI/eGFR n bès ak bese BP entansif se sitou nan moun ki gen CKD avanse.26 Sa a se patikilyèman konsa paske peryòd swivi yo relativman kout nan esè kontwòl entansif BP. Nan SPRINT, AKI te siyifikativman pi wo nan moun ki gen eGFR<45 mL/min per 1.73 m2 than in those with higher eGFR9; there were few participants with stage 4 CKD. Monitoring for electrolyte disturbances and AKI may also be less frequent in routine clinical practice compared with clinical trials. Therefore, the guideline should have highlighted the importance of close follow-up of these patients.