心肾综合症:新概念新进展 Prevention and treatment of Cardio-Renal Syndrome: New Concepts...
-
Upload
vielka-salas -
Category
Documents
-
view
188 -
download
0
description
Transcript of 心肾综合症:新概念新进展 Prevention and treatment of Cardio-Renal Syndrome: New Concepts...
北京世纪坛医院北京大学第九临床医学院
杨水祥
心肾综合症:新概念新进展 Prevention and treatment of
Cardio-Renal Syndrome: New Concepts and Updates
慢性心衰往往被肾功能不全复杂化;急性失代偿性心衰往往因肾功能恶化或利尿剂抵抗预后更差。
心肾综合征( CRS )可能涉及一系列的神经内分泌紊乱及肾稳态调节机制不良。
心肾综合征的发病和治疗需要我们更多的关注。
心肾交互影响
肾功能不全或肾脏疾病已成为慢性心衰或 ADHF预后不良的一个独立预测指标。
左心室功能障碍预防和治疗回顾分析研究( SOLVD )提示,中度肾功能不全(肌酐清除率小于 60 毫升 / 分钟)与心衰住院的全因死亡率和复合终点死亡独立相关,对心衰的严重程度和合并的多元因素调整之后仍然明显相关。
Smith GL 等对 16 项 80000 万例患者评价肾功能不全影响心力衰竭结果的研究进行的荟萃分析表明带给
我们一些启示。
肾功能不全的严重程度与逐步增加的死亡率呈正相关
血肌酐每递增 1 毫克 / 分升则死亡风险增加 33%
肾小球滤过率每递减 10 毫升 / 分钟则死亡风险上升 7 %
CRS 的流行病学
CRS
CRS1 型较常见 在急性失代偿性心衰和急性
冠脉综合征 ( ACS )患者中,急性肾损伤( AKI )的发生率
分别约为24% ~ 45%
和 9% ~ 19%
CRS2 型患者,在ARCSCH 研究中,
随访 9.3 年, 34% 心血管疾病 ( CVD )
患者的肾功能下降[eGFR 下降幅度≥
15 ml/ ( min·1.73m2) ], 其中 5.6% 的患者出现新发肾脏病
CRS3 型的常见原因,包括对比剂所
致急性肾损伤( CI-AKI )、药
物诱导的肾病、心脏及非心
脏大手术后 AKI
等
CRS4 型,美国健康营养调查研究( NHANES Ⅱ )
显示,当患者eGFR≥90 ml/
( min·1.73m2 )、70 ~ 89 ml/ (min·1.73m2 )
和 < 70 ml/ ( min·1.73m2 )
CRS5 型的流行病和病理生理机制研究尚缺乏
CRS1 型较常见,在急性失代偿性心衰和急性冠脉综合征( ACS )患者中,急性肾损伤( AKI )的发生率分别约为 24% ~ 45% 和 9% ~19% 。
CRS2 型患者,在 ARCSCH 研究中,随访 9.3 年,34% 心血管疾病( CVD )患者的肾功能下降[ 肾小球滤过率( eGFR )下降幅度≥ 15 ml/( min·1.73m2 ) ] ,其中 5.6% 的患者出现新发肾脏病。
CRS3 型的常见原因,包括对比剂所致急性肾损伤( CI-AKI )、药物诱导的肾病、心脏及非心脏大手术后 AKI 等。
CRS4 型,美国健康营养调查研究( NHANES Ⅱ )显示,当患者 eGFR≥90 ml/ ( min·1.73m2 )、 70 ~ 89 ml/ ( min·1.73m2 )和 <70 ml/ ( min·1.73m2 )时,其 CVD 的发生率分别为 4.5% 、 7.9% 和 12.9% 。该结果及数项研究提示, CKD 可加速 CVD 的发生风险。
尚缺乏 CRS5 型的流行病和病理生理机制研究。
Figure 1. Cardiorenal interaction and stage classification in the initiation and progression of chronic kidney disease and heart failure
[1] and [11]. CVD, cardiovascular disease; HF, heart failure; GFR, glomerular filtration rate.
Cardiorenal Interaction
SNS激活增加全身血管阻力、儿茶酚胺释放和直接神元刺激,
增加肾脏肾素释放;
可进一步降低压力感受器反射调节的敏感性。
导致血管紧张素Ⅱ释放增多,血管收缩,肾出球小动脉收缩,心脏重塑及醛固酮释放增加,水钠滁留和促进心肌纤维化。
血管紧张素系统激活,血流动力学改变
精氨酸加压素的释放导致血管收缩,水滁留和低钠血症。
心房钠尿肽(心钠素和 B 型利钠肽)释放,健康人钠尿肽可以减轻血管紧张素系统和 SNS激活所致的调节失衡,但心力衰竭时的长期释放可出现钠尿肽抵抗。
肾功能障碍和高血压控制不良也促进醛固酮释放,从而促进心衰发展。
A Prospective, Blinded Study of Bioimpedance Vector Analysis and Biomarker Testing
for the Prediction of Worsening Renal Function in Consecutive Patients with Acutely
Decompensated Heart Failure: Primary Results of the Biomonitoring and Cardiorenal
Syndrome in Heart Failure (BIONICS-HF) Trial
Independent role of high central venous pressure in predicting worsening of renal
function in chronic heart failure outpatients
CRS 的预防
CRS 的预防
CRS 的预防
CRS1 型的预防,首要方法是减轻或避免患者发生 ADHF
和 ACS
CRS1 型的预防,首要方法是减轻或避免患者发生 ADHF
和 ACS
CRS2 型的预防,重要的是通过低钠饮食和使用利尿剂优化钠与细胞外液容量的管
理
CRS2 型的预防,重要的是通过低钠饮食和使用利尿剂优化钠与细胞外液容量的管
理
CRS3 型的预防,主要是病
因预防
CRS3 型的预防,主要是病
因预防
CRS4 型的预防,核心是
减缓 CKD 进展
CRS4 型的预防,核心是
减缓 CKD 进展
CKD5 型患者的预防应积极治疗糖尿病、淀粉样变性、肌溶解和出血性休克等原
发病
CKD5 型患者的预防应积极治疗糖尿病、淀粉样变性、肌溶解和出血性休克等原
发病
CRS 的治疗
(正(正 //负)性肌力药物治疗负)性肌力药物治疗利尿剂抵抗治疗利尿剂抵抗治疗
奈西立肽奈西立肽
加压素(抗利尿激素)拮抗剂加压素(抗利尿激素)拮抗剂
超滤超滤
腺苷受体拮抗剂腺苷受体拮抗剂
Treatment
Fig. 2. Adjusted survival curves grouped by randomization todigoxin or placebo and subsequent improved renal function(IRF) status, in patients with a serum digoxin level #0.8 ng/mL.IRF defined as $20% improvement in estimated glomerular filtrationrate (eGFR) from randomization to 1 year. Covariatesadjusted for: age, race, ejection fraction, heart rate, systolic bloodpressure, New York Heart Association functional class, diabetes,baseline use of digoxin, hydralazine, nitrates, diuretics, orangiotensin-converting enzyme inhibitors, physical examinationfindings, cardiothoracic ratio, and baseline eGFR. Overallbetween-group differences: P 5 .028. Comparisons of the YesIRF/Yes Digoxin (n 5 58) and the No IRF/No Digoxin group(n 5 409; P 5 .007), No IRF/Yes Digoxin (n 5 213; P 5.026), and Yes IRF/No Digoxin (n 5 60; P 5 .004) groupswere all statistically significant.
Nesiritide奈西立肽recombinant human B-type
natriureticpeptide (BNP), acts at the natriuretic
peptide A receptor (NPR-A)
to decrease preload, afterload, and PCWP,
increase CO, increase urine output, and improve diastolic function.
Adverse effects include headache andhypotension.
Carperitide 卡培立肽 Carperitide, or A-type natriuretic peptide (ANP),
acts as a stronger agonist than BNP at NPR-A. Its
hemodynamic effects are similar to those of nesiritide,
Although it has more robust natriuretic and diuretic effects that are more pronounced in healthy subjects than in patients with HF.
It increases and decreases MAP and PCWP, and its most common adverse effect is hypotension.
Urodilatin 肾钠素 Ularitide, the product of differential processing of the pro-ANP precursor in the kidney, acts on NPR-A in the collecting duct
thereby increasing excretion of water and sodium.
it decreased PCWP, decreased MAP, and increased CI, while down-regulating
the RAAS and improving renal sodium excretion in healthy volunteers.
The most common adverse effect is dosedependent hypotension.
CD-NP CD-NP (or ‘‘cenderitide’’) is a chimeric NP synthesized from C-type natriuretic peptide (CNP) and
Dendroaspis natriuretic peptide (DNP).
CNP originates from endothelial cells and activates NPR-B, resulting predominately in venodilation
DNP was isolated from the green mamba snake and activates NPR-A, with effects similar to those of ANP and BNP
By fusing the DNP tail to CNP, an NP is created that acts as a partial agonist of NPR-A and an agonist of NPR-B
CD-NP decreases PCWP and causes natriuresis and diuresis without a significant decrease in MAP in animal models
It significantly decreases Cr compared with furosemide in patients with stable
to cause a dose-dependent decrease in SBP
Soluble Guanylyl Cyclase Agents
Cinaciguat. Cinaciguat (or BAY 58-2667) is an NO independent sGC activator that is effective
Cinaciguat decreases diastolic blood pressure compared with placebo without significantly decreasing SBP, and in patients
with ADHF
it decreases PCWP and MAP and increases CO without significantly changing Cr.
Dose-dependent hypotension is the most common adverse effect.
RAAS-Modifying Agents
Aliskiren阿利吉仑 . Aliskiren is an oral direct renin inhibitor
that blocks formation of angiotensin I and II without affecting kinin metabolism.
decrease SVR and PCWP in patients with decompensated HF,
Decreased N-terminal prohormone of BNP (NT-proBNP),plasma renin activity, and urinary aldosterone.
Hyperkalemia,hypotension, and decreased renal function have been reported as adverse effects.
Relaxin松弛素 Relaxin, the hormone responsible for many of the maternal hemodynamic changes in
pregnancy, acts as a systemic, renal, and coronary vasodilator in animalmodels
decreasing afterload, increasing CO, and decreasing the risk of infarction during periods
of myocardial ischemia.
In humans with HF, relaxin levels were increased and correlated with disease severity
it increased CI and decreased PCWP, NT-proBNP, and Cr. No adverse effects have been reported.
Hydralazine肼苯哒嗪Hydralazine is a direct vasodilator withan unknown mechanism of action that
decreases afterload and improves stroke volume, increases renal blood flow
and has a moderate direct inotropic effect.
Adverse effects
include hypotension, nausea, headache, and tachycardia.