An é Sprioc Brú Fola Systolic KDIGO<120 MmHg For Chronic Kidney Disease Appropriate in Routine Clinical Practice?
Aug 14, 2024
Teibí:Tá bainistiú cúramach ar Hipirtheannas tábhachtach igalar duáin ainsealach (CKD)chuiglaghdú ar an mbaol galar cardashoithíoch, mortlaíocht, agusdul chun cinn CKD. Leagann an treoirlíne um Fheabhsú Torthaí Domhanda a Fheabhsú Galar Duán (KDIGO) ar bhainistíocht brú fola (BP) i CKD béim ar an tábhacht a bhaineann le tomhas caighdeánaithe BP agus rialú docht ar BP. Is doiciméad úsáideach é seo a chuideoidh le feabhas a chur ar bhainistiú Hipirtheannas i CKD ar fud an domhain. Mar sin féin, moladh sprioc BP systolic de<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.
Is fachtóir riosca tábhachtach é Hipirtheannas don dá cheanngalar cardashoithíoch (CVD)agusgalar duáin ainsealach (CKD).1 Cuireann sé go mór ledul chun cinn CKD.2,3Ina theannta sin, tá CKDbainteach le riosca ard CVD, an oiread sin ionas go sáraíonn othar le céim 3 CKD an baol báis de bharr CVD ná an riosca a bhaineann le galar duáin deiridh. dul chun cinn CKD.
Is eagraíocht neamhbhrabúis dhomhanda é Galar Duán a Fheabhsú Toradh Domhanda (KDIGO) a fhorbraíonn agus a chabhraíonn le treoirlínte cleachtais chliniciúil atá bunaithe ar fhianaise a chur i bhfeidhm chun "cúram agus torthaí othar a bhfuil galar duáin ar fud an domhain orthu a fheabhsú." I mí an Mhárta 2021, d’fhoilsigh sé an Treoirlíne um Chleachtas Cliniciúil chun Brú Fola a Bhainistiú (BP) i CKD,5 ar nuashonrú í ar an treoirlíne a bhí acu roimhe seo in 20126. Ba é an cuspóir measúnú a dhéanamh ar an bhfianaise atá ann faoi láthair maidir leis na bealaí is fearr chun BP a thomhas agus a bhainistiú. BP ard in othair CKD lena n-áirítear CKD diaibéitis agus neamhdiaibéitis, trasphlandú duáin, agus CKD sa daonra péidiatraiceach. Is doiciméad úsáideach 92 leathanach é seo a théann go domhain isteach sa bhonn fianaise sna réimsí thuasluaite. Molann an treoirlíne “go gcaithfí le daoine fásta a bhfuil BP ard agus CKD orthu brú fola systólach sprice (SBP) de<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.
LÁIDIR NA FIANAIS
Tá an moladh seo grádaithe ag grúpa oibre na dtreoirlínte mar leibhéal 2, is é sin, moladh ar “dócha go mbeidh gá le díospóireacht agus rannpháirtíocht shubstaintiúil ó pháirtithe leasmhara sular féidir an beartas a chinneadh” agus leibhéal cáilíochta B, a thugann le tuiscint go bhfuil measarthacht mar bhonn agus mar thaca aige. -fianaise cáilíochta. Tá an moladh seo bunaithe ar thriail rialaithe randamach dea-stiúrtha amháin (RCT) sa phobal i gcoitinne, SPRINT (Triail Idirghabhála Brú Fola Systolic),7, agus a anailís foghrúpa CKD.8
Rinne SPRINT randamach ar 9361 duine aonair nondiabetic, os cionn 50 bliain d'aois agus ar a laghad 1 fachtóir riosca CVD, go dian (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
Ní raibh SPRINT faoi thiomáint le haghaidh anailísí foghrúpa,7 agus tháinig deireadh leis go luath. Bhí baol méadaithe gortú duáin géarmhíochaine sa lámh BP dian. Cé nach raibh aon mhodhnú foirmiúil éifeacht ag CKD, bhí an laghdú riosca (−18%) de thoradh CV príomhúil san fhoghrúpa CKD níos lú suntasaí ná sa daonra gan CKD (−30%). Luaigh an grúpa oibre treoirlíne “d’fhéadfadh nach mbeadh an cóimheas riosca: tairbhe do thorthaí duáin sa ghéag SBP dian chomh fabhrach san fhoghrúpa seo agus atá san fhoghrúpa a bhfuil bonnlíne níos airde eGFR aige.”7 Anailís post hoc ar SPRINT ag féachaint ar eGFR agus an riosca. - fuarthas amach sa phróifíl sochair de dhianrialú BP i measc othar neamhdiaibéitis go bhfuil an tairbhe CV a bhaineann le rialú dian BP maolaithe ag eGFR níos ísle ach níor athraigh sé an éifeacht ar AKI. Sna 968 othar le 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
An t-aon triail a rinne comparáid idir an sprioc BP íseal a tástáladh i 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/nóiméad in aghaidh 1.73 m2 agus dianchóireáil glycemic, bhí an chuma ar an scéal go raibh riosca níos ísle de mhortlaíocht uilechúiseach sa ghrúpa BP dian (HR, 0.79 [95% CI, 0.63 –1.00]). Sna meiti-anailísí seo, tá an<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.
Meitianailís líonra ar 26 triail Hipirtheannas (lena n-áirítear SPRINT, ACCORD, agusgach triail mhór CKD BP) measúnú ar thorthaí éifeachtúlachta stróc, infarction miócairdiach, bás,bás cardashoithíochh, cliseadh croí, agus torthaí sábháilteachta éifeachtaí díobhálacha tromchúiseacha lena n-áirítear angioedema, fotheannas, sioncóp, bradycardia/airrhythmia, nó hipiteirme/hiperkalemia. Rinneadh airm thrialach a ghrúpáil i 5 chatagóir sprice 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
I dteannta na fianaise a chuirtear i láthair thuas, d’áitímid nach bhfuil dóthain fianaise ann chun tacú leis an moladh “go gcaithfí le daoine fásta a bhfuil BP ard agus CKD orthu le brú fola systólach sprice (SBP) de.<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."
GINEARÁLTA
De réir an phrótacail, daoine aonair eisiata SPRINT<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.
SÁBHÁILTEACHT AN SPRIOC BP ÍSEAL
Molann treoirlíne KDIGO BP gur cheart BP i ndaoine le CKD a thomhas ar bhealach caighdeánaithe. Go bunúsach is éard atá i BP oifige caighdeánaithe ná 2 nó 3 thomhas BP ar an meán a thógtar ag baint úsáide as gléas bailíochtaithe, tar éis 5 nóiméad ar a laghad de scíthe i dtimpeallacht chiúin. Molann treoir KDIGO gur chóir d'othair caiféin, aclaíocht agus caitheamh tobac a sheachaint ar feadh 30 nóiméad ar a laghad roimh an tomhas. Molann sé freisin a chinntiú go bhfuil an lamhnán fholmhú ag an othar roimh an tomhas.5 I gcodarsnacht leis sin, ní chuimsíonn gnáth-thomhas BP oifige (ar a dtugtar BP ócáideach freisin) aon ullmhúchán sula ndéantar na léamha. Bhain SPRINT agus trialacha Hipirtheannas eile le déanaí úsáid as léamha caighdeánaithe BP mar go bhfuil comhghaol maith acu le tomhais BP lasmuigh den oifig. Creidimid go bhfuil moladh KDIGO BP a thomhas ar bhealach caighdeánaithe oiriúnach; ba cheart iarracht a dhéanamh BP a thomhas ar bhealach caighdeánaithe gach uair a thomhaistear BP. Mar sin féin, níos minice ná a mhalairt, i gcleachtas cliniciúil nephrologists ag brath ar BP oifige ghnáthamh. Is minic go mbíonn léamha oifige i bhfad níos airde ná tomhais chaighdeánaithe BP agus léamha BP siúil nó baile, go príomha mar gheall ar éifeacht an chóta bháin,18 a théann i bhfeidhm ar níos mó ná 50% d’othair a bhfuil cóireáil orthu le hipeartheannas, is é 20 mmHg an meándifríocht idir BP cliniciúil agus siúlach. 19 Ina theannta sin, tá comhghaol maith idir tomhais chaighdeánaithe BP agus damáiste orgán deiridh.20 Léirigh staidéar a d'fhéach ar chomhréireacht idir BP in SPRINT agus a fuarthas i ngnáthchleachtas cliniciúil, ó thaifid leictreonacha sláinte, go raibh comhaontú íseal idir an dá cheann le eatraimh chomhaontaithe leathana. sa raon ó −30 go +45 mmHg. Is díol spéise é go raibh an difríocht níos airde sa ghrúpa dianchóireála i gcomparáid leis an ngrúpa cóireála caighdeánach (meándifríocht, 7.3 in aghaidh 4.6 mmHg).21 I gcomhthéacs CKD, tá BP oifige caighdeánaithe, ar an meán, 12.7 mmHg níos ísle ná BP oifige gnáthaimh, le teorainneacha leathana comhaontaithe (−46.1 go 20.7 mmHg).22 Cuireann teorainneacha leathana an chomhaontaithe idir gnáthtomhais agus tomhais chaighdeánaithe BP béim ar an difríocht laistigh d'othair aonair. Dá bhrí sin, ní féidir aon fhachtóir ceartúcháin chun BP caighdeánaithe a mheas a chur i bhfeidhm ar BP gnáthaimh. Mar is cuí, dúirt an Grúpa Oibre Treoirlíne go bhféadfadh sé a bheith guaiseach sprioc an SBP a chur i bhfeidhm<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.
I measc na guaiseacha féideartha a bhaineann le sprioc íseal BP, go háirithe nuair a chuirtear i bhfeidhm é ar ghnáth-thomhas BP, tá riosca méadaithe hypotension postural, titim athfhillteach, agus bristeacha, gortú duáin géarmhíochaine, stróc i measc na ndaoine a bhfuil cúlchiste carotid níos ísle acu, agus meath tapa ar eGFR i measc na ndaoine a bhfuil athnuachan orthu. galair.23 Tá othair CKD i mbaol i bhfad níos airde maidir leis na teagmhais seo ná an daonra i gcoitinne mar go bhfuil go leor acu scothaosta, lag, agus ilghalrach.14 Tá costas daonna agus sochaíoch an-mhór ar thitim. Áirítear leis an gcostas daonna pian, gortú, anacair, cailliúint muiníne, agus baol báis níos mó. Faigheann duine as gach 3 duine le briseadh cromáin bás laistigh de bhliain, cé nach bristeacha go díreach is cúis leis an gcuid is mó de na básanna, ach is é an drochshláinte is cúis leis an titim a d'fhéadfadh a bheith ina chomhartha. Sa Ríocht Aontaithe, cosnaíonn titimí £2 billiún sa bhliain ar Sheirbhís Sláinte Náisiúnta na RA (SNS) agus 4 mhilliún lá leaba. $48 milliún in Alasca go $4.4 billiún i gCalifornia. Bhí caiteachas Medicare inchurtha i leith titimí i ndaoine fásta sa raon ó $22 milliún in Alasca go $3.0 billiún i Florida.25
D'fhéadfaí a mhaíomh, go raibh an AKI i SPRINT éadrom agus inchúlaithe agus cuireadh éifeacht haemdinimiciúil san áireamh. Mar sin féin, níl a fhios againn cén éifeacht fhadtéarmach atá ag meath AKI/eGFR le hísliú dian BP go háirithe dóibh siúd a bhfuil CKD ardleibhéil acu.26 Tá sé seo fíor go háirithe toisc go bhfuil na tréimhsí leantacha sách gearr i dtrialacha dianrialaithe BP. I SPRINT, bhí AKI i bhfad níos airde i measc iad siúd a raibh eGFR acu<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.
