肾功能与N末端B型钠尿肽原的关系及其在慢性心力衰竭诊断中的应用

目的通过观察人血清预测肾小球滤过率(eGFR)与N末端B型钠尿肽原(NT-proBNP)之间的关系,比较慢性心力衰竭(简称心衰)患者不同eGFR水平NT-proBNP的诊断界值(cut-off值),研究肾功能对NT-proBNP应用于心衰诊断的影响。方法选择我院2003年10月至2004年4月明确诊断为心衰的住院患者106例(心衰组)以及同期正常对照191名(对照组)。采用电化学发光法测定受试者血清NT-proBNP浓度,应用Levey改良的饮食校正公式计算eGFR。结果肾功能异常者[eGFR<60ml·(min·1·73m2)-1]的NT-proBNP中位数水平显著高于肾功能正常者[eGFR≥60ml·(min·1·73m2)-1],无论是在心衰组(829·1ng/Lvs·227·2ng/L,P<0·01)还是对照组(85·5ng/Lvs·50·4ng/L,P<0·01)。将NT-proBNP与eGFR进行对数转换后,二者呈负相关(心衰组r=-0·271,P<0·01;对照组r=-0·353,P<0·01)。NT-proBNP诊断肾功能正常心衰患者的cut-off值为162·3ng/L,敏感度为68·3%,特异度为98·1%,阳性预测值(PPV)为94·9%,阴性预测值为(NPV)85·3%,AUC为0·901;而诊断肾功能异常心衰患者的cut-off值明显升高,为238·8ng/L,敏感度为70·8%,特异度为100%,PPV为100%,NPV为84·1%,AUC为0·863。结论肾功能与NT-proBNP呈微弱相关,肾功能异常时NT-proBNP诊断心衰的cut-off值升高,可以作为合并肾功能不全心衰的诊断指标。     

肾功能不全对应用NT-proBNP评估心功能的影响

目的研究肾功能不全的严重程度对血清NT-proBNP评估心功能的影响。方法选择临床诊断冠心病患者174例,用电化学发光法测定血清NT-proBNP水平,酶法检测血清肌酐水平,超声心动图检查测定心脏射血分数（EF值）,并记录性别、年龄、体重、糖尿病分型、高血压分级,用MDRD公式计算肾小球滤过率eGFR,生化方法检测血清血糖、血脂水平,统计分析不同eGFR对血清NT-proBNP评估心功能能力的影响。结果。肾功能轻中度异常的患者（eGFR〉60）,EF=-0．78Log（NT-proBNP）＋0．852,R2linear=0．287,F=27．308,P〈0．01,血清NT-proBNP浓度的对数值与EF值呈显著的负相关;而肾功能中重度异常的患者（eGFR〈60）,R2 linear=0．027,F=0．210,P=0．655,血清NT-pmBNP浓度的对数值与EF值不成线性相关,且高密度脂蛋白胆固醇和载脂蛋白A较前者明显降低。冠心病患者中性别差异对肾功能不全的影响有显著性差异。结论肾功能中重度异常的患者,血清NT-proBNP浓度不能正确反应心脏功能,需要进步一校正,尤其对于女性患者应提高警惕。     

急性心肌梗死后康复运动患者的心脏功能评价

目的检测急性心肌梗死(AMI)患者进行早期指导性康复运动和无康复运动者分别在发病第3天及3个月时血清N末端B型钠尿肽前体(NT-proBNP)的水平、左室射血分数(LVEF)和左室舒张末期直径(LVDd)的变化,探讨AMI无严重并发症患者早期康复运动的血清NT-proBNP水平、心脏功能情况。方法选择54例AMI无严重并发症患者,运动组29人(运动+药物治疗),非运动组25人(仅药物治疗)。在AMI第3天做超声心动图检查及检测患者血清NT-proBNP水平,于AMI后3个月时重复上述检查。结果(1)运动组的患者心梗第3天及3个月时NT-proBNP水平从1076.00(666.50-1723.50)ng/L显著下降至211.00(141.75-374.00)ng/L(P<0.05),非运动组的患者血清NT-proB-NP水平从573.00(231.00-1059.50)ng/L降至462.10(218.30-1042.00)ng/L,无显著变化。3个月时两组间有显著性差异(P<0.01)。(2)运动组患者心梗的第3天及3个月时LVDd(50.63±4.89)mm增加到(50.78±4.10)mm没有显著变化,但非运动组的患者从(50.31±4.27)mm增加到(51.85±4.37)mm,LVDd呈显著增加。3个月时两组间LVDd比较有显著性差异(P<0.01)。(3)运动组患者心梗第3天及3个月时的LVEF从(55±9)%升高到(60±8)%,LVEF呈显著升高(P<0.05),非运动组的患者(53±9)%减少到(52±8)%,无显著性变化。3个月时两组间LVEF值有显著性差异(P<0.05)。结论AMI无严重并发症患者早期进行指导性康复运动是安全可行的,可以降低患者血清NT-proBNP水平,增加左室射血分数,可能降低左室舒张末期直径。     

Effect of intravenous vancomycin on renal function

In the past, vancomycin has been reported to cause renal failure during intravenous administration; however, more recently, such renal toxicity is alleged not to occur because of increased purity of the vancomycin preparations. In this study, 23 patients were prospectively examined during intravenous vancomycin administration for changes in renal function. Vancomycin was administered for an average of 15 days. The blood urea nitrogen (BUN) changes averaged +1.7 mg/dl and the creatinine changes averaged +0.06 mg/dl. Since the accuracy of the serum creatinine determination was +/- 0.3 mg/dl, clinically significant deterioration of renal function occurred in 4 patients or 17%. Even among these 4 patients with documented worsening of renal function, we suspect that deterioration was related to the infection being treated. With close monitoring of dosing, the propensity of vancomycin to cause nephrotoxicity may be less than once thought.     

Effect of high-dose etodolac on renal function

Previous studies from our laboratory have demonstrated transient effects on renal function by etodolac, 200 mg b.i.d. The current study assessed the effects of a larger dose of etodolac (500 mg b.i.d.) to explore the time course of its renal effects and to determine whether the transient effect would become more prolonged with a larger dose. We studied 10 normal subjects and nine patients with renal insufficiency, examining the effects of the first 500 mg dose of etodolac as well as 4 days of b.i.d. administration. In both groups, etodolac transiently decreased fractional excretions of sodium and chloride and urinary prostaglandin E2. In patients, etodolac also transiently decreased inulin and para-aminohippuric acid clearances and urinary 6-keto-prostaglandin F1 alpha. Chronic administration caused no changes in renal function in either group. In summary, in this relatively small group of patients, high-dose etodolac caused only transient, fully reversible effects on renal function, the cumulative effect of which was negligible.     

Effect of anesthesia and surgery on renal function

Interpretation of the effects of anesthesia and surgery on renal function should be based on careful appraisal of the methodology used. Currently, the most accurate measurement of in vivo RBF is provided by flow probes, although thermodilution techniques show promise. In addition, the many secondary factors that affect renal responses, such as intravascular volume status and positive pressure ventilation, should be taken into consideration in evaluating any study. Normal renal function appears to be regulated by a balance between opposing neurohormonal systems which control vasomotor tone, diuresis, and natriuresis. Surgical stress tips the balance in favor of renal vasoconstriction and salt and water retention, which may last for days after operation. Recent elucidation of the role of atrial natriuretic peptide enhances the concept that these changes can be prevented or modified by maintenance of normal or increased atrial volume. Anesthetic agents generally decrease GFR and urine output. Effects of RBF are variable and probably reflect overall circulatory responses rather than direct actions. All these changes are mild and usually reversed at the end of anesthesia. Positive pressure ventilation depresses renal function through its effects on the central circulation, which can be reversed by administration of fluid or inotropic agents. Controlled hypotensive anesthesia, aortic cross-clamping, and cardiopulmonary bypass represent anticipated renal insults which should be carefully managed.     

Effect of intravenous diazepam on renal function.

The effect of intravenous diazepam on glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) was investigated in 6 children and 12 anesthetized rabbits. A transient decrease in inulin and PAH clearances was observed in 6 children given 4 mg of diazepam intravenously, without measurable change in blood pressure. A similar renal effect was observed in anesthetized rabbits, together with a transient drop in systemic arterial pressure. Continuous infusion of diazepam (5 mg/kg/hr) did not affect renal function in rabbits. We suggest that this effect of diazepam should be borne in mind when the drug is administered to patients undergoing renal clearance studies or to patients with preexistent renal insufficiency.     

血清NT-proBNP水平与代谢综合征相关性研究

目的探讨血清N末端B型钠尿肽原(NT-proBNP)与代谢综合征(MS)的相关性。方法选取该院内分泌科门诊符合MS诊断标准的患者61例为MS组,同时选取同期该院门诊查体健康人群50例为健康对照组。采用电化学发光法测定血清NT-proBNP水平。结果 MS组血清NT-proBNP水平为(112.6±18.6)pg/mL,显著高于健康对照组的(80.3±5.7)pg/mL,差异有统计学意义(P0.05)。血清NT-proBNP与静脉空腹血糖水平(FPG)、腰臀比(WHR)、收缩压(SBP)和三酰甘油(TG)呈正相关(r分别为0.710、0.626、0.595、0.595,P0.05);血清NT-proBNP与高密度脂蛋白胆固醇(HDL-C)呈负相关(r=-0.745,P0.05)。结论血清NT-proBNP与MS密切相关,血清NT-proBNP水平可作为评估MS患者早期预防高危因素的标志物之一。     

慢性心力衰竭患者肾功能变化与NT-proBNP的关系

目的探讨慢性心力衰竭患者(CHF)肾功能变化与血N端脑钠肽(NT-proBNP)浓度的关系。方法对本院125名慢性CHF患者进行血肌酐(CR)、胱抑素C(Cys C)以及NT-proBNP测定,并对血CR、Cys C浓度与NT-proBNP的关系进行比较分析。结果血CR、Cys C异常变化均能引起NT-proBNP显著性的改变,差异有统计学意义(P<0.05),而且血Cys C比CR更能引起NT-proBNP的显著性变化,差异有统计学意义(P<0.05)。结论慢性CHF肾功能变化与心功能有密切相关,而且Cys C更能反应慢性CHF患者肾功能早期改变。     

Effect of renal function on the pharmacodynamics of argatroban

BACKGROUND: Argatroban is a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia (HIT). Argatroban is primarily cleared by hepatic mechanisms, with only small amounts of unchanged drug cleared by the kidneys. OBJECTIVE: To assess the effects of renal function on argatroban dose and activated partial thromboplastin time (aPTT). METHODS: Patients treated with argatroban were identified and prospectively screened. Patients with liver dysfunction were excluded from the analysis. Charts and laboratory data were reviewed daily until a therapeutic aPTT was reached or argatroban was discontinued. Data points collected included age, weight, gender, admitting diagnosis, past medical history, indication for anticoagulation, indication for argatroban, initial dose, goal aPTT, titration instructions, liver function tests, serum creatinine (S(cr)), blood urea nitrogen, and estimated creatinine clearance (Cl(cr)). RESULTS: A total of 66 patients were evaluated and 44 met criteria for inclusion. Baseline S(cr) was elevated at 1.5 mg/dL (0.9, 2.3; median 25th, 75th percentile), with an estimated Cl(cr) 40 mL/min/1.73 m(2) (26, 74). The median dose of argatroban to reach the predefined therapeutic range was 1 microg/kg/min (0.68, 2), with a corresponding aPTT of 60 seconds (54, 66). After univariate analysis, Cl(cr) significantly predicted the therapeutic dose (coefficient b +/- SE 0.019 +/- 0.004; r(2) 0.35; p < 0.001). Covariates that predicted dose were the presence of HIT (coefficient b +/- SE -0.61 +/- 0.3; p = 0.045), history of myocardial infarction (coefficient b +/- SE -0.74 +/- 0.3; p = 0.02), and an indication for anticoagulation of deep-vein thrombosis/pulmonary embolism (coefficient b +/- SE 0.69 +/- 0.3; p = 0.03). CONCLUSIONS: Estimated Cl(cr) significantly predicted the dose of argatroban needed to reach a therapeutic aPTT.     

Effect of cimetidine on renal function in normal man

To evaluate the effect of acute histamine H2-receptor blockade on renal function, renal function studies were performed in a control state and after cimetidine. Studies included acid excretion in response to acid loading, bicarbonate reabsorption during bicarbonate infusion, and urinary concentrating ability. Cimetidine produced no significant effect on any of these functions. During bicarbonate infusion, inulin clearance remained constant while creatinine clearance fell, possibly because of an effect on tubular creatinine secretion.     

Effect of tolmetin on renal function and prostaglandin metabolism

The effect of tolmetin on prostaglandin synthesis by minces of rat renal medulla and on prostaglandin cyclooxygenase of rabbit renal medulla was determined in vitro. The effect of tolmetin was compared to the effects of indomethacin and ibuprofen. Pretreatment of rats in vivo with tolmetin, indmethacin or ibuprofen reduced prostaglandin synthesis by minces of renal medulla. Incubation of medullary tissue in medium containing tolmetin or indomethacin also decreased prostaglandin production. Both drugs reduced O2 consumption by prostaglandin cyclooxygenase from rabbit renal medulla. In addition, the effect of tolmetin, indomethacin and ibuprofen on renal blood flow and the intrarenal distribution of renal blood flow was measured in anesthetized dogs. Tolmetin and ibuprofen resemble indomethacin in reducing renal blood flow and in shifting the distribution of renal cortical flow from the inner cortex toward the outer cortex. It is concluded that tolmetin is an effective inhibitor of prostaglandin synthesis and affects renal function in a fashion similar to other prostaglandin synthesis inhibitors.     

Effect of heparin-induced extracorporeal lipoprotein apheresis on renal function

During the course of heparin-induced extracorporeal lipoprotein apheresis, a patient with no prior known renal impairment or proteinuria demonstrated sustained improvement in estimated glomerular filtration rate, commensurate with reduction in serum lipids and creatine phosphokinase levels. Causes and implications of this observation, which was not a priori, are discussed.     

Effect of calcium entry blocker nitrendipine on renal function after renal vascular occlusion

The ability of the Ca entry blocker nitrendipine to improve postischemic renal function was studied in nine groups (n = 70) of rats. After anesthesia, nitrendipine was administered for 15 min through the femoral vein. The dose administered depended on the group. Group 1 (n = 7), the control, received only 0.9% NaCl, group 2 (n = 12) 0.25 mg/kg; group 3 (n = 10) 0.50 mg/kg; group 4 (n = 8) 0.75 mg/kg; group 5 (n = 6) 1.00 mg/kg; group 6 (n = 7) 1.50 mg/kg; group 7 (n = 7) 2.00 mg/kg; group 8 (n = 6) 2.50 mg/kg; and group 9 (n = 7) 3.00 mg/kg. After the administration of nitrendipine, the kidneys were rendered ischemic for one hour by cross-clamping the renal vessels. Comparison of 24-h creatinine clearances for 72 h after reversal of ischemia demonstrated that nitrendipine was capable of providing a degree of protection against renal ischemia and the protective effect was dose dependent (p less than .05).     

中药利肾宝对慢性肾功能衰竭的影响研究

目的观察中药利肾宝对慢性肾功能衰竭（CRF）大白鼠肾功能的影响。方法用腺嘌呤（Adenin）法造大鼠CRF模型,同时给利肾宝灌胃治疗,1次/d,每隔四天将大鼠放入代谢笼中测24h尿量一次,第25d将大鼠处死。取血测血肌酐（Cr）、尿肌酐（Urs）,计算24h肌酐清除率（Cc）;并测血清K^＋、Na^＋、Mg^2＋、Ca^2＋、P的含量;取大鼠肾脏进行大体组织血观察和镜下病理组织学检查。结果7．5g/kg（生药含量1：2）利肾宝与模型对照组比较,血Cr含量下降（P〈0．01）,24h肌酐清除率升高（P〈0．01）,血K^＋降低（P〈0.01）,血Ca^2＋升高（P〈0.01）,血P有降低趋势;肾脏代偿性增大及组织坏死较模型组明显减轻。结论中药利肾宝能增强机体的排毒能力,减轻肾损伤,改善肾功能,能有效的延缓CRF的进展。     

Effect of renal function on the bioavailability of ciprofloxacin.

The effect of renal function on the bioavailability of ciprofloxacin was studied in 21 subjects with measured creatinine clearances ranging from 0 to 8.99 liters/h per 1.73 m2. Each subject received ciprofloxacin, 200 mg intravenously and 750 mg orally, separated by at least 1 week. Serial (12 to 15) blood samples were obtained over 24 to 48 h. Concentrations in serum were assayed by high-pressure liquid chromatography. Area under the curve was calculated by the trapezoidal rule with extrapolation to infinity. Bioavailability was calculated as the ratio between the dose-normalized area under the curve of oral and intravenous administrations. The overall mean (standard deviation) bioavailability observed was 63.4% (14.6%), similar to that observed in those with normal renal function (69.0% [15.7%]). The mean bioavailability in the subgroup of subjects with renal insufficiency was 59.9% (13.3%). The observed range in bioavailability was 33.9 to 91.4%. Linear regression did not reveal a correlation between creatinine clearance and bioavailability. Renal insufficiency does not appear to affect ciprofloxacin bioavailability.     

Effect of age and renal function on cefonicid pharmacokinetics.

Cefonicid (15 mg/kg) was administered intravenously at a constant rate of infusion over 15 min to 10 geriatric patients (mean age, 77 years) and to 4 young subjects (mean age, 35 years). Model-dependent and noncompartmental pharmacokinetic parameters were calculated and found to be congruous; noncompartmental data are reported. Significant differences in the values for area under the curve, mean residence time, total body clearance, and renal clearance were observed between the geriatric and young groups. Mean elimination half-life values were 9.59 and 4.88 h for the geriatric and young groups, respectively. Total body and renal clearances were inversely correlated to age and directly correlated to creatinine clearance. Free fraction was not correlated to albumin concentration but was correlated exponentially to total cefonicid concentration. Despite the prolonged half-life values observed in our geriatric patients, the difference in mean trough concentrations was slight. Daily administration of a 15-mg/kg dose should provide adequate concentrations in serum and should not produce appreciable accumulation in geriatric patients.