B-Type Natriuretic Peptide and Renal Disease

B-type natriuretic peptide (BNP) is a cardiac neurohormone which has a principal effect on the kidney to signal both natriuresis and diuresis. Both BNP and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, the relationships between BNP, renal function, and CHF as an emergency diagnosis, are not completely understood. The correlation between BNP and estimated glomerular filtration rate (eGFR) is approximately r = –0.20. At an eGFR <60 ml/min/1.73 m², the optimum cutpoint for BNP to diagnose CHF rises to approximately 200 pg/ml. At this cutpoint the area under the receiver operating characteristic curve is 0.81, indicating that BNP is of diagnostic value in this group. Importantly, the precursor molecule N-terminal proBNP has a stronger correlation with eGFR of approximately –0.60, and is influenced by the age-related decline in renal function above the lower bounds of normal of <60 ml/min/1.73 m². Because BNP is a principal messenger from the heart to the kidneys, and because it is influenced by renal filtering function, parenchymal mass, and tubular function, BNP can be leveraged in assisting in the diagnosis and management of combined heart and renal failure.     

脑利钠肽在心血管疾病中的研究进展

随着心力衰竭(心衰)的发展,心脏分泌物脑利钠肽(BNP)也随着增加.目前已有大量的临床研究显示BNP可作为心衰诊断和预后的生物学标志,并可用来鉴别肺源性和心源性呼吸困难,在失代偿的心衰中BNP的治疗用途更是一项新的进展.目前也有研究表明在其它的心血管病理状态,包括心肌缺血、心肌纤维化、心脏肥厚、冠状动脉内皮功能障碍和冠脉粥样硬化等BNP水平也是升高的.此外,发现轻度升高的BNP水平对将来的心血管事件有着评估预后的价值.这些发现使BNP可能成为许多心血管病理状态的最后通路.     

B-Type Natriuretic Peptide: Physiologic Role and Assay Characteristics

The discovery of cardiac natriuretic peptides two decades ago has lead to considerable research to investigate their biochemical and physiological properties. Clearly the heart is not just a pump but is also an endocrine organ that together with the kidneys control volume overload. The natriuretic peptides are a group of structurally similar but genetically distinct peptides that exhibit diverse actions in cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are of myocardial cell origin. BNP is released mainly from the left ventricle in response to volume overload and has become the first biochemical marker for the identification of individuals with congestive heart failure (CHF). The development of assays, including rapid point-of-care tests, has made BNP measurement a clinical reality.     

B-Type Natriuretic Peptide and the Right Heart

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.     

B型脑钠肽对预测心力衰竭时恶性心律失常的价值

目的探讨左心衰竭患者血浆B型脑钠肽（BNP）浓度与恶性室性心律失常的关系。方法采用荧光免疫法测定52例左心衰竭患者入院时和治疗2周后的BNP浓度,连续心电监测住院期间（Lonwn分级Ⅲ级以上）的恶性室性心律失常、心脏性猝死、心力衰竭加重和急性心肌梗死等事件。结果随着BNP浓度的增高,恶性室性心律失常和急性心脏事件的发生率也明显增高（P〈0．05）;随着心功能的好转,BNP浓度下降（P〈0．05）,恶性室性心律失常和急性心脏事件的发生率也下降（P〈0．05）。结论血浆BNP浓度对心力衰竭时恶性心律失常事件的发生具有重要预测价值。     

B型利钠肽对心力衰竭患者心源性事件的预测价值

目的:评价B型利钠肽(BNP)对左心衰竭患者的预后预测价值.方法:使用荧光免疫的方法测定心力衰竭患者的BNP,并进行随访.主要临床终点为:心源性死亡和再入院.根据随访结果将患者分为无再发事件组(162例),心源性再入院组(47例),心源性死亡组(54例).用Kaplan-Meier法计算生存率和无心脏事件生存率,多因素分析采用COX回归分析法.结果:300例患者平均随访(9.5±5.6)个月,心源性再入院组[482.0(227.0,793.0)pg/ml]及心源性死亡组[565.0(327.3,1192.5)pg/ml]的BNP水平均显著高于无再发事件组[146.5(51.7,374.3)pg/ml)(P均＜0.001).不论单因素还是多因素分析,包括年龄、性别、纽约心功能分级(NYHA)、超声心动图所测左心房前后径、左心室舒张末内径、左心室射血分数(LVEF)及Log BNP,仅Log BNP与心源性死亡时问及心源性再入院时间独立相关.当分别引入Log BNP,性别,年龄,NYHA,LVEF和左心室舒张末内径及是否伴有心房颤动、心房扑动、室性心动过速、糖尿病共10个因素,单因素分析中:Log BNP、性别、NYHA、LVEF和室性心动过速是心源性事件发生的预测因子.但进一步COX多元回归分析中,只有Log BNP(回归系数:0.9898;P=0.002)和室性心动过速(回归系数:0.893;P=0.005)是独立相关影响因素.两者中,又以Log BNP的相关性最强.根据受试者工作特征曲线(ROC),BNP 288 pg/ml为划分有无心源性事件发生的最佳阈值点.BNP≤288 pg/ml患者的无心源性事件生存时间约是＞288 pg/ml患者的两倍(18.06个月vs 9.94个月,P=0.000).结论:BNP对心力衰竭患者的预后预测价值好.Log BNP和室性心动过速是心源性死亡、再入院事件独立相关影响因素.     

Olmesartan Medoxomil Treatment Is Associated with Decreased Plasma B-Type Natriuretic Peptide Levels in Patients on Hemodialysis

Background. High levels of plasma B-type natriuretic peptide (BNP) are associated with cardiac heart failure and death among patients on hemodialysis (HD). A recent study has demonstrated that the angiotensin II type 1 receptor blocker lowers BNP concentrations. Here, we examined whether the ability of olmesartan medoxomil (OM; a novel angiotensin II type 1 receptor blocker) to decrease plasma BNP levels is concentration dependent in hypertensive patients on HD. Methods. This preliminary, observational, open-labeled prospective study included 24 patients on HD who were assigned to one group treated with OM (n = 14) or to an age-matched control group that was conventionally treated (n = 10). Blood pressure (BP) was monitored in the morning and evening of a non-HD day and before each HD session, and plasma BNP, plasma aldosterone (PAC), plasma active renin (PARC), and OM concentrations were measured at baseline, 4, and 8 weeks after treatment. Results. Plasma BNP levels were significantly decreased in the OM group, but remained unchanged in the control group after 4 and 8 weeks of treatment. Compared with the control group, OM was associated with increased PARC and decreased PAC levels. The OM concentrations at 4 and 8 weeks significantly correlated with depressed plasma BNP levels in accordance with multiple regression analysis adjusted for confounders including BP. Conclusion. These results suggest that OM can help to decrease plasma BNP levels via a concentration-dependent effect in patients on HD.     

慢性心力衰竭患者B型利钠肽与尿酸的变化及意义

目的:探讨B型利钠肽(BNP)、尿酸浓度在慢性心力衰竭(CHF)时的变化及心功能与超声心动图指标的相关性.方法:2007-03至2008-05我院住院患者中,102例因心功能失代偿而入院的CHF患者为CHF组;无CHF 26例作为对照组.患者人院后均行BNP、尿酸和超声心动图检查,BNP浓度以放射免疫法测定,尿酸浓度以自动分析仪测定.CHF组根据美国纽约心脏协会(NYHA)心功能分级标准分为Ⅱ、Ⅲ、Ⅳ级.结果:与对照组比较,CHF组BNP浓度显著增高,差异有统计学意义(P<0.01);NYHAⅣ级及NYHAⅢ级患者的BNP浓度均较NYHAⅡ级高,差异有统计学意义(P均<0.01);NYHAⅣ级及NYHAⅢ级患者的尿酸浓度较对照组和NYHAⅡ级显著增高,差异均有统计学意义(P均<0.01).CHF时BNP浓度与NYHA分级存在正相关关系(γ=0.785,P<0.01);与左心室射血分数存在负相关关系(r=-0.316,P<0.01).CHF时尿酸浓度与NYHA分级存在正相关关系(r=0.402,P<0.01);与左心室射血分数无直线相关关系.结论:CHF时BNP及尿酸浓度随着心力衰竭程度的加重而相应升高.BNP与左心功能状态有良好的相关性,而尿酸的这种相关性较差.BNP评价CHF时优于尿酸.尿酸水平是反映CHF病情严重程度的一个有意义的指标,尤其在CHF程度重(NYHAⅣ级及NYHAⅢ级)的患者更为明显.     

双腔起搏对血浆脑钠肽值的影响

目的 探讨双腔起搏器心室起搏比例与血浆脑钠肽值的关系。方法52例双腔起搏器植入患者分别在术后和房室延迟调整后第3个月末程控测取心室起搏比例及血浆脑钠肽值,并按心室起搏比例分成≥40％组（35例）和〈40％组（17例）。结果术后心室起搏比例≥40％组和〈40％组的血浆脑钠肽对数值分别为2．06±0.26和1．77±0．28,差异有非常显著性意义（P〈0．01）。心室起搏比例≥40％组经过房室延迟调整后心室起搏比例从（65．0±12．3）％下降为（44．1±7．3）％,血浆脑钠肽对数值从2．06±0．26下降为1．79±0．31,差异有非常显著性意义（P〈0．01）。结论减少双腔起搏器的非必需心室起搏,可减少对心功能及血流动力学的不利影响。     

B-Type Natriuretic Peptide: Spectrum of Application. Nesiritide (Recombinant BNP) for Heart Failure

The therapeutic goals for patients hospitalized with acutely decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and to initiate heart failure therapies which will decrease disease progression and improve long-term survival. Nesiritide (recombinant B-type natriuretic peptide) is the first in a new class of therapeutic agents for the treatment of heart failure and has been demonstrated to offer a unique combination of safety and efficacy. The use of nesiritide on top of standard care including diuretic therapy, has been proven to lead to meaningful clinical benefits in a broad range of acutely decompensated heart failure patients. Nesiritide is an attractive therapeutic option because of its more rapid and sustained hemodynamic profile, more favorable effects on neurohormonal suppression, with less adverse effects than alternative intravenous heart failure treatments such as nitroglycerine, nitroprusside, dobutamine, or milrinone. The use of nesiritide is the most effective initial treatment approach among currently available strategies to reverse acutely decompensated heart failure and to facilitate optimization of the heart failure medical regimen.     

B型利钠肽检测在鉴别心原性和肺原性呼吸困难中的价值

目的:探讨血浆B型利钠肽(BNP)水平在鉴别慢性心力衰竭(心衰)和肺原性疾病导致呼吸困难中的临床价值。方法:对230例因呼吸困难收入急诊室的患者,床旁测试BNP值,最后由两名事前不知道BNP测试结果,各自独立的心内科医师判断这些患者是否患有慢性心衰。结果:慢性心衰患者(n=136)的血浆BNP水平为(996.3±78.2)pg/ml,明显高于最后诊断为肺部疾病的患者(n= 76),其BNP值为(70.8±21.4)pg/ml(P<0.01),有左心室功能不全但呼吸困难最终确定并非心脏原因引起的患者(n= 18),BNP值为(162.5±41.7)pg/ml。用100 pg/ml作为BNP界值时,其诊断的准确性为91%,多变量分析表明,在预测慢性心衰的各变量中BNP测定比其他的变量更具独立和重要的诊断价值。结论:血浆BNP水平有助于区分呼吸困难是否为慢性心衰或肺部疾病。     

B型利钠肽对慢性心力衰竭的诊断价值及与左心功能的关系

目的:探讨血浆B型利钠肽(BNP)水平在慢性心力衰竭(CHF)中的诊断价值,以及血浆BNP与CHF严重程度和左心室功能的关系.方法:对96例根据病史、体征、心脏X线胸片、实验室检查及对治疗反应等临床诊断为CHF的患者,就诊后24 h内取静脉血测定血浆BNP,并行超声心动图检查,分析血浆BNP与NYHA心功能分级及左心室射血分数之间的关系.结果:按照心功能分级,Ⅰ～Ⅳ级患者血浆BNP逐步增加(P＜0.001);左心室舒张末期内径≤55 mm的血浆BNP显著低于内径＞55mm者(P＜0.01);且左心室射血分数≤0.50的血浆BNP显著大于射血分数＞0.50者(P＜0.001).结论:血浆BNP水平提示能客观的反映心功能的情况,可作为一种简便快速的手段用于CHF的诊断及危险分层.     

Risk Factors for Heart Failure in Patients With Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated With Bardoxolone Methyl

BackgroundA phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2–related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.Methods and ResultsWe randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min⁻¹ 1.73 m⁻²) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl– and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.ConclusionsBardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.     

Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKD

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Association of BP with Death,Cardiovascular Events,and Progression to Chronic Dialysis in Patients with Advanced Kidney Disease

Background and objective

The optimal BP target to reduce adverse clinical outcomes in patients with CKD is unclear. This study examined the relationship between BP and death, cardiovascular events (CVEs), and kidney disease progression in patients with advanced kidney disease.

Design, setting, participants, & measurements

The relationship of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) with death, CVE, and progression to long-term dialysis was examined in 1099 patients with advanced CKD (eGFR≤30 ml/min per 1.7 3m²; not receiving dialysis) who participated in the Homocysteine in Kidney and ESRD study. That study enrolled participants from 2001 to 2003. Cox proportional hazard models were used to examine the association between BP and adverse outcomes.

Results

The mean±SD baseline eGFR was 18±7 ml/min per 1.73 m². During a median follow-up of 2.9 years, 453 patients died, 215 had a CVE, and 615 initiated long-term dialysis. After adjustment for demographic characteristics and confounders, SBP, DBP, and PP were not associated with a higher risk of death. SBP and DBP were also not associated with CVE. The highest quartile of PP was associated with a substantial higher risk of CVE compared with the lowest quartile (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.10 to 2.52). The highest quartiles of SBP (HR, 1.28; 95% CI, 1.01 to 1.61) and DBP (HR, 1.36; 95% CI, 1.07 to 1.73), but not PP, were associated with a higher risk of progression to long-term dialysis compared with the lowest quartile.

Conclusions

In patients with advanced kidney disease not undergoing dialysis, higher PP was strongly associated with CVE whereas higher SBP and DBP were associated with progression to long-term dialysis. These results suggest that SBP and DBP should not be the only factors considered in determining antihypertensive therapy; elevated PP should also be considered.