Relation between invasive hemodynamics and measured glomerular filtration rate by 51Cr-EDTA clearance in advanced heart failure

The interaction between hemodynamics and kidney function in heart failure (HF) is incompletely understood. We investigated the association between invasive hemodynamic parameters and measured glomerular filtration rate (mGFR) by plasma clearance of 51-chromium-labeled ethylenediamine tetra-acetic acid (⁵¹Cr-EDTA) in patients with advanced HF and tested the hypothesis that patients with reduced mGFR have lower cardiac index (CI) and mean arterial pressure (MAP) as well as higher central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). We retrospectively studied 242 patients (mean age 50?±?13?years) referred for evaluation for heart transplantation or implantation of a left ventricular assist device with a left ventricular ejection fraction < 45% on optimal medical therapy, who underwent right heart catheterization (RHC) and measurement of ⁵¹Cr-EDTA clearance. Mean mGFR was 63?±?21?mL/min/1.73 m², CI was 2.3?±?0.7?L/min/m², PCWP was 21?±?9?mmHg, and CVP was 10.3?±?5.2?mmHg. Univariate analysis demonstrated a significant correlation between mGFR and CI (r² = 0.030, p?=?.007) and CVP (r² = 0.017, p?=?.049) but not between mGFR and MAP or PCWP. In multivariate analyses, none of the hemodynamic variables remained significantly associated with mGFR. While CVP and CI were correlated with mGFR in univariate analysis the results of analyses adjusted for multiple covariates suggest that hemodynamics are only correlated to renal function in advanced HF to a modest degree challenging the hypothesis that renal dysfunction in HF mainly is a consequence of renal congestion.     

51Cr-EDTA clearance determined by one plasma sample in children

Summary. ⁵¹Cr-EDTA clearance was determined in 50 children from the activity in one plasma sample by means of two methods. The calculation of ⁵¹Cr-EDTA clearance by method I (Cl_I) was based on a transformation of the biexponential time-activity curve into a monoexponential with identical area below the time-activity curve. The calculation of ⁵¹Cr-EDTA clearance by method II (Cl_II) was based on a close relation between ⁵¹Cr-EDTA clearance and the reciprocal apparent volume of distribution normalized with respect to body surface area. It was demonstrated that the two methods were closely related. To test the accuracy of the two methods, the results of Cl_I and CI_II, were compared to ⁵¹-EDTA clearance calculated by means of a standard, multiple plasma sample method (Cl_SM). The correlations between Cl_SM and Cl_I, and between and Cl_II were almost identical (r= 0·993 and r = 0·992). The accuracy of ⁵¹Cr-EDTA clearance calculated as Cl_I and Cl_II did not differ significantly from each other.     

肾小球滤过率的估算及其临床应用

目的评估肾脏病改变饮食试验（MDRD）方程在中国糖尿病人群中的临床适用性。方法使用^99mTc-DTPA直接检测463例（女219例，男244例，年龄14—88岁）中国糖尿病人群的肾小球滤过率（GFR），并检测其血清肌酐（Scr）及半胱氨酸蛋白酶抑制剂（Cys C）浓度。以MDRD方程为基础与直接检测GFR比较，评估其在中国糖尿病人群中适用性，估算人种调整系数并与MDRD方程、国内改良MDRD方程比较；了解Scr及Sys C方法学因素对于估算GFR的影响；尝试建立以Cys C为基础的GFR估算公式；比较Scr及Cys C的临床适用性。结果Scr及Cys C检测值倒数与放射性核素测量GFR检测值呈线性关系（r=0．69；r=0．83）；Scr估算方程为GFR[ml·（min·1．73m^2）^-1]=175×（Scr）^-1.154×（age）^-0.203×0．742（女性）×0．827（0．827为中国人群的人种系数）。含此系数的MDRD公式估算GFR的临床诊断性能曲线（ROC曲线）下面积0．818，优于文献报道的MDRD方程（0．644）及国内改良MDRD方程（0．709）。散射法检测Cys C估算方程为GFR[ml·（min·1．73m^2）^-1]=63．24×（Cys C）^-0.3378；透射法检测Sys C估算方程为GFR[ml·（min·1．73m^2）^-1]=59．02×（Cys C）^-0.3880。使用Cys C估算GFR在60岁以上人群优于Scr估算的GFR（ROC曲线下面积0．722与0．583）。方法学差异影响GFR估算，罗氏酶法Scr检测试剂结果可溯源至同位素稀释质谱法（IDMS），明显低于苦味酸法Scr检测（Y=0．94X-0．02）。如使用未溯源至IDMS的苦味酸法Scr试剂，应将方法学系数调整为186。结论临床实验室报告估算GFR值，可使用Scr或Cys C抑制剂。使用Scr估算GFR应使用可溯源至IDMS的肌酐检测结果，并考虑人种因素。     

51Cr-EDTA plasma clearance in severe renal failure determined by one plasma sample

Two hundred and thirty-four measurements of standard 51Cr-EDTA plasma clearance were made in 50 patients with severe chronic renal failure. Based on these data two calculation methods were attempted using one plasma sample drawn 24 h after injection of 51Cr-EDTA. One of the methods used the 'one sample clearance' formulas disregarding exact time of plasma sampling. This method might provide values 3.1 ml/min below or 2.9 ml/min above the established method of total 51Cr-EDTA plasma clearance, and would thus provide insufficient agreement. In the other method an estimate of plasma activity at zero-time was derived from injected dose and body surface area. This method might provide values 1.5 ml/min below or 0.8 ml/min above the established method of 51Cr-EDTA plasma clearance, which would be acceptable for clinical purposes. It is concluded that exact plasma clearance of 51Cr-EDTA in severe renal dysfunction (estimated clearance values below 21 ml/min) may be determined with adequate precision by one plasma sample drawn at 24 h after injection of the tracer without sampling at 5 h. This appears to be a very practical simplification.     

Determination of glomerular filtration rate using iohexol clearance and capillary sampling

Glomerular filtration rate can be conveniently quantified by monitoring the plasma clearance of iohexol. In this study we have evaluated the possibility of further simplifying the investigation by using capillary sampling. Eight women and two men were given a single injection of iohexol (5 ml Omnipaque). Three to 4 h after the injection plasma and capillary samples were taken. Iohexol concentrations in whole blood and in plasma were measured by high-performance liquid chromatography after precipitation with perchloric acid. Iohexol in blood was quantitatively distributed to the plasma compartment. Plasma concentrations of iohexol calculated from the capillary blood concentration and erythrocyte volume fraction were in good agreement with actual plasma concentrations (r = 0.98). The imprecision of iohexol determination in capillary samples was 3.5% (CV) and clearance measurements using venous and capillary sampling also agreed well.     

不同肾小球滤过率预估公式的评价

目的 将四个研究团队(Macisaac、Perkins、Rule、Stevens)的Cys C为变量估算肾小球滤过率(eGFR)公式,与以肌酐为变量之一的简化肾脏病膳食改善方程(MDRD)比较,在2型糖尿病人群肾脏损害各个阶段中,单独或联合应用,是否更能改进eGFR的准确性.方法 检测213例2型糖尿病患者的血清肌酐和Cys C,并运用六个不同的公式作eGFR.结果 六个预估公式均呈正态分布;在GFR的五个临床分期中,均数间多重比较,1、2、3期差异有统计学意义(P＜0.01);以MDRD方程为基准,比较以Cys C为变量的五个估算公式,1、2期Perkins和Macisaac的预估公式值大于MDRD值,3期中Steven的2个估算公式值接近.结论 2型糖尿病人群不同GFR临床分期,基于Cys C和Cr所作预估公式间有不同变化,相同趋势,两者可以互相参考和补充;在1、2期中,Cys C预估公式可能优于Cr.建议在标准化Cys C检测的基础上,扩大研究人群,建立全段和各个分期内eGFR的预估公式.     

糖尿病患者肾小球滤过率评估方法的临床应用研究

目的探讨适用于2型糖尿病患者肾脏功能评估的肾小球滤过率(GFR)估算公式,比较简化肾脏病膳食改善试验(MDRD)、推荐的肾脏病膳食改善试验(rMDRD)、慢性肾脏病流行病学协作组(CKD-EPI)和半胱氨酸蛋白酶抑制剂C(Cys C)相关GFR 4个GFR估算公式的实际应用。方法收集178例2型糖尿病患者的相关资料,检测血清肌酐(SCr)及Cys C浓度,同时行同位素99m锝-二乙三胺五乙酸(99mTc-DTPA)肾动态显像,得出同位素GFR(iGFR),并以此作为GFR的参考标准。依据美国糖尿病协会(ADA)标准将178例患者分成3个亚组[GFR 15～59、60～89、≥90 mL/(min·1.73 m2)],对各公式的GFR估算值(eGFR)与iGFR进行配对t检验、相关分析、Bland-Altman分析、受试者工作特征(ROC)曲线及15%、30%、50%符合率比较。结果 MDRD公式应用于GFR<60 mL/(min·1.73 m2)的患者,其eGFR与iGFR相关性较好,符合率较高,偏差无统计学意义;应用于GFR≥60 mL/(min·1.73 m2)的患者,其eGFR与iGFR差异有统计学意义(P<0.001)。rMDRD公式计算eGFR在准确性、诊断效能等方面与MDRD公式无明显差异。CKD-EPI公式应用于GFR≥90 mL/(min·1.73 m2)的患者,其eGFR与iGFR的符合率高于MDRD和rMDRD;应用于GFR 60～89 mL/(min·1.73 m2)的患者时,其符合率低于Cys C GFR公式。Cys C GFR公式得出的eGFR与iGFR的相关性、偏差、一致性及符合率均明显优于MDRD和rMDRD公式,尤其应用于GFR≥90 mL/(min·1.73 m2)的患者时,其eGFR与iGFR偏差无统计学意义,明显优于其他3个公式。结论 4个GFR估算公式均能准确估算GFR<60 mL/(min·1.73 m2)的2型糖尿病患者的肾功能水平。在GFR≥90 mL/(min·1.73 m2)时,Cys C GFR公式明显优于传统以SCr为基础的GFR估算公式。     

Measurement of glomerular filtration rate in adults: accuracy of five single-sample plasma clearance methods

Summary. After an intravenous injection of a tracer that is removed from the body solely by filtration in the kidneys, the glomerular filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of urine is not needed. In the present investigation the total plasma clearance of ⁵¹Cr-EDTA (ethylenediaminetetra-acetate) was assessed from 13 blood samples taken 5–300 min post-injection in 44 adult patients with GFR>15 ml min^-1. In 34 of these patients the plasma clearance of ⁹⁹Tc^m-DTPA (diethylenetri-aminepenta-acetate) was determined simultaneously. Using these clearance values as reference the accuracy of six simplified methods were studied: five single-sample methods and one five-sample method. The standard error of estimate (SEE) of the single-sample methods ranged from 4·2 to 7·5 ml min^-1 using EDTA, and from 3·8 to 6·3 ml min^-1 using DTPA. SEE of the five-samples method was 3·0 ml min^-1 (EDTA) and 3·1 ml min^-1 (DTPA). The single-sample methods given by Christensen & Groth (1986) and by Tauxe (1986) are recommended for daily use, as SEE was small even at low GFR values. In patients with GFR < 80 ml min^-1, in whom a highly accurate determination is needed, a multiple samples method is recommended, e.g., Brøchner-Mortensen (1972).     

Total plasma clearance versus urinary plasma clearance of 51Cr-EDTA in patients with cirrhosis with and without fluid retention

Abstract

Background and aim. In patients with fluid retention, the total plasma clearance of ⁵¹Cr-EDTA (Cl_P) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare Cl_P with the urinary plasma clearance of ⁵¹Cr-EDTA (Cl_U) in patients with cirrhosis with and without fluid retention. Material and methods. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of ⁵¹Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. Cl_P was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. Cl_U was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between Cl_P and Cl_U (Cl_P ? Cl_U = Cl_Δ) was mean 4.5 mL/min/1.73 m². In patients with ascites, Cl_Δ was significantly higher (17.6 mL/min/1.73 m², p < 0.0001). Cl_Δ increased with lower values of GFR (r = ? 0.458, p < 0.001). Repeated measurements of Cl_U in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with Cl_P, except for higher clearance values, which were somewhat underestimated by the former. Conclusion. In patients with fluid retention and ascites Cl_P and corrected one-pool clearance overestimates GFR substantially. Although Cl_U may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.     

Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients.

OBJECTIVE: The aim of this preliminary investigation was to evaluate the use of aminoglycoside serum concentrations as a surrogate measure of the glomerular filtration rate (GFR) in comparison with other measured and empiric methods against inulin, the criterion standard measure of GFR. DESIGN: A consecutive sample of all eligible patients. SETTING: An eight-bed medical intensive care unit in a university-affiliated tertiary-care teaching hospital. PATIENTS: Ten critically ill medical patients receiving gentamicin or tobramycin for presumed or documented gram-negative bacillary infection were enrolled in the study. The patients were mechanically ventilated and had underlying organ system dysfunction. All ten patients completed the study. INTERVENTION: Patients underwent renal functional assessment by measured inulin (Cl(in)) and 24-hour urinary creatinine clearance (Clcr). Aminoglycoside serum concentrations were used to estimate GFR and were compared with the two measured methods and a creatinine clearance calculated with the Cockcroft-Gault method (ClCG). All evaluations were performed the same day. RESULTS: Cl(in) averaged 51.6 +/- 35.0 mL/min and serum creatinine ranged from 0.3 to 5.4 mg/dL (26.5 to 477.3 mumol/L). Steady-state peak and trough aminoglycoside concentrations were 6.1 +/- 1.4 and 1.3 +/- 0.9 micrograms/mL, respectively. There were no statistically significant differences between the various methods, although the aminoglycoside-calculated GFR (Cl(amg)) 95 percent confidence intervals were smaller than Clcr and ClCG compared with Cl(in). Mean absolute errors were smaller with Cl(amg) than with Clcr and ClCG. Regression results indicated that only Cl(amg) and ClCG demonstrated agreement with Cl(in) (lines not different from y = x). However, the Cl(amg) showed closer agreement, with a mean square error almost half that of ClCG (9.6 vs. 18.1). CONCLUSIONS: Cl(amg) can be used routinely as an estimate of GFR in critically ill patients, with less error than empiric methods.     

对2型糖尿病患者肾小球滤过功能的评价

目的评价临床上常用的测定肾小球滤过率（GFR）的指标在2型糖尿病患者的适用性。方法2型糖尿病患者60例，以体表面积标准化的双血浆法^99Tc^m-DTPA血浆清除率测定值（rGFR）作为测定GFR的参考指标，比较血肌酐（Scr）、肌酐清除率（Ccr）、^99Tc^m-DTPA肾动态显像法（gGFR）、基于Scr的GFR评估方程7（MDRD 7）以及血清半胱氨酸蛋白酶抑制剂C（cystatin C，Cys C）等多种方法与rGFR的相关性，测定上述方法在反映2型糖尿病患者肾功能减退的特异性和敏感性，用受试者工作特征曲线（ROC）评价上述指标检测肾小球滤过功能的准确性。结果2型糖尿病患者60例，其中男35例，女25例，年龄（62．4±11．7）岁，病史（10．66±9．35）年，Scr、Ccr、gGFR、MDRD 7及Cys C测定结果均与gGFR呈显著相关（r分别为-0．500、0．675、0．367、0．428及-0．588，P均〈0．001），其中Ccr与rGFR值相关性最好，其次为Cys C。Ccr、MDRD方程7及Cys C在判断GFR下降时的敏感度较高（分别为82．1％、85．7％及85．7％），显著高于Scr及gGFR方法（10．7％及46．6％，P〈0．01）；Scr在判断GFR下降时的特异度为100％，显著高于MDRD方程7的特异度（25．0％，P〈0．01）。Cys C和Ccr的受试者工作特征曲线（ROC）下面积显著高于Scr，MDRD方程7和gGFR。Cys C的最佳判定域值为1．18mg／L，该域值的敏感度和特异度分别为80％和57．5％；Ccr的最佳判定域值为62ml／min，该域值的敏感度和特异度分别为90％和67．9％。结论Ccr和Cystatin C能够较理想地反映2型糖尿病患者GFR的变化。     

Lopromide one-sample clearance as a measure of glomerular filtration rate

Objective: The pharmacokinetics of iopromide were analysed using a two‐compartment model. The optimal point of time for blood withdrawal for calculation of a one‐sample clearance was determined. Methods: Plasma concentration of iodine was measured up to 8 h postinjection (p.i.) in 62 adult patients who received 120 ml iopromide for computed tomography (CT). A two exponential function was fitted by a weighted least error square method. As reference method, clearance was calculated from this function and the injected amount of iodine. Empirical parameters for calculation of one‐sample clearance were determined. This one‐sample clearance was compared with one‐sample clearance calculated according to formulas developed for Tc99m‐DTPA by Jacobsson as well as a two sample method. Results: Total distribution volume of iopromide was calculated as 0·242 Lkg^?1± 5·9%. A high correlation of all one‐sample method and the two‐sample method with reference to clearance was found. Best estimation of iopromide plasma clearance was achieved by determining one‐sample clearance 270 or 285 min p. i. with SD_y.x of 5·8 ml min^–1. Conclusions: After administration of 120 ml iopromide, one‐sample plasma clearance can be calculated with low estimation error taking one blood sample at an appropriate time point. Late phase pharmacokinetics of iopromide found in the present study showed to be virtually identical to results published for iohexol and Tc99m‐DTPA.     

Screening of kidney function by plasma creatinine and single-sample 51Cr-EDTA clearance determination--a comparison

Nomograms or simple formulas have been suggested for estimating the glomerular filtration rate (GFR) from either plasma creatinine (ClK) or from a single plasma sample drawn after an intravenous injection of 51Cr-EDTA (ClA/B). This study compares the precision of estimating GFR as ClK and ClA/B. A multiple plasma-sample standard method (ClSM) served as reference. The comparison was performed in 136 individuals. The variance of ClA/B on ClSM was 14.4 ml/min/1.73 m2 while the variance of ClK on ClSM was 204.5 ml/min/1.73 m2. It is concluded that the ClA/B values are more precise than the ClK values (p less than 0.01). The single-sample method for determination of 51Cr-EDTA clearance seems well-suited for evaluation and monitoring of patients with known or suspected kidney diseases. It may even be applied for screening purposes in cases where plasma creatinine would otherwise have been chosen instead of the usual resource-demanding method for determination of ClSM.     

糖尿病肾病的研究进展

糖尿病肾病 (diabeticnephropathy ,DN)是糖尿病的一种严重血管并发症 ,是目前引起糖尿病患者死亡的主要原因之一。但其发病机制至今还未完全明了 ,本文总结近年来这方面的研究发现DN的发病与氧化应激的诱导、遗传易感因素、肾小球细胞外基质堆积、多种细胞因子如TGF β表达过多、GH IGF轴发生紊乱、ICAM 1水平升高、糖基化末端产物 (AGEs)产生过多、血小板衍化微粒 (PMP)及活化血小板促进血小板黏附聚集 ,导致肾动脉硬化等诸多因素有关。     

胱抑素C在糖尿病性肾病中评估肾小球滤过率的价值研究

目的比较不同阶段2型糖尿病肾病患者血清胱抑素C(CysC)水平,探讨相关性。方法将柳州医学高等专科学校第一附院收治的2型糖尿病患者148例,按内生肌酐清除率Ccr值分为三组,测定各组CysC水平、血肌酐(Scr),计算内生肌酐清除率(Ccr)、C-G公式计算的肾小球率过滤(CG-GFR)。结果研究组各组间血清胱抑素C有显著差异。以Ccr 90ml/(min.1.73m2)或60ml/(min.1.73m2)为切点作ROC曲线,三者之中,CysC对Ccr的诊断效能最强,CG-GFR次之,血肌酐最弱。结论血清CysC水平的升高与糖尿病肾病密切相关,CysC比血肌酐、CG-GFR可更敏感地评估早中期肾功能损害的改变。     

Soybeans ameliolate diabetic nephropathy in rats

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented.     

86例1型糖尿病血脂与糖尿病肾病的关系

目的探讨血脂和脂蛋白代谢的改变与1型糖尿病肾病的关系。方法将86例1型糖尿病患者参照Mogensen关于糖尿病肾病（DN）分类标准,分为DN组（65例）和糖尿病无肾病组（21例）,根据尿白蛋白排泄率（UAER）及血肌酐水平将DN又分为三个亚组,分为早期肾病组（n=28）,临床肾病组（n=23）和晚期肾病组（n=14）。观测患者血糖、胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和脂蛋白A（ApoA）、脂蛋白B（ApoB）变化。结果与糖尿病无肾病组比较,DN组血清甘油三酯、低密度脂蛋白胆固醇（LDL—C）水平升高（P〈0．05或P〈0．01）;DN三亚组之间血脂、载脂蛋白随着DN程度加重而升高,差异有统计学意义（P〈0．01）;血清甘油三酯、LDL—C、载脂蛋白B水平与UAER、血糖呈正相关（P〈0.01）。结论DN患者存在明显的脂质代谢异常,与血糖控制不良有关,且随着肾脏损害程度加重而加重,高血脂促进DN的发生和发展,糖尿病则加重血脂紊乱,形成恶性循环。