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Ciljani krvni tlak●kronična bolest bubrega●hipertenzija

I dalje se raspravlja o optimalnim ciljevima krvnog tlaka (BP) za bolesnike s hipertenzijom i kroničnom bubrežnom bolešću (CKD). Smjernice American Heart Association/American College of Cardiology (AHA/ACC) iz 2017. izmijenile su definiciju/klasifikaciju hipertenzije i uvele intenzivan ciljni tlak od<130/80 mmHg for most individuals at high risk of cardiovascular disease, including patients with CKD [1]. The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommended an even tighter systolic BP target of <120 mmHg for the management of hypertension in CKD [2]. Which, therefore, is the BP threshold that indicates a therapeutic benefit in this high-risk patient population?

Prema relevantnim studijama, cistanča je tradicionalna kineska biljka koja se stoljećima koristi za liječenje raznih bolesti. Znanstveno je dokazano da posjeduje protuupalna, anti-age i antioksidativna svojstva. Istraživanja su pokazala da je cistanča korisna za bolesnike koji boluju od bolesti bubrega. Poznato je da aktivni sastojci cistanche smanjuju upalu, poboljšavaju rad bubrega i obnavljaju oštećene bubrežne stanice. Stoga, integracija cistanche u plan liječenja bolesti bubrega može ponuditi velike prednosti pacijentima u upravljanju njihovim stanjem. Cistanche pomaže smanjiti proteinuriju, snižava BUN i razine kreatinina te smanjuje rizik od daljnjeg oštećenja bubrega. Osim toga, cistanche također pomaže u smanjenju razine kolesterola i triglicerida što može biti opasno za pacijente koji boluju od bolesti bubrega.

Kliknite na Cistanche Tubulosa za bolesti bubrega

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In this issue of Hypertension Research, Suzuki et al. [3] reported the results of a large retrospective observational study that aimed to explore the association of BP with the risk of developing cardiovascular disease in 188,837 Japanese adults with dipstick proteinuria and an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2. These individuals were categorized into 4 groups following the classification of hypertension that was introduced in the 2017 AHA/ACC guidelines. During a mean follow-up period of 1050 days, 7039 individuals reached the prespecified primary cardiovascular outcome, defined as the composite of myocardial infarction, angina pectoris, stroke, and heart failure. The analysis was conducted separately for individuals who were not taking BP-lowering medications (n = 173,833) and those who were receiving anti-hypertensive treatment (n = 15,004) [3]. Among drug-naive individuals, compared with the category of normal BP, the multivariable-adjusted hazard ratio (HR) for the primary cardiovascular outcome was 1.07 [95% confidence interval (CI): 0.97–1.17] in the category of elevated BP, 1.30 (95% CI: 1.21–1.40) in stage 1 hypertension and 2.17 (95% CI: 2.01–2.34) in stage 2 hypertension [3]. Among drug-treated individuals, compared with the reference category of patients with a normal BP range, the multivariate-adjusted HR for the composite cardiovascular outcome was 1.00 (95% CI: 0.82–1.23), 0.97 (95% CI: 0.83–1.14) and 1.19 (95% CI: 1.02–1.38) in those with elevated BP, stage 1 and stage 2 hypertension, respectively [3]. This dose-response relationship was consistent in the restricted cubic spline analysis. In the subgroup of drug-naive individuals, the cardiovascular risk was progressively increased after the cutoff point of 120/80 mmHg. Among individuals taking BP-lowering medications, an indication of increased cardiovascular risk was observed only when the BP levels were >140/90 mmHg [3].

Jedan pristup definiranju hipertenzije i identificiranju optimalnih terapijskih ciljeva je procjena razine krvnog tlaka o riziku od nepovoljnih zdravstvenih ishoda, kao što je učinjeno u velikoj opservacijskoj studiji Suzukija i sur. [3]. Među pojedincima koji uzimaju lijekove za snižavanje krvnog tlaka, ova je analiza pokazala da kategorija hipertenzije stadija 1, kako je definirana u smjernicama AHA/ACC iz 2017., ne identificira bolesnike s većim rizikom od razvoja kardiovaskularnih bolesti [3]. Ako pretpostavimo da je ova povezanost rizika uzročna, tada intenzivni ciljani krvni tlak od 130/80 mmHg koji je utvrđen u smjernicama AHA/ACC iz 2017. možda nije prikladan za liječenje hipertenzije u bolesnika s proteinuričnom KBB. Uzimajući u obzir da je inherentno ograničenje opservacijskih studija njihova nemogućnost pružanja izravnih uzročno-posljedičnih povezanosti rizika, pouzdaniji pristup definiranju praga terapijske koristi za BP je procjena podataka iz randomiziranih studija koja pokazuju smanjenje rizika od štetni zdravstveni ishodi s intenzivnim protokolima za snižavanje krvnog tlaka.

Compelling clinical trial evidence to demonstrate nephroprotection with lower BP targets is lacking. The Modification of Diet in Renal Disease (MDRD) [4] and the African American Study of Kidney Disease and Hypertension (AASK) [5] were 2 landmark trials that randomly assigned nondiabetic patients with CKD to achieve an intensive (approximately 125/75 mmHg) versus a standard (140/90 mmHg) BP goal. Until the completion of their randomized phase, neither of these 2 trials demonstrated an overall improvement in kidney outcomes with the achievement of tighter BP control [4;5]. However, a sub-group analysis of the MDRD suggested that intensive BP-lowering results were associated with a slower rate of decline in the GFR in patients who had more severe proteinuria (>1 g/dan) na početku [4]. Ideja da proteinurija modificira učinke liječenja intenzivnog snižavanja krvnog tlaka također je podržana post hoc analizom AASK [6]. Nakon završetka probne faze, sudionici AASK-a pozvani su da sudjeluju u kohortnoj studiji nakon suđenja. U ukupnoj analizi i faze ispitivanja i faze kohorte AASK, nije bilo razlike između intenzivne i standardne terapije u riziku od progresije CKD [6]. Međutim, značajno smanjenje relativnog rizika od 27 posto u kompozitnom ishodu bubrega primijećeno je u podskupini sudionika AASK-a koji su imali omjer proteina i kreatinina u urinu > 0.22 g/g na početku [6]. Iako je indikacija nefroprotekcije s intenzivnom kontrolom krvnog tlaka primijećena samo u analizama podskupina, ovi podaci niske kvalitete utjecali su na KDIGO smjernice iz 2012. da daju slabu preporuku razine 2D za strožu ciljnu razinu krvnog tlaka od<130/80 mmHg in proteinuric CKD and a standard BP target of <140/90 mmHg for patients without proteinuric CKD [7].

Objavljeno 2015., Intervencijsko ispitivanje sistoličkog krvnog tlaka (SPRINT) pokazalo je da je među 9361 bolesnika bez dijabetesa s visokim profilom kardiovaskularnog rizika, ciljajući sistolički krvni tlak od<120 mmHg compared with < 140 mmHg provoked a 25% relative risk reduction in fatal and nonfatal cardiovascular events as well as a 27% relative risk reduction in all-cause mortality [8]. A prespecified subgroup analysis that included 2624 SPRINT participants with an eGFR of <60 ml/min/1.73 m2 at baseline showed that the cardioprotective benefit of intensive BP-lowering did not differ between patients with or without CKD [9]. A subsequent subgroup analysis of 1723 SPRINT participants with a urinary albumin-to-creatinine ratio of ≥30 mg/g at baseline also showed that the beneficial effects of intensive BP control on cardiovascular events and all-cause death were similar irrespective of the presence of albuminuria [10]. A slower progression of CKD was not associated with the lower systolic BP target in SPRINT [9]. It must be noted, however, that the prespecified kidney outcome, defined as the composite of sustained ≥ 50% decline in eGFR from baseline or end-stage kidney disease, occurred in only 15 patients in the intensive-treatment arm versus 16 patients in the standard-treatment arm [9]. Therefore, SPRINT was not adequately powered to detect the kidney protective effects of intensive BP-lowering.

Iako je SPRINT pokazao znatnu kardioprotektivnu korist kada je sistolički krvni tlak bio ciljan na razine<120 mmHg compared with <140 mmHg, the 2017 AHA/ ACC guideline set the systolic BP target at 130 mmHg [1]. Most likely, this algebraic adjustment by 10 mmHg was performed in an attempt to counteract the expected mean difference between routine office BP recordings that are widely used in daily clinical practice and research-grade BP measurement methodology that guided the intensifies- cation of antihypertensive treatment throughout the SPRINT trial. In SPRINT, office BP was measured under standardized conditions: multiple automated BP recordings were taken after a prespecified 5-minute rest period in a quiet room and without the presence of an observer in the room [8]. In a diagnostic test study that included 275 patients with CKD, office BP was measured with the research-grade technique that was used in SPRINT [11]. On the same day, office BP was also recorded without the specification of a 5-minute seated rest [11]. The mean difference between research-grade and routine office systolic BP was −12.7 mmHg, but the 95% limits of agreement were wide, ranging from −46.1 mmHg to 20.7 mmHg [11]. These data indicate that algebraic manipulation of routine office BP of any degree is probably insufficient to counteract the large variability in BP levels from patient to patient. Perhaps the 2021 KDIGO guidelines take a clearer and more straightforward position on this crucial issue, recommending a systolic BP target of <120 mmHg (as in the intensive-treatment arm of SPRINT) with the use of standardized BP measurement methodology in the office environment [2].

Have the results of SPRINT conclusively answered the question of the optimal BP target for the management of hypertension in the entire spectrum of patients with CKD? The answer is probably no. The results of SPRINT are generalizable to patients with clinical characteristics similar to those of the patients who participated in that landmark trial. Notably, SPRINT excluded patients with diabetic kidney disease, polycystic kidney disease, proteinuria >1 g/ dan, i eGFR<20 ml/min/1.73 m2 [8–10]. Future research is needed to investigate the benefit/risk ratio of intensive BP-lowering protocols in these large subgroups of patients with CKD.

Usklađenost s etičkim standardima

Reference

1. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison HC, et al. 2017. ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Smjernice za prevenciju, otkrivanje, procjenu i upravljanje visokim krvnim tlakom u odraslih: Izvješće Američkog koledža za kardiologiju/American Radna skupina Heart Association za smjernice kliničke prakse. Hipertenzija 2018;71:1269–324.

2. KDIGO 2021 Smjernice kliničke prakse za upravljanje krvnim tlakom kod kronične bubrežne bolesti. Kidney Int. 2021.; 99: S1-S87.

3. Suzuki Y, Kaneko H, Yano Y, Okada A, Fujio K, Matsuoka S, et al. Povezanost krvnog tlaka s kardiovaskularnim ishodima u bolesnika s mjernom trakom proteinurije i očuvanom funkcijom bubrega. Hypertens Res. 2022.

4. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, et al. Učinci restrikcije proteina u prehrani i kontrole krvnog tlaka na progresiju kronične bubrežne bolesti. Modifikacija prehrane u skupini za proučavanje bolesti bubrega. N. Engl J Med. 1994; 330: 877–84.

5. Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Učinak snižavanja krvnog tlaka i klase antihipertenzivnih lijekova na progresiju hipertenzivne bolesti bubrega: rezultati ispitivanja AASK. JAMA 2002;288:2421–31.

6. Appel LJ, Wright JT, Greene T, Agodoa LY, Astor BC, Bakris GL, et al. Intenzivna kontrola krvnog tlaka u hipertenzivnoj kroničnoj bubrežnoj bolesti. N. Engl J Med. 2010;363:918-29.

7. Bolesti bubrega: Radna skupina za poboljšanje globalnih ishoda (KDIGO) za krvni tlak. KDIGO smjernice kliničke prakse za upravljanje krvnim tlakom u kroničnoj bubrežnoj bolesti. Kidney Int Suppl. 2012;2:337-414.

8. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. Randomizirano ispitivanje intenzivne i standardne kontrole krvnog tlaka. N. Engl J Med. 2015;373:2103-16.

9. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Učinci intenzivne kontrole AT u CKD. J Am Soc Nephrol. 2017;28:2812-23.

10. Chang AR, Kramer H, Wei G, Boucher R, Grams ME, Berlowitz D, et al. Učinci intenzivne kontrole krvnog tlaka u pacijenata sa i bez albuminurije: Post hoc analize iz SPRINT-a. Clin J Am Soc Nephrol. 2020;15:1121–8.

11. Agarwal R. Implikacije tehnike mjerenja krvnog tlaka za provedbu ispitivanja sistoličkog krvnog tlaka (SPRINT). J Am Heart Assoc. 2017;6:e004536.

Za više informacija: david.deng@wecistanche.com WhatApp:86 13632399501