MRA, mineralocorticoid receptor antagonist

MRA,盐皮质激素受体拮抗剂
  • 文章类型: Journal Article
    慢性肾脏病(CKD)是2型糖尿病(T2DM)最常见的并发症之一,也是心血管疾病的独立危险因素。盐皮质激素受体(MR)是在许多组织类型中表达的核受体,包括肾脏和心脏.醛固酮对T2DM患者的MR异常和长期激活会引发不利影响(例如,炎症和纤维化)在这些组织中。在T2DM早期抑制醛固酮已成为T2DM相关CKD患者的治疗策略。尽管患者已经接受肾素-血管紧张素系统(RAS)阻滞剂治疗数十年,单独的RAS阻断剂不足以预防CKD进展。类固醇MR拮抗剂(MRAs)已与RAS阻滞剂联合使用;然而,不希望的不利影响限制了它们的使用,促使开发具有更好目标特异性和安全性的非甾体MRA。最近进行的研究,Finenerone减少糖尿病肾病的肾衰竭和疾病进展(FIDELIO-DKD)和Finenerone减少糖尿病肾病的心血管死亡率和发病率(FIGARO-DKD),已经报告了Finerenone,非甾体MRA,与安慰剂相比,改善肾脏和心血管结局.在这篇文章中,我们回顾了MRA的发展历史,并讨论了其与其他治疗方案相结合的可能性,如钠-葡萄糖协同转运蛋白2抑制剂,胰高血糖素样肽-1受体激动剂,和2型糖尿病相关CKD患者的钾结合剂。
    Chronic kidney disease (CKD) is one of the most frequent complications associated with type 2 diabetes mellitus (T2DM) and is also an independent risk factor for cardiovascular disease. The mineralocorticoid receptor (MR) is a nuclear receptor expressed in many tissue types, including kidney and heart. Aberrant and long-term activation of MR by aldosterone in patients with T2DM triggers detrimental effects (eg, inflammation and fibrosis) in these tissues. The suppression of aldosterone at the early stage of T2DM has been a therapeutic strategy for patients with T2DM-associated CKD. Although patients have been treated with renin-angiotensin system (RAS) blockers for decades, RAS blockers alone are not sufficient to prevent CKD progression. Steroidal MR antagonists (MRAs) have been used in combination with RAS blockers; however, undesired adverse effects have restricted their usage, prompting the development of nonsteroidal MRAs with better target specificity and safety profiles. Recently conducted studies, Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), have reported that finerenone, a nonsteroidal MRA, improves both renal and cardiovascular outcomes compared with placebo. In this article, we review the history of MRA development and discuss the possibility of its combination with other treatment options, such as sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and potassium binders for patients with T2DM-associated CKD.
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  • 文章类型: Journal Article
    心脏毒性是传统和靶向癌症疗法的相对频繁且潜在严重的副作用。已在随机对照试验中测试了一般措施和特定的药物心脏保护干预措施以及基于成像和生物标志物的监测策略以识别高风险患者,以预防或减轻癌症治疗相关的心脏毒性作用。尽管包括早期试验在内的荟萃分析显示了总体有益的效果,结果存在很大的异质性。最近在接受蒽环类和/或人类表皮生长因子受体2靶向治疗的患者中神经激素抑制剂的随机对照试验显示,与癌症治疗相关的心功能不全的发生率低于先前报道的,并且干预措施的效果适中或没有持续的效果。缺乏有关新型癌症药物的预防性心脏保护策略的数据。较大,需要对传统和新型干预措施进行前瞻性多中心随机临床试验,以更准确地定义不同心脏保护策略的益处,并改进风险预测和确定可能受益的患者.
    Cardiotoxicity is a relatively frequent and potentially serious side effect of traditional and targeted cancer therapies. Both general measures and specific pharmacologic cardioprotective interventions as well as imaging- and biomarker-based surveillance strategies to identify patients at high risk have been tested in randomized controlled trials to prevent or attenuate cancer therapy-related cardiotoxic effects. Although meta-analyses including early trials suggest an overall beneficial effect, there is substantial heterogeneity in results. Recent randomized controlled trials of neurohormonal inhibitors in patients receiving anthracyclines and/or human epidermal growth factor receptor 2-targeted therapies have shown a lower rate of cancer therapy-related cardiac dysfunction than previously reported and a modest or no sustained effect of the interventions. Data on preventive cardioprotective strategies for novel cancer drugs are lacking. Larger, prospective multicenter randomized clinical trials testing traditional and novel interventions are required to more accurately define the benefit of different cardioprotective strategies and to refine risk prediction and identify patients who are likely to benefit.
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  • 文章类型: Journal Article
    研究慢性肾病患者高钾血症与长期心血管和肾脏预后之间的关系。
    使用日本医院索赔登记处进行了一项观察性回顾性队列研究,医疗数据愿景(2008年4月1日至2018年9月30日)。在1,208,894名患者中,至少有1次钾测量,根据国际疾病分类选择了167,465例慢性肾脏病患者,第十修订代码或估计肾小球滤过率(eGFR)小于60mL/min/1.73m2。高钾血症定义为在12个月内至少2次钾测量为5.1mmol/L或更高。正常血钾对照组是没有记录钾水平为5.1mmol/L或更高和3.5mmol/L或更低的患者。eGFR和死亡危险比的变化,因心脏事件住院,心力衰竭,在倾向评分匹配的高钾血症患者和正常钾血对照组之间评估了肾脏替代治疗的引入。
    在符合分析条件的16,133名高钾血症患者和11,898名正钾血症对照者中,在倾向评分匹配后,选择了5859例(36.3%)患者和5859例(49.2%)对照。平均随访期为3.5年。患者和对照组的3年eGFR变化分别为-5.75和-1.79mL/min/1.73m2。总的来说,高钾血症患者的死亡风险较高,因心脏事件住院,心力衰竭,和肾脏替代疗法的引入比对照组,风险比为4.40(95%CI,3.74至5.18),1.95(95%CI,1.59至2.39),5.09(95%CI,4.17至6.21),和7.54(95%CI,5.73至9.91),分别。
    高钾血症与死亡和不良临床结局的显著风险相关,肾功能下降更快。这些发现强调了高钾血症作为慢性肾脏病患者未来不良事件的易感性的重要性。
    UNASSIGNED: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease.
    UNASSIGNED: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score-matched hyperkalemic patients and normokalemic controls.
    UNASSIGNED: Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was -5.75 and -1.79 mL/min/1.73 m2, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively.
    UNASSIGNED: Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.
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  • 文章类型: Journal Article
    UNASSIGNED: Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF).
    UNASSIGNED: Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization.
    UNASSIGNED: 1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p < 0.05), multivariate COX model confirmed that anemia was not independently associated with all-cause mortality [hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.85-1.52, p = 0.386] and all-cause re-hospitalization (HR 1.13, 95% CI 0.96-1.33, p = 0.152). Similarly, RD was not an independent predictor of all-cause mortality (HR 1.18, 95% CI 0.88-1.57, p = 0.269) and all-cause re-hospitalization (HR 0.94, 95% CI 0.79-1.12, p = 0.488) as assessed in the adjusted COX regression model. The interaction between RD and anemia on end-points events was also not statistically significant. However, anemia was associated with increased all-cause re-hospitalization in patients with New York Heart Association (NYHA) class III-IV.
    UNASSIGNED: In patients with HFpEF from CN-HF registry, anemia was common, but was not an independent predictor of all-cause mortality and all-cause re-hospitalization, except for the all-cause re-hospitalization in patients with NYHA class III-IV.Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/home; ID: NCT02079428.
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