【作者】 黄鹏；

【导师】 许顶立；

【作者基本信息】 南方医科大学 ， 心血管内科， 2010， 硕士

【摘要】 研究背景慢性心力衰竭(CHF)是一种严重的临床综合征,它不仅表现为心泵功能的衰退,往往还同时伴有诸如肾脏、肺脏、肝脏等其他器官的功能异常。CHF早期心脏出现神经激素介导的心肌重构,心脏泵功能尚能代偿,随着病情进展,泵功能失代偿,出现症状性心力衰竭。心输出量降低导致肾血流量下降,入球小动脉收缩,肾小球滤过率下降,肾功能减退。心脏与肾脏之间存在着互相影响的病理生理变化,以神经激素以及肾素血管紧张素醛固酮系统的激活为中心环节,形成恶性循环。因此,及早发现和处理与心衰相伴的其他器官的异常,对于进一步改善心衰的预后能够起积极作用。近年来,越来越多的研究指出肾功能不全可作为心血管病的独立危险因素,住院病人的肾功能损害可以提示其心衰加重。而肾小球滤过率是精确评估肾功能的首选指标,对临床有重要的指导意义。测定GFR的方法很多。一般认为菊粉清除率是测定肾小球滤过率的金标准,但由于需要持续滴注菊粉和多次抽血,又需要导尿管,临床上不便推广,只用于科研。放射性核素肾小球滤过率测定也可以准确地反映肾小球滤过率,但价格较贵,不适宜临床普查和反复测定,也不宜用于妊娠和哺乳期的妇女。临床上比较方便应用的肾小球率过滤估算公式有：MDRD方程、简化MDRD方程、Cockcroft-Gault方程及基于胱抑素C (Cystatin C, Cys c)的估算方程。目前国外已有不少关于肾小球滤过率与心力衰竭的临床研究,但国内关于肾小球滤过率与不同心功能关系方面的报道尚少,本文就我院647例心力衰竭患者的eGFR水平和心功能分级进行分析,初步探讨HF患者eGFR水平和不同心功能分级之间的关系。目的以2007年1月至2009年6月间于广州南方医院入院心内科住院的心力衰竭(HF)患者(647例)为研究对象,并选取同期住院无心力衰竭且年龄性别相当的其他患者(54例)为对照组,应用MDRD方程、简化MDRD方程、Cockcroft-Gault方程及基于胱抑素C(Cystatin C,Cys c)的估算方程分别计算每个患者的肾小球滤过率(GFR),分析GFR水平与不同心功能分级之间的关系,了解GFR水平与LVEF.NT-proBNP、CRP、UA等因素的关系,进一步探讨GFR在心力衰竭患者中的临床意义。方法收集CHF患者与对照组的病例资料：HF的诊断结合病史、临床表现、体检和心脏彩超,分为初发的急性左心衰和慢性心力衰竭,后者按照NYHA心功能分级分为Ⅰ、Ⅱ、Ⅲ、Ⅳ级,5组病例数分别为18、31、200、253、145例。选取无心力衰竭且年龄性别相当的患者54例作为对照组。排除标准：研究期间第2次及以上再次入院的患者,因各种原因未能在住院24h内清晨空腹采血的患者及原发性肾脏疾病的患者。所有对象于入院当日或第二天清晨采血,送南方医院检验科检查血常规、肝肾功能、NT-proBNP、CRP等项目,入院2-3日内完成超声心动图检查,测定左心室射血分数(LVEF)等指标。选用目前临床常用的4种预测方程计算eGFR:(1)MDRD公式：GFR=170×血肌酐-0.999×年龄-0.176×尿素氮-0.170×白蛋白0318×(0.762女性)；(2)简化MDRD公式：GFR=186.3×(Scr)-1.154×(年龄)-0.203×(0.742女性)。(3)Cockcroft-Gault方程：GFR=Ccr×0.84×1.73／BSA；Ccr=[(140-年龄)×体重(kg)×(0.85女性)]／(72×Scr)；BSA=0.007184×体重0.425×身高0.725。(4)基于胱抑素C (Cystatin C)的GFR估算公式：GFR=66.8×Cys-c-1．30。上述公式中所用的单位：GFR (ml/min·1.73m2)、年龄(岁)、体重(kg)、身高(cm)、血清Cr(mg/dl)、BUN(mg/dl)、Alb(g/dl)、Cys-c (mg/l)。应用SPSS 13.0软件包进行统计学处理。所有数据以x±s表示,2组间均数的显著性检验采用两独立样本t检验,多组间比较采用单因素方差分析(One-way ANOVA),经Levene方差齐性检验,如满足方差齐性,各组间两两比较采用LSD法,如方差不齐,各组间比较则采用Dunnett法,两变量相关性分析采用Pearson相关分析。P<0.05认为差异有统计学意义。结果1、简化MDRD公式计算出的GFR水平与不同心功能的关系简化MDRD公式计算出的GFR水平在对照组、心功能Ⅱ级组、心功能Ⅰ级组、心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组中逐渐降低。GFR水平在心功能Ⅰ级组与急性左心衰组、对照组之间有显著性差异；心功能Ⅱ级组与心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组、对照组之间有显著性差异；心功能Ⅲ级组与对照组之间有显著性差异；心功能Ⅳ级组与对照组之间有显著性差异(P<0.05)；急性左心衰组与对照组之间有显著性差异；其他各组间无统计学差异。2、MDRD公式计算出的GFR水平与不同心功能的关系MDRD公式计算出的GFR水平在对照组、心功能Ⅱ级组、心功能Ⅰ级组、心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组中逐渐降低。GFR水平在心功能Ⅰ级组与心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组之间有显著性差异；心功能Ⅱ级组与心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组、对照组之间有显著性差异；心功能Ⅲ级组与心功能Ⅳ级组、对照组之间有显著性差异；心功能Ⅳ级组与对照组之间有显著性差异(P<0.05)；急性左心衰组与对照组之间有显著性差异；其他各组间无统计学差异。3、Cockcroft-Gault方程计算出的GFR水平与不同心功能的关系Cockcroft-Gault方程计算出的GFR水平在对照组、急性左心衰组、心功能Ⅱ级组、心功能Ⅰ级组、心功能Ⅳ级组、心功能Ⅲ级组中逐渐降低。GFR水平在心功能Ⅱ级组与心功能Ⅲ级组、心功能Ⅳ级组之间有显著性差异；心功能Ⅲ级组与对照组之间有显著性差异；心功能Ⅳ级组与对照组之间有显著性差异；其他各组间无统计学差异。4、基于Cys c (Rule)的公式计算出的GFR水平与不同心功能的关系基于Cys c (Rule)的公式计算出的GFR水平对照组、心功能Ⅱ级组、心功能Ⅰ级组、心功能Ⅲ级组、心功能Ⅳ级组、急性左心衰组中逐渐降低。GFR水平在心功能Ⅱ级组与心功能Ⅲ级组、心功能Ⅳ级组之间有显著性差异；心功能Ⅲ级组与对照组之间有显著性差异；心功能Ⅳ级组与对照组之间有显著性差异；急性左心衰组与对照组之间有显著性差异；其他各组间无统计学差异。5、四种估算GFR水平的公式之间相关性分析直线相关分析显示：eGFR(sMDRD)与eGFR (MDRD)、eGFR (Cockcroft-Gault)、eGFR (Cys c)呈显著的正相关,r值分别为0.965、0.886、0.727,均P<0.001；eGFR (MDRD)与eGFR (Cockcroft-Gault)、eGFR (Cys c)呈显著的正相关,r值分别为0.895、0.731,均P<0.001; eGFR (Cockcroft-Gault)与eGFR (Cys c)呈显著的正相关,r=0.708,P<0.001。6、NT-proBNP与GFR的相关分析直线相关分析显示：NT-proBNP与eGFR (sMDRD)、eGFR (MDRD)、eGFR (Cockcroft-Gault)呈显著的负相关,r值分别为-0.307、-0.381、-0.308,均尺0.001。提示NT-proBNP水平越高(即心衰程度越重),eGFR水平越低,肾功能越差。NT-proBNP与eGFR (Cys c)的相关分析结果为：r=-0.207,P=0.059,无统计学意义。7、LVEF与GFR的相关分析直线相关分析显示：LVEF与eGFR (sMDRD)、eGFR (MDRD)、eGFR (Cockcroft-Gault)呈正相关,r值分别为0.109、0.140、0.180,均P<0.05。提示心脏左室射血分数越好,eGFR水平也越高,肾功能越好。LVEF与eGFR (Cysc)的相关分析结果为：r=0.034,P=0.732,无统计学意义。8、UA与GFR的相关分析直线相关分析显示：UA与eGFR(sMDRD)、eGFR(MDRD)、eGFR(Cockcroft-Gault)、eGFR (Cys c)呈显著负相关,r值分别为-0.315、-0.400、-0.383、-0.295,均P<0.001。UA作为肾功能的一项指标,水平越高,提示肾功能越差,而eGFR水平也越低。9、CRP与GFR的相关分析直线相关分析显示：CRP与eGFR(sMDRD)、eGFR(MDRD)、eGFR(Cockcroft-Gault)呈显著负相关,r值分别为-0.167、-0.206、-0.240,均P<0.05。CRP与eGFR (Cys c)的相关分析结果为：r=-0.076,P=0.410,无统计学意义。10、射血分数正常的CHF患者与射血分数减低的CHF患者eGFR水平的比较射血分数减低的CHF患者(LVEF<40%)和射血分数正常的CHF患者(LVEF≥40%)之间eGFR水平比较无统计学差异(74.47±30.49 ml/min·1.73m2 vs.70.77±28.11 ml/min·1.73m2,/P=0.251)。结论1、CHF患者的eGFR水平低于对照组,并随心功能分级的增加呈减少趋势。2、四种GFR估算公式所计算出的eGFR水平均呈显著正相关,其中以简化MDRD公式与MDRD公式所计算出的eGFR水平的相关性最高,而以Cys-c的GFR估算公式与Cockcroft-Gault公式所计算出的eGFR水平的相关性最低。3、CHF患者的eGFR水平与NT-proBNP、UA、CRP水平呈负相关,与LVEF水平呈正相关。4、射血分数减低的CHF患者(LVEF<40%)和射血分数正常的CHF患者(LVEF≥40%)之间eGFR水平比较无统计学差异。更多还原

【Abstract】 Reserch backgroundChronic heart failure (CHF) is a severe clinical syndrome, it is not only for the heart pump function decline, also accompanied by kidneys, lungs, liver and other organs dysfunction. In the initial stage of CHF, there is neurohormonal-mediated myocardial remodeling, and the heart pump function is still capable of compensation, along with the progress of the disease, the pump function decompensated, and heart failure symptoms come. Reduced cardiac output leading to decreased renal blood flow, decreased glomerular filtration rate and renal dysfunction. Between the heart and kidney, there are pathological physiological changes which affect each other, neurohormonal and renin-angiotensin-aldosterone system activate as the central link, form a vicious cycle. Therefore, early detection and treatment of other organs’ anomaly accompanied with heart failure, can play an active role for improving the prognosis of heart failure.Recently, lots of studies have pointed out that renal insufficiency can be used as an independent risk factor for cardiovascular disease, impaired renal function of patients may be prompted to aggravation of heart failure. glomerular filtration rate is the best indicator of renal function for accurate assessment of renal function, which have important clinical significance. There are many ways for measuring GFR. The determination of inulin clearance rate is the best way to estimate glomerular filtration rate, but it’s not suitable for clinical use, only suitable for scientific research. Radionuclide glomerular filtration rate can be determined accurately, which reflect the glomerular filtration rate accurately, but the price is expensive, not suitable for clinical screening and repeated measurement, and also not suitable for pregnant and lactating women. The convenient formula for estimating glomerular filtration rate are MDRD formula, simplified MDRD formula, Cockcroft-Gault formula and formula based on Cystatin C (Cys c). At present, there are quite a number of clinical researches on the glomerular filtration rate in patients with heart failure in foreign countries, but there is only few report of the relationship between glomerular filtration rate and different cardiac function, In this research, we analyzed and discussed the relationship between glomerular filtration rate and different cardiac function(647 cases of heart failure patients).Object647 patients with heart failure were divided into 2 groups, acute heart failure group(18 patients) and chronic heart failure group(629 patients),629 CHF patients were divided into 4 groups according to the New York Heart Association (NYHA) criteria, The number of NYHAⅠ-Ⅳwas 236,138,132,59 respectively,54 patients who did not have heart failure were involved as control group. we calculated the glomerular filtration rate by MDRD formula, simplified MDRD formula, Cockcroft-Gault formula and formula based on Cystatin C (Cys c), analyzed and discussed the relationship between glomerular filtration rate and different cardiac function and the relationship between glomerular filtration rate and left ventricular ejection fraction(LVEF), N-terminal pro-brain natriuretic peptide(NT-proBNP), C-reactive protein(CRP), uric acid(UA).MethodsCollect the information of CHF patients and control group patients.647 patients with heart failure were divided into 2 groups, acute heart failure group(18 patients) and chronic heart failure group(629 patients),629 CHF patients were divided into 4 groups according to the New York Heart Association (NYHA) criteria, The number of NYHAⅠ-Ⅳwas 236,138,132,59 respectively,54 patients who did not have heart failure were involved as control group. we calculated the glomerular filtration rate by MDRD formula, simplified MDRD formula, Cockcroft-Gault formula and formula based on Cystatin C (Cys c), and examine the level of left ventricular ejection fraction(LVEF), N-terminal pro-brain natriuretic peptide(NT-proBNP), C-reactive protein(CRP), uric acid(UA), serum creatinine(Scr), Blood Urea Nitrogen(Bun), albumin(Alb), Cystatin C (Cys c).The formula we commonly used in clinic includes:(1) MDRD formula: GFR=170×Scr-0.999×age-0.0176×bun-0.170×alb0.318×(0.762 female); (2) simplified MDRD formula:GFR=186.3×(Scr)-1.154×(age)-0.203×(0.742 female)。(3) Cockcroft-Gault formula:GFR=Ccr×0.84×1.73/BSA; Ccr=[(140-age)×weight(kg)×(0.85 female)]/(72×Scr); BSA=0.007184 X weight0.425×height0.725. (4) formula based on Cystatin C (Cys c):GFR=66.8 X Cys c-1.30。The unit in formulas above:GFR (ml/min·1.73m2)、age(year)、weight(kg) height (cm)、Scr(mg/dl)、bun(mg/dl)、alb(g/dl)、Cys c (mg/l)。A statistical software package(SPSS 13.0) were employed for data analyze. All data were showed ad mean±standard deviation(x±s). Means between two groups were compared by two-independent sample t-test. Means among groups were analyzed by one-way ANOVA. After the Levene test of homogeneity of variance, if the homogeneity of variance of data was well, LSD test was applied for inner-group, if the homogeneity of variance of data was not well, Dunett test was applied for inner-group. The correlation between two normal distribution measurement data was showed by Pearson correlation. The difference was statistically significant if P <0.05.Resultsl.The relationship between heart function and GFR estimated by simplified MDRD formulaThe GFR estimated by simplified MDRD formula decreased in control group, NYHAⅡgroup, NYHAⅠgroup, NYHAⅢgroup, NYHAⅣgroup and acute heart failure group gradually. There is significant difference between NYHAⅠ group and acute heart failure group, control group. There is significant difference between NYHAⅡgroup and NYHAⅢgroup, NYHAⅣgroup, control group. There is significant difference between NYHAⅢgroup and control group. There is significant difference between NYHAⅣgroup and control group. There is significant difference between acute heart failure group and control group (P <0.05). There is no significant difference among other groups.2. The relationship between heart function and GFR estimated by MDRD formulaThe GFR estimated by MDRD formula decreased in control group, NYHAⅡgroup, NYHAⅠgroup, NYHAⅢgroup, NYHAⅣgroup and acute heart failure group gradually. There is significant difference between NYHAⅠgroup and NYHAⅢgroup, NYHAⅣgroup,acute heart failure group. There is significant difference between NYHAⅡgroup and NYHAⅢgroup, NYHA IV group, acute heart failure group, control group. There is significant difference between NYHAⅢgroup and NYHA IV group, control group. There is significant difference between NYHA IV group and control group. There is significant difference between acute heart failure group and control group (P<0.05). There is no significant difference among other groups.3. The relationship between heart function and GFR estimated by Cockcroft-Gault formulaThe GFR estimated by Cockcroft-Gault formula decreased in control group, acute heart failure group, NYHAⅡgroup, NYHAⅠgroup, NYHAⅣgroup and NYHAⅢgroup gradually. There is significant difference between NYHAⅡgroup and NYHAⅢgroup, NYHA IV group. There is significant difference between NYHAⅢgroup and control group. There is significant difference between NYHAⅣgroup and control group. There is no significant difference among other groups.4. The relationship between heart function and GFR estimated by formula based on Cystatin C The GFR estimated by formula based on Cystatin C decreased in control group, NYHAⅡgroup, NYHAⅠgroup, NYHAⅢgroup, NYHAⅣgroup and acute heart failure group gradually. There is significant difference between NYHAⅡgroup and NYHAⅢgroup, NYHA IV group. There is significant difference between NYHAⅢgroup and control group. There is significant difference between NYHAⅣgroup and control group. There is significant difference between acute heart failure group and control group. There is no significant difference among other groups.5.The correlation among formulasPearson correlation test showed that, eGFR(sMDRD) with eGFR(MDRD), eGFR(Cockcroft-Gault) and eGFR(Cys c) had positive correlations(r=0.965,0.886, 0.727 respectively, P<0.001). eGFR(MDRD) with eGFR(Cockcroft-Gault) and eGFR(Cys c) had positive correlations(r=0.895,0.731 respectively, P<0.001). eGFR(Cockcroft-Gault) and eGFR(Cys c) had positive correlations. (r=0.708, P <0.001).6. The correlation between NT-proBNP and GFRPearson correlation test showed that, NT-proBNP with eGFR(sMDRD), eGFR(MDRD), and eGFR(Cockcroft-Gault) had negative correlations(r=-0.307,-0.381,-0.308 respectively, P<0.001).7. The correlation between LVEF and GFRPearson correlation test showed that, LVEF with eGFR(sMDRD), eGFR(MDRD) and eGFR(Cockcroft-Gault) had positive correlations(r=0.109,0.140,0.180 respectively, P<0.05).8. The correlation between UA and GFRPearson correlation test showed that, UA with eGFR(sMDRD), eGFR(MDRD), eGFR(Cockcroft-Gault) and eGFR(Cys c) had negative correlations(r=-0.315,-0.400,-0.383,-0.295 respectively, P<0.001).9. The correlation between CRP and GFRPearson correlation test showed that, CRP with eGFR(sMDRD), eGFR(MDRD) and eGFR(Cockcroft-Gault) had negative correlations(r=-0.167,-0.206,-0.240 respectively,P<0.05).10.The GFR between normal LVEF CHF patients and low LVEF CHF patientsThere is no significant difference between two group.(74.47±30.49 ml/min·1.73m2 vs.70.77±8.11 ml/min·1.73m2,P=0.251)Cnclusion1.The eGFR is lower in CHF patients than that in control group, and it shows a decreasing trend with the increase of heart function classification.2.The GFR estimated by four formulas shows positive correlation with each other.3.The eGFR in CHF patients has negative correlation with NT-proBNP, UA and CRP, has positive correlation with LVEF.4. The eGFR level had no significant difference between normal LVEF CHF patients and low LVEF CHF patients.更多还原