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BP cilja ● hroničnu bolest bubrega ● hipertenziju

I dalje se raspravlja o ciljevima optimalnog krvnog tlaka (BP) za pacijente s hipertenzijom i kroničnom bubrežnom bolešću (CKD). Smjernice American Heart Association/American College of Cardiology (AHA/ACC) iz 2017. modificirale su definiciju/klasifikaciju hipertenzije i uvele intenzivan cilj za krvni 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, cistanche je tradicionalna kineska biljka koja se vekovima koristi za lečenje raznih bolesti. Naučno je dokazano da ima antiinflamatorna, anti-aging i antioksidativna svojstva. Istraživanja su pokazala da je cistanche koristan za pacijente koji pate od bolesti bubrega. Poznato je da aktivni sastojci cistanchea smanjuju upalu, poboljšavaju funkciju bubrega i obnavljaju oštećene bubrežne stanice. Stoga, integracija cistanchea u plan liječenja bolesti bubrega može ponuditi velike prednosti pacijentima u upravljanju njihovim stanjem. Cistanche pomaže u smanjenju proteinurije, snižava nivoe BUN-a i kreatinina i smanjuje rizik od daljnjeg oštećenja bubrega. Osim toga, cistanche također pomaže u smanjenju razine kolesterola i triglicerida koji mogu biti opasni za pacijente koji pate od bolesti bubrega.

Kliknite na Cistanche Tubulosa za bolest 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 definisanju hipertenzije i identifikaciji optimalnih terapijskih ciljeva je procena nivoa krvnog pritiska u vezi sa rizikom od štetnih zdravstvenih ishoda, kao što je urađeno u velikoj opservacionoj studiji Suzuki et al. [3]. Među pojedincima koji uzimaju lijekove za snižavanje krvnog tlaka, ova analiza je pokazala da kategorija stadijuma 1 hipertenzije, kako je definirano u smjernicama AHA/ACC iz 2017., ne identificira pacijente s većim rizikom od razvoja kardiovaskularnih bolesti [3]. Ako pretpostavimo da je ova povezanost rizika uzročna, onda cilj intenzivnog krvnog tlaka od 130/80 mmHg koji je utvrđen u smjernicama AHA/ACC iz 2017. možda neće biti prikladan za liječenje hipertenzije kod pacijenata s proteinurskom CKD. Uzimajući u obzir da je inherentno ograničenje opservacijskih studija njihova nesposobnost da pruže direktne uzročno-posljedične asocijacije na rizik, pouzdaniji pristup za definiranje praga terapeutske koristi krvnog tlaka je procjena podataka iz randomiziranih studija koje pokazuju smanjenje rizika od štetne zdravstvene ishode sa intenzivnim protokolima za snižavanje krvnog pritiska.

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 modifikuje efekte tretmana intenzivnog snižavanja krvnog pritiska takođe je podržana post hoc analizom AASK-a [6]. Nakon završetka faze ispitivanja, učesnici AASK-a su pozvani da učestvuju u kohortnoj studiji nakon ispitivanja. U ukupnoj analizi i probne i kohortne faze AASK-a, nije bilo razlike između grupe intenzivnog i standardnog liječenja u riziku od progresije CKD [6]. Međutim, uočeno je značajno smanjenje relativnog rizika od 27 posto u kompozitnom ishodu bubrega u podgrupi učesnika AASK-a koji su imali omjer proteina i kreatinina u urinu > 0.22 g/g na početku [6]. Iako je indikacija nefroprotekcije uz intenzivnu kontrolu krvnog pritiska primijećena samo u analizama podgrupa, ovi podaci niskog kvaliteta utjecali su na smjernicu KDIGO iz 2012. da pruži slabu 2D preporuku za stroži cilj BP-a<130/80 mmHg in proteinuric CKD and a standard BP target of <140/90 mmHg for patients without proteinuric CKD [7].

Objavljeno 2015. godine, ispitivanje intervencije sistoličkog krvnog pritiska (SPRINT) pokazalo je da među 9361 nedijabetičara sa visokim kardiovaskularnim rizičnim profilom, cilja na sistolni krvni pritisak 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 značajnu kardioprotektivnu korist kada je sistolni krvni pritisak bio ciljan na nivoe<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 sa 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 Smjernica za prevenciju, otkrivanje, evaluaciju i upravljanje visokim krvnim tlakom kod odraslih: Izvještaj Američkog kardiološkog koledža/ American Radna grupa udruženja za srce za smjernice za kliničku praksu. Hypertension 2018;71:1269–324.

2. KDIGO 2021 Vodič za kliničku praksu za upravljanje krvnim pritiskom kod hronične 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 kod pacijenata s proteinurijom i očuvanom funkcijom bubrega. Hypertens Res. 2022.

4. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, et al. Efekti ograničenja proteina u ishrani i kontrole krvnog pritiska na napredovanje hronične bubrežne bolesti. Modifikacija ishrane u studijskoj grupi za bubrežne bolesti. 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 antihipertenziva 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 pritiska kod hipertenzivne hronične bolesti bubrega. N. Engl J Med. 2010;363:918–29.

7. Bolest bubrega: Poboljšanje globalnih ishoda (KDIGO) Radna grupa za krvni pritisak. KDIGO vodič za kliničku praksu za zbrinjavanje krvnog tlaka kod kronične bubrežne bolesti. Kidney Int Suppl. 2012;2:337–414.

8. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. Nasumično ispitivanje intenzivne u odnosu na standardnu ​​kontrolu krvnog pritiska. N. Engl J Med. 2015;373:2103–16.

9. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Efekti intenzivne kontrole krvnog pritiska 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. Efekti intenzivne kontrole krvnog pritiska kod 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 intervencije sistolnog krvnog tlaka (SPRINT). J Am Heart doc. 2017;6:e004536.

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