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BP eesmärgid●krooniline neeruhaigus●hüpertensioon

Jätkuvalt arutatakse hüpertensiooni ja kroonilise neeruhaigusega (CKD) patsientide optimaalse vererõhu (BP) eesmärkide üle. 2017. aasta American Heart Association / American College of Cardiology (AHA/ACC) juhised muutsid hüpertensiooni määratlust/klassifikatsiooni ja kehtestasid intensiivse vererõhu eesmärgi<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?

Asjakohaste uuringute kohaselt on tsistanche traditsiooniline Hiina ravimtaim, mida on sajandeid kasutatud erinevate haiguste raviks. Teaduslikult on tõestatud, et sellel on põletikuvastased, vananemisvastased ja antioksüdantsed omadused. Uuringud on näidanud, et tsistanche on kasulik neeruhaigusega patsientidele. Tistanche toimeained vähendavad teadaolevalt põletikku, parandavad neerufunktsiooni ja taastavad kahjustatud neerurakke. Seega võib cistanche'i integreerimine neeruhaiguste raviplaani pakkuda patsientidele oma seisundi juhtimisel suurt kasu. Cistanche aitab vähendada proteinuuriat, alandab BUN-i ja kreatiniini taset ning vähendab edasise neerukahjustuse riski. Lisaks aitab tsistanche vähendada kolesterooli ja triglütseriidide taset, mis võib olla ohtlik neeruhaigusega patsientidele.

Neeruhaiguse jaoks klõpsake valikul Cistanche Tubulosa

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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].

Üks lähenemisviis hüpertensiooni määratlemiseks ja optimaalsete terapeutiliste sihtmärkide kindlakstegemiseks on hinnata BP taset kahjulike tervisemõjude riski kohta, nagu tehti Suzuki jt suures vaatlusuuringus. [3]. Vererõhu taset alandavaid ravimeid kasutavate inimeste seas näitas see analüüs, et 1. staadiumi hüpertensiooni kategooria, nagu on määratletud 2017. aasta AHA/ACC juhistes, ei tuvasta patsiente, kellel on suurem risk haigestuda südame-veresoonkonna haigustesse [3]. Kui eeldame, et see riskiseos on põhjuslik, siis 2017. aasta AHA/ACC juhendis kehtestatud intensiivne BP eesmärk 130/80 mmHg ei pruugi sobida proteinuurilise kroonilise neeruhaigusega patsientide hüpertensiooni raviks. Võttes arvesse, et vaatlusuuringute olemuslik piirang on nende suutmatus luua otseseid põhjuse ja tagajärje riski seoseid, on usaldusväärsem lähenemisviis terapeutilise kasu BP läve määratlemiseks randomiseeritud uuringute andmete hindamine, mis näitavad haigestumise riski vähenemist. ebasoodsad tervisemõjud intensiivsete BP-d langetavate protokollidega.

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/päevas) algtasemel [4]. Arvamust, et proteinuuria muudab intensiivse BP-langetamise raviefekte, toetas ka AASK-i post hoc analüüs [6]. Pärast katsefaasi lõpetamist kutsuti AASK osalejad osalema katsejärgses kohortuuringus. AASK nii katse- kui ka kohortfaasi üldises analüüsis ei ilmnenud kroonilise neeruhaiguse progresseerumise riski osas intensiivravi ja standardravi rühmas erinevust [6]. Siiski täheldati olulist 27-protsendilist suhtelise riski vähenemist liitneerutulemuses AASK-s osalejate alarühmas, kelle uriini valgu ja kreatiniini suhe oli algtasemel > 0,22 g/g [6]. Ehkki intensiivse vererõhu kontrolliga nefroprotektsiooni viidet täheldati ainult alarühmade analüüsides, mõjutasid need madala kvaliteediga andmed KDIGO 2012. aasta juhist, andes nõrga 2D taseme soovituse rangema BP eesmärgi saavutamiseks.<130/80 mmHg in proteinuric CKD and a standard BP target of <140/90 mmHg for patients without proteinuric CKD [7].

2015. aastal avaldatud süstoolse vererõhu sekkumise uuring (SPRINT) näitas, et 9361 kõrge kardiovaskulaarse riskiprofiiliga mittediabeetilise patsiendi hulgas oli süstoolne vererõhk<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.

Kuigi SPRINT näitas olulist kardioprotektiivset kasu, kui süstoolne BP oli suunatud tasemele<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 päevas ja 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.

Eetiliste standardite järgimine

Viited

1. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison HC jt. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA juhised kõrge vererõhu ennetamiseks, tuvastamiseks, hindamiseks ja juhtimiseks täiskasvanutel: Ameerika Kardioloogiakolledži aruanne/ American Südameassotsiatsiooni kliiniliste tavade juhiste töörühm. Hüpertensioon 2018; 71:1269–324.

2. KDIGO 2021. aasta kliinilise praktika juhised vererõhu juhtimiseks kroonilise neeruhaiguse korral. Kidney Int. 2021; 99:S1–S87.

3. Suzuki Y, Kaneko H, Yano Y, Okada A, Fujio K, Matsuoka S jt. Vererõhu seos kardiovaskulaarsete tulemustega patsientidel, kellel on mõõtevarraste proteinuuria ja säilinud neerufunktsioon. Hypertens Res. 2022. aasta.

4. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW jt. Toiduvalkude piiramise ja vererõhu kontrolli mõju kroonilise neeruhaiguse progresseerumisele. Dieedi muutmine neeruhaiguste uurimisrühmas. N. Engl J Med. 1994; 330: 877–84.

5. Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J jt. Vererõhu langetamise ja antihüpertensiivsete ravimite klassi mõju hüpertensiivse neeruhaiguse progresseerumisele: AASK uuringu tulemused. JAMA 2002;288:2421–31.

6. Appel LJ, Wright JT, Greene T, Agodoa LY, Astor BC, Bakris GL jt. Intensiivne vererõhu kontroll hüpertensiivse kroonilise neeruhaiguse korral. N. Engl J Med. 2010;363:918–29.

7. Neeruhaigus: globaalsete tulemuste parandamine (KDIGO) vererõhu töörühm. KDIGO kliinilise praktika juhend vererõhu juhtimiseks kroonilise neeruhaiguse korral. Kidney Int Suppl. 2012;2:337–414.

8. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV jt. Randomiseeritud uuring intensiivse ja standardse vererõhu kontrolli kohta. N. Engl J Med. 2015;373:2103–16.

9. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL jt. Intensiivse BP kontrolli mõju kroonilise neeruhaiguse korral. J Am Soc Nephrol. 2017;28:2812–23.

10. Chang AR, Kramer H, Wei G, Boucher R, Grams ME, Berlowitz D jt. Intensiivse vererõhu kontrolli mõju albuminuuriaga ja ilma selleta patsientidel: SPRINTi post hoc analüüsid. Clin J Am Soc Nephrol. 2020;15:1121–8.

11. Agarwal R. Vererõhu mõõtmise tehnika mõju süstoolse vererõhu sekkumisuuringu (SPRINT) rakendamiseks. J Am Heart Assoc. 2017;6:e004536.

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