diuretics

利尿剂
  • 文章类型: Journal Article
    Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age ± standard deviation 81.9 ± 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.
    UNASSIGNED: Die Hyponatriämie ist die häufigste Elektrolytstörung in der geriatrischen Medizin. Mögliche Ursachen der Hyponatriämie wurden retrospektiv bei allen stationären Patienten im Jahr 2016 evaluiert (N = 2267 [1564 Frauen, 703 Männer], Alter 81,9 ± 7,6 Jahre [Mittelwert ± Standardabweichung]). Irgendeine Form der Hyponatriämie bei Krankenhausaufnahme, während des Aufenthalts oder bei Entlassung wurde bei 308 Patienten (13,6 % [231 Frauen, 77 Männer; Durchschnittsalter ± Standardabweichung 83,1 ± 7,3; p = 0,009 im Vergleich zum Alter aller Patienten]) festgestellt. Die Wahrscheinlichkeit, eine Hyponatriämie zu entwickeln, lag bei Frauen höher als bei Männern (p = 0,019). 131 Patienten waren hypovolämisch, und bei 71 Patienten war eine Dyspnoe als Hinweis für eine Hypervolämie dokumentiert. Nur 12 Patienten mit einer Hyponatriämie (3,9 %) erhielten keines der ausgewerteten, potenziell die Plasma-Natrium-Konzentration senkenden Medikamente (Diuretika, Angiotensin-Converting-Enzyme-Inhibitoren, Angiotensin-II-Rezeptor-Antagonisten, Antidepressiva, Neuroleptika, nichtsteroidale Antirheumatika, Carbamazepin, Oxcarbazepin). Im Median lag die Zahl der potenziell den Plasma-Natrium-Spiegel senkenden Medikamente pro Patient bei 3, die höchste Zahl war 7. Hypovolämische Hyponatriämie und das Syndrom der inadäquaten ADH-Sekretion waren die wichtigsten Ursachen einer Hyponatriämie. Beide Zustände wurden am häufigsten durch unerwünschte Medikamentenwirkungen ausgelöst. Patienten mit Hyponatriämie sollten möglichst wenige Medikamente erhalten, die den Plasma-Natrium-Spiegel senken können. Thiaziddiuretika sollten vollständig vermieden werden, und ältere Personen sollten mit der Nahrung ausreichend Salz zu sich nehmen.
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  • 文章类型: Journal Article
    Na+-Cl-协同转运蛋白(NCC)驱动肾脏中的盐再吸收,并在平衡电解质和血压中起决定性作用。噻嗪类和噻嗪类利尿剂抑制NCC介导的肾盐潴留,自1950年代以来一直是治疗高血压和水肿的基石。在这里,我们确定与噻嗪类药物氢氯噻嗪单独复合的NCC共结构,还有两种噻嗪类药物氯噻酮和茚达帕胺,揭示它们适合正位位点并阻塞NCC离子易位途径。WNKs-SPAK激酶级联异常激活NCC是家族性高钾血症高血压的基础,但目前尚不清楚磷酸化是否/如何改变NCC结构以加速离子易位。我们显示NCC的细胞内氨基末端基序,一旦磷酸化,与羧基末端结构域相关,一起,它们与跨膜结构域相互作用。这些相互作用表明磷酸化依赖性变构网络直接影响NCC离子易位。
    The Na+-Cl- cotransporter (NCC) drives salt reabsorption in the kidney and plays a decisive role in balancing electrolytes and blood pressure. Thiazide and thiazide-like diuretics inhibit NCC-mediated renal salt retention and have been cornerstones for treating hypertension and edema since the 1950s. Here we determine NCC co-structures individually complexed with the thiazide drug hydrochlorothiazide, and two thiazide-like drugs chlorthalidone and indapamide, revealing that they fit into an orthosteric site and occlude the NCC ion translocation pathway. Aberrant NCC activation by the WNKs-SPAK kinase cascade underlies Familial Hyperkalemic Hypertension, but it remains unknown whether/how phosphorylation transforms the NCC structure to accelerate ion translocation. We show that an intracellular amino-terminal motif of NCC, once phosphorylated, associates with the carboxyl-terminal domain, and together, they interact with the transmembrane domain. These interactions suggest a phosphorylation-dependent allosteric network that directly influences NCC ion translocation.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    目的:在急性失代偿性心力衰竭(ADHF)患者中,由于缺乏有效剂量的利尿剂滴定而导致的充血不完全是再入院的常见原因。利钠反应预测方程(NRPE)是一种新颖的工具,被证明可以快速准确地预测利钠反应,并且不需要尿液收集。然而,NRPE尚未经过外部验证。这项研究的目的是从外部验证NRPE在ADHF和液体超负荷患者中的辨别能力。
    结果:纳入需要静脉环利尿剂的ADHF患者。利尿剂给药后约2小时获得斑点尿样,并由研究人员定时收集6小时的尿液。使用NRPE使用斑点尿样中的尿钠和尿肌酐来预测6小时利钠反应。主要目标是验证NRPE以区分利尿剂利钠反应不良(利尿剂给药后6小时钠输出量<50mmol)。将NRPE与尿钠进行比较,并测量尿量,这是国际指南目前推荐的评估利尿剂反应的方法。分析了49例患者的87例利尿剂给药。患者的平均年龄为57±17岁,67%为男性。平均估计肾小球滤过率为65±28mL/min/1.73m2,射血分数为35±15%。在研究当天给予的静脉内呋塞米等同物的中位剂量为80mg(IQR40-160)。在39%的访视中出现了不良的利钠反应。NRPE在6小时尿液收集过程中预测不良利钠反应的AUC为0.91(95%CI0.85-0.98)。与NRPE相比,点尿钠浓度(AUC0.75)和相应护理班次期间的尿量(AUC0.74)显示出较低的辨别能力。
    结论:在这个ADHF患者队列中,NRPE优于点尿钠浓度和与利尿剂反应相关的所有其他指标,以预测不良的利尿剂反应.我们的发现支持在其他设置中使用该方程,以快速准确地预测利钠反应。
    OBJECTIVE: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload.
    RESULTS: Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6-h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6-h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output <50 mmol in the 6 h following diuretic administration). The NRPE was compared with urine sodium and measured urine output which are the methods currently recommended by international guidelines to assess diuretic response. Eighty-seven diuretic administrations from 49 patients were analysed. Mean age of patients was 57 ± 17 years and 67% were male. Mean estimated glomerular filtration rate was 65 ± 28 mL/min/1.73 m2, and ejection fraction was 35 ± 15%. Median dose of intravenous furosemide equivalents administered the day of the study was 80 mg (IQR 40 - 160). Poor natriuretic response occurred in 39% of the visits. The AUC of the NRPE to predict poor natriuretic response during the 6-h urine collection was 0.91 (95% CI 0.85-0.98). Compared with the NRPE, spot urine sodium concentration (AUC 0.75) and urine output during the corresponding nursing shift (AUC 0.74) showed lower discrimination capacity.
    CONCLUSIONS: In this cohort of patients with ADHF, the NRPE outperformed spot urine sodium concentration and all other metrics related to diuretic response to predict poor natriuretic response. Our findings support the use of this equation at other settings to allow rapid and accurate prediction of natriuretic response.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    在这次系统审查中,我们报道了与持续使用利尿剂相比,使用利尿剂的效果.我们纳入了报告死亡率等结果的临床研究,心力衰竭复发,耐受性和可行性。我们使用GRADE框架评估了证据的偏倚和确定性风险。我们纳入了来自22项主要研究的25篇出版物(15项随机对照试验;7项非随机研究)。取消处方组的平均参与者人数为35,中位数/平均年龄为64岁。心力衰竭患者,没有明确证据表明,与继续服用利尿剂相比,服用利尿剂与死亡率增加相关(低确定性证据).与利尿剂去处方相关的心血管复合结局的风险不一致(研究显示利尿剂去处方的风险较低,或与利尿剂持续相当的风险;非常低的确定性证据)。利尿剂对心力衰竭患者服用利尿剂后心力衰竭复发的影响,在纳入的研究中,使用利尿剂治疗高血压的患者的高血压比例不一致(低确定性证据).在利尿剂治疗高血压的患者中,利尿剂去处方耐受性良好(中度确定性证据),而在使用利尿剂治疗心力衰竭的患者中,停用利尿剂可导致外周水肿的主诉(确定性非常低的证据)。总体偏倚风险普遍较高。总之,本系统综述提示,对于精心挑选的患者,停用利尿剂可能是一种安全可行的治疗选择.然而,缺乏关于其可行性的高质量证据,利尿剂处方的安全性和耐受性,保证进一步的研究。
    In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.
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  • 文章类型: English Abstract
    肾功能衰竭是常见的,并且在老年患者中患病率急剧增加。它是多发性疾病的常见方面,并与多药效有关。根据现有文献,概述了重要的药物-药物相互作用以及如何避免或管理它们。在各种可能的相互作用中,抗凝和利尿剂治疗仍然代表着最高的临床相关性。
    Renal failure is common and comes with a steep increasing prevalence in older patients. It is a frequent aspect in multimorbidity and associated with polypharmacia. Based on available literature an overview is given concerning important drug-drug interactions and how to avoid or manage them. Among a large variety of possible interactions anticoagulation and diuretic therapy still represent the highest clinical relevance.
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  • 文章类型: Journal Article
    目的:充血与心脏甲状腺素运载蛋白淀粉样变性(ATTR-CA)预后相关,但是拥堵是否具有超出既定范围的增量预测价值,拥塞敏感性NT-proBNP未知.因此,我们的目的是比较评估几种充血替代NT-proBNP的预后效用。
    方法:我们从局部淀粉样变性队列研究AmyKoS的面板数据集中,通过具有时变协变量的Cox比例风险回归估计了风险比。通过使用chi(χ)2统计量测量总体模型显著性来比较不同的模型。
    结论:131例ATTR-CA患者(野生型84.0%,遗传性6.9%,无基因检测9.2%;中位年龄78.7岁(四分位数73.3,82.1岁;男性85.5%),中位随访38.2个月(30.6;48.2个月),共566次观察被分析.83.2%接受了疾病改善治疗;20.6%同时参加了安慰剂对照的基因沉默试验。关于阻塞的信息改善了生物标志物驱动的风险分层,并确定了风险最高的患者。超声心动图充血标志物的表现优于临床表现和每日利尿剂使用/剂量。相关调节剂为每日利尿剂用量,疾病改善治疗,eGFR,和右心房容积。NT-proBNP和三尖瓣反流峰值速度(tr-vmax)提供了易于使用的分层,其整体模型性能类似于NAC和Mayo分期系统。进一步的分析对于验证和确定拥塞标记的最佳切点是必要的。
    OBJECTIVE: Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP.
    METHODS: We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance.
    CONCLUSIONS: 131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.
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  • 文章类型: Journal Article
    尽管社区获得性急性肾损伤(CA-AKI)占所有AKI发病率的重要子集,由于诊断前缺乏全面的数据,证据有限.这里,我们使用详尽的诊断前处方数据检查了CA-AKI的用药风险.我们包括78,754名工作年龄的健康人,他们接受了年度健康检查计划。我们进行了一项队列研究,使用Cox比例风险模型评估流行药物使用与随后的CA-AKI发生率之间的关联。随后,我们进行了一项病例交叉研究,使用条件泊松回归模型比较了CA-AKI发病前的病例期(-3~0个月)和CA-AKI发病前的对照期(-15~-12个月和-9~-6个月)的新药使用情况.肾素-血管紧张素-醛固酮系统(RAAS)抑制剂的普遍使用与CA-AKI发病率增加有关。但新的用途不是。利尿剂的新用途,抗感染药物,和造影剂也与CA-AKI发病率增加相关.这些结果表明,我们需要注意服用这些常用药物的普通人群中AKI的发生率。
    Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs.
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  • 文章类型: Case Reports
    氢氯噻嗪是一种常用于治疗高血压的利尿剂,充血性心力衰竭或肝硬化引起的慢性水肿,和肾性尿崩症。利尿剂通过增加尿量起作用,并根据其作用的特定肾段进行分类。和所有的药物一样,他们并非没有副作用。最显著和最严重的包括低血容量和电解质紊乱。其他更罕见的不良反应包括皮炎和超敏反应。我们讨论了一名86岁的男性,他出现在急诊室,抱怨头昏眼花和进行性剥脱性皮疹,这是在门诊开始氢氯噻嗪后不久开始的。
    Hydrochlorothiazide is a diuretic agent commonly used to treat hypertension, chronic edema from congestive heart failure or cirrhosis, and nephrogenic diabetes insipidus. Diuretics work by increasing urine output and are classified based on the specific renal segments they act on. As with all medications, they are not without their side effects. The most significant and serious include hypovolemia and electrolyte disturbances. Other more rare adverse effects include dermatitis and hypersensitivity reactions. We discuss an 86-year-old male who presented to the emergency room with complaints of lightheadedness and progressive exfoliating rash that began shortly after starting hydrochlorothiazide in an outpatient setting.
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