Nøgleord

BP-mål ●kronisk nyresygdom ●hypertension

De optimale blodtryksmål (BP) for patienter med hypertension og kronisk nyresygdom (CKD) diskuteres fortsat. 2017 American Heart Association/American College of Cardiology (AHA/ACC) retningslinjer ændrede definitionen/klassificeringen af ​​hypertension og introducerede et intensivt BP-mål på<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?

Ifølge relevante undersøgelser er cistanche en traditionel kinesisk urt, der er blevet brugt i århundreder til at behandle forskellige sygdomme. Det er videnskabeligt bevist at besidde anti-inflammatoriske, anti-aging og antioxidante egenskaber. Undersøgelser har vist, at cistanche er gavnligt for patienter, der lider af nyresygdom. De aktive ingredienser i cistanche er kendt for at reducere inflammation, forbedre nyrefunktionen og genoprette svækkede nyreceller. Integrering af cistanche i en nyresygdomsbehandlingsplan kan således give patienterne store fordele ved at håndtere deres tilstand. Cistanche hjælper med at reducere proteinuri, sænker BUN- og kreatininniveauer og mindsker risikoen for yderligere nyreskade. Derudover hjælper cistanche også med at reducere kolesterol- og triglyceridniveauer, hvilket kan være farligt for patienter, der lider af nyresygdom.

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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].

En tilgang til at definere hypertension og identificere de optimale terapeutiske mål er at evaluere BP-niveauer om risikoen for uønskede helbredsudfald, som gjort i den store observationsundersøgelse af Suzuki et al. [3]. Blandt individer, der tager blodtrykssænkende medicin, viste denne analyse, at kategorien af ​​stadium 1 hypertension, som defineret i 2017 AHA/ACC-retningslinjen, ikke identificerer patienter med højere risiko for at udvikle kardiovaskulær sygdom [3]. Hvis vi antager, at denne risikosammenhæng er kausal, så er det intensive BP-mål på 130/80 mmHg, der blev etableret i 2017 AHA/ACC-retningslinjen, muligvis ikke egnet til behandling af hypertension hos patienter med proteinurisk CKD. I betragtning af, at en iboende begrænsning af observationsstudier er deres manglende evne til at give direkte årsag-og-virkning risikosammenslutninger, er en mere pålidelig tilgang til at definere BP-tærsklen for terapeutisk fordel evalueringen af ​​data fra randomiserede forsøg, der viser reduktioner i risikoen for ugunstige helbredsudfald med intensive BP-sænkende protokoller.

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/dag) ved baseline [4]. Forestillingen om, at proteinuri modificerer behandlingseffekterne af intensiv BP-sænkning, blev også understøttet af en post hoc-analyse af AASK [6]. Efter afslutningen af ​​forsøgsfasen blev AASK-deltagere inviteret til at deltage i et post-trial kohortestudie. I den overordnede analyse af både forsøgs- og kohortefaser af AASK var der ingen forskel mellem intensivbehandlings- og standardbehandlingsarmene i risikoen for progression af CKD [6]. Der blev dog observeret en signifikant 27 procent relativ risikoreduktion i det sammensatte nyreudfald i undergruppen af ​​AASK-deltagere, som havde et urinprotein-til-kreatinin-forhold på > 0,22 g/g ved baseline [6]. Selvom en indikation af nefrobeskyttelse med intensiv BP-kontrol kun blev observeret i undergruppeanalyser, påvirkede disse data af lav kvalitet 2012 KDIGO-retningslinjen til at give en svag niveau 2D-anbefaling for et strammere BP-mål på<130/80 mmHg in proteinuric CKD and a standard BP target of <140/90 mmHg for patients without proteinuric CKD [7].

Udgivet i 2015 viste Systolic Blood Pressure Intervention Trial (SPRINT) at blandt 9361 ikke-diabetiske patienter med en høj kardiovaskulær risikoprofil målrettet mod et systolisk BP på<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.

Selvom SPRINT viste en væsentlig kardiobeskyttende fordel, når systolisk BP blev målrettet til niveauer<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/dag og 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.

Overholdelse af etiske standarder

Referencer

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-retningslinje for forebyggelse, påvisning, evaluering og håndtering af højt blodtryk hos voksne: En rapport fra American College of Cardiology/ American Heart Association Task Force om retningslinjer for klinisk praksis. Hypertension 2018;71:1269–324.

2. KDIGO 2021 kliniske retningslinjer for håndtering af blodtryk ved kronisk nyresygdom. Nyre Int. 2021; 99:S1–S87.

3. Suzuki Y, Kaneko H, Yano Y, Okada A, Fujio K, Matsuoka S, et al. Sammenhængen af ​​BP med kardiovaskulære resultater hos patienter med dipstick-proteinuri og bevaret nyrefunktion. Hypertens Res. 2022.

4. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, et al. Virkningerne af diætproteinrestriktion og blodtrykskontrol på progressionen af ​​kronisk nyresygdom. Ændring af diæt i undersøgelsesgruppen for nyresygdom. N. Engl J Med. 1994; 330: 877-84.

5. Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Effekt af blodtrykssænkende og antihypertensiv lægemiddelklasse på progression af hypertensiv nyresygdom: resultater fra AASK-studiet. JAMA 2002;288:2421-31.

6. Appel LJ, Wright JT, Greene T, Agodoa LY, Astor BC, Bakris GL, et al. Intensiv blodtrykskontrol ved hypertensiv kronisk nyresygdom. N. Engl J Med. 2010;363:918–29.

7. Nyresygdom: Forbedring af globale resultater (KDIGO) Blood Pressure Work Group. KDIGO kliniske retningslinjer for håndtering af blodtryk ved kronisk nyresygdom. Nyre Int Suppl. 2012;2:337-414.

8. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. Et randomiseret forsøg med intensiv versus standard blodtrykskontrol. N. Engl J Med. 2015;373:2103-16.

9. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Effekter af intensiv BP-kontrol ved CKD. J Am Soc Nephrol. 2017;28:2812-23.

10. Chang AR, Kramer H, Wei G, Boucher R, Grams ME, Berlowitz D, et al. Effekter af intensiv blodtrykskontrol hos patienter med og uden Albuminuri: Post Hoc-analyser fra SPRINT. Clin J Am Soc Nephrol. 2020;15:1121-8.

11. Agarwal R. Implikationer af blodtryksmålingsteknik for implementering af systolisk blodtryksinterventionsforsøg (SPRINT). J Am Heart Assoc. 2017;6:e004536.

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