Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure

In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [99mTc] diethylenetriaminepentaacetic acid (DTPA) (UD), [125I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [99mTc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure.     

慢性肾脏病患者肾小球滤过率经验公式比较

目的比较肾脏疾病饮食改良研究方程式(MDRD)、新慢性肾脏疾病流行病学合作研究方程式(CKD-EPI)以及胱抑素C(Cys C)估算公式(eGFR-Cys)对慢性肾脏病(CKD)患者肾小球滤过率(GFR)的预测性能。方法测定93例CKD患者的99mTc-二乙烯三胺戊乙酸(DTPA)血浆清除率(rGFR)作为GFR金标准,另用MDRD、CKD-EPI和eGFR-Cys公式分别计算GFR估测值(eGFR),并将rGFR与3种公式计算的eGFR进行比较。结果相对于rGFR,CKD-EPI公式偏倚为-3.4±10.7ml/(min·1.73m2),eGFR-Cys公式为-4.8±11.9ml/(min·1.73m2),MDRD公式为-5.4±10.4ml/(min·1.73m2),三者间差异均无统计学意义。对于rGFR测定值30%误差范围内GFR估测值的百分率,CKD-EPI公式e、GFR-Cys公式、MDRD公式分别为74.2%7、2.0%和64.5%,差异无统计学意义。当rGFR>60ml/(min·1.73m2)时,CKD-EPI公式30%准确度(75.7%±5.1%)明显高于MDRD公式(54.1%±7.7%,P<0.05)。以放射性核素法的GFR作为标准,以rGFR≤60ml/(min·1.73m2)作为GFR受损标准,进行3种eGFR诊断GFR受损性能的受试者工作特征(ROC)曲线分析,MDRD eGFR的ROC曲线下面积为0.862,CKD-EPI为0.863,eGFR-Cys为0.877,3个曲线下面积的差异无统计学意义。结论 3个公式对GFR的估算能力基本相似。CKD-EPI公式和eGFR-Cys公式是否可以取代MDRD公式尚需进一步研究。     

Comparison of mathematic models for assessment of glomerular filtration rate with electron-beam CT in pigs

PURPOSE: To prospectively compare in pigs three mathematic models for assessment of glomerular filtration rate (GFR) on electron-beam (EB) computed tomographic (CT) images, with concurrent inulin clearance serving as the reference standard. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Inulin clearance was measured in nine pigs (18 kidneys) and compared with single-kidney GFR assessed from renal time-attenuation curves (TACs) obtained with EB CT before and after infusion of the vasodilator acetylcholine. CT-derived GFR was calculated with the original and modified Patlak methods and with previously validated extended gamma variate modeling of first-pass cortical TACs. Statistical analysis was performed to assess correlation between CT methods and inulin clearance for estimation of GFR with least-squares regression analysis and Bland-Altman graphical representation. Comparisons within groups were performed with a paired t test. RESULTS: GFR assessed with the original Patlak method indicated poor correlation with inulin clearance, whereas GFR assessed with the modified Patlak method (P < .001, r = 0.75) and with gamma variate modeling (P < .001, r = 0.79) correlated significantly with inulin clearance and indicated an increase in response to acetylcholine. CONCLUSION: CT-derived estimates of GFR can be significantly improved by modifications in image analysis methods (eg, use of a cortical region of interest).     

Determination of glomerular filtration rate with Visipaque in patients with severely reduced renal function

Iodixanol (Visipaque, Nycomed Imaging AS, Oslo, Norway), an isotomic, dimeric and non-ionic contrast medium (CM), and iohexol (Omnipaque, Nycomed Imaging AS, Oslo, Norway), a low-osmolar, monomeric and non-ionic contrast medium, were used as glomerular filtration rate (GFR) markers in patients with severely impaired renal function. Different methods for determining GFR were compared. A total of 16 patients with s-creatinine > 400 mol/l were enrolled in the study; 8 in each CM group. Serum-iodine was measured, and plasma CM clearance was determined using the Bröchner-Mortensen method, the single-sample method and conventional method. The ratios between the results obtained from the conventional method and each of the two other methods were calculated. These data were plotted against the mean of the pairs compared, and the upper and lower limits of agreement were calculated as the mean ratio ± 2SD. The comparison showed a high degree of agreement between methods, and the two simpler methods seem to be good alternatives to the conventional method, which gave good estimates of GFR (vs that determined by means of renal ¹²⁵I-iothalamate clearance) when 24-h blood samples were included. However, slight overestimations of GFR, due to extrarenal excretion of the CM, were observed. In summary, serum clearance of iodixanol, as determined by the Bröchner-Mortensen method or single-sample method seems to be a simple and accurate marker of GFR in patients with severely reduced renal function. The findings obtained with iodixanol were similar to those obtained with iohexol.Correspondence to: P. Kjærsgaard     

A comparison of simplified and standard methods for the measurement of glomerular filtration rate and renal tubular function

Two methods of measuring the clearance of 99Tcm DTPA, OIH and iothalamate were compared with standard techniques of measuring the clearance rates of inulin and sodium para-aminohippurate. The best correlation was between the clearance of subcutaneously injected radiolabelled iothalamate or 99Tcm DTPA and that of inulin. 99Tcm DTPA and 131I OIH clearances measured by a two blood sample technique did not give as good a correlation with inulin and PAH clearances respectively. When measurements of GFR and tubular function were repeated on the same patients the changes measured by inulin and PAH clearances did not correlate with those measured by the two blood sample technique using 99Tcm DTPA and OIH. Our results suggest that the clearance of subcutaneously injected iothalamate or DTPA can replace inulin clearance measurements. The two blood sample technique of measuring DTPA and OIH clearance does not directly reflect inulin and PAH clearance and is insufficiently reproducible to be used to follow changes in renal function.     

Comparative assessment of techniques for estimation of glomerular filtration rate with 99mTc-DTPA

The relative accuracy of five simplified methods of measuring glomerular filtration rate was prospectively assessed using ^99mTc-DTPA. The slope of the biological clearance curve, the 3-h volume of dilution and three renal tracer uptake methods (Piepsz, Gates and Nielsen) were concurrently compared with a multiple blood sampling reference method. The volume of dilution method from a single blood sample was markedly superior to the other four simplified methods which all had a similar degree of accuracy.     

Comparative assessment of techniques for estimation of glomerular filtration rate with 99mTc-DTPA

The relative accuracy of five simplified methods of measuring glomerular filtration rate was prospectively assessed using 99mTc-DTPA. The slope of the biological clearance curve, the 3-h volume of dilution and three renal tracer uptake methods (Piepsz, Gates and Nielsen) were concurrently compared with a multiple blood sampling reference method. The volume of dilution method from a single blood sample was markedly superior to the other four simplified methods which all had a similar degree of accuracy.     

51Cr-EDTA measurements of the glomerular filtration rate in patients with sickle cell anaemia and minor renal damage

BACKGROUND: Creatinine clearance has been reported to be inaccurate for the estimation of glomerular filtration rate (GFR) in patients with sickle cell anaemia (SCA). Inulin clearance, the reference method for GFR estimation, is impractical for routine use in these patients, and 51Cr-EDTA measurements of the GFR have been rarely reported in this disease. METHODS: In order to obtain reference 51Cr-EDTA values in this disease, we studied 70 patients (40 females; 13-59 years of age, mean: 31.6 years) with homozygous SCA, normal serum creatinine and urinary albumin excretion < or =200 microg x min(-1). All patients were submitted to single-injection 51Cr-EDTA GFR, urinary albumin and haematocrit measurements. 51Cr-EDTA clearances were calculated in different age groups (<20, 20-29, 30-39, 40-49 and >50 years). RESULTS: The mean GFR (+/-standard deviation) obtained for the 70 patients was 111.5+/-23.1 ml x min(-1). Analysis of variance for evaluation of the possible interaction effect between 51Cr-EDTA clearance and sex, age, urinary albumin and haematocrit demonstrated patient age as the only factor influencing 51Cr-EDTA clearance (P < 0.001). The Spearman correlation coefficient showed a significant relationship between 51Cr-EDTA clearance and patient age (r = -0.44, P = 0.0001), but not between 51Cr-EDTA and urinary albumin (r = -0.17, P = 0.1546) or haematocrit (r = 0.079, P = 0.5121). The group aged 20-29 years presented the highest 51Cr-EDTA clearance mean value (126.7+/-20.4 ml x min(-1)), with a progressive reduction in the older groups. CONCLUSION: Young adults with homozygous SCA, normal serum creatinine and micro-albuminuria or normo-albuminuria present supranormal 51Cr-EDTA GFR values. These values rapidly decrease after 30 years of age. We did not find association between urinary albumin and GFR in these patients.     

Simplified estimation of glomerular filtration rate and effective renal plasma flow

A method is described for the determination of GFR and ERPF using a combined injection of ⁵¹Cr-EDTA and ¹²⁵I-iodohippurate. Plasma samples obtained at 60 min and 150 min after administration were used to determine a flow rate F assuming a monoexponential clearance of the tracers. Empirical relationships were found between F and the true GFR and ERPF determined from multiple sampling and multi-exponential analysis of the clearance curves. The method was shown to be superior to previously published methods involving one or two samples. GRF was calculated with a standard deviation (SD) of only 3.3 ml/min when compared to the multiple sample technique (the reference method), whereas the best estimate from a single sample had a SD of 6.3 ml/min. An improvement in accuracy of ERPF estimation was achieved for values of flow of less than 200 ml/min when the SD was only 9.3 ml/min.     

Simplified estimation of glomerular filtration rate and effective renal plasma flow

A method is described for the determination of GFR and ERPF using a combined injection of 51Cr-EDTA and 125I-iodohippurate. Plasma samples obtained at 60 min and 150 min after administration were used to determine a flow rate F assuming a monoexponential clearance of the tracers. Empirical relationships were found between F and the true GFR and ERPF determined from multiple sampling and multi-exponential analysis of the clearance curves. The method was shown to be superior to previously published methods involving one or two samples. GFR was calculated with a standard deviation (SD) of only 3.3 ml/min when compared to the multiple sample technique (the reference method), whereas the best estimate from a single sample had a SD of 6.3 ml/min. An improvement in accuracy of ERPF estimation was achieved for values of flow of less than 200 ml/min when the SD was only 9.3 ml/min.     

Calculation of the renal perfusion and glomerular filtration rate from the renal impulse response obtained with MRI.

The aim of this study was to assess the importance of deconvolution for the calculation of renal perfusion and glomerular filtration rate (GFR) on the basis of concentration-time curves as measured with perfusion MRI. Six rabbits were scanned dynamically after injection of a gadolinium chelate. Concentration-time curves were generated by manually drawing regions of interest in the aorta and the renal cortex. To remove the dependency on the arterial input function, a regularized structured total least-squares deconvolution algorithm was used to calculate the renal impulse response. This curve was fitted by the sum of two gamma variate functions, corresponding to the passage of the contrast agent in the glomeruli and the proximal convoluted tubules. Tracer kinetics models were applied to these two functions to obtain the renal perfusion and GFR. For comparison, these two parameters were also calculated on the basis of the renal concentration-time curve before deconvolution. The renal perfusion values correlated well (r = 0.9, P = 0.014) with the values calculated by a validated upslope method. The GFR values correlated well (r = 0.9, P = 0.014) with the values obtained from the clearance of (51)Cr-EDTA. A comparison of the values obtained with and without deconvolution demonstrated the necessity of deconvolution.     

Reappraisal of single-sample and gamma camera methods for determination of the glomerular filtration rate with99mTc-DTPA

The aim of this study was to assess the clinical validity of single-sample methods and gamma camera uptake methods with 99mTc-DTPA for the estimation of the glomerular filtration rate (GFR). The study was performed in 50 patients with various degrees of renal function (29 males and 21 females; age 27-90 yrs; serum creatinine level 0.34-6.49 mg/dl). As a reference the "true" GFR (GFRt) was determined from plasma clearance by means of the two compartment model curve fitting 10 plasma samples. The GFRt of more than 30 ml/min in 46 patients was compared to the GFR which was estimated with 7 single-sample methods, two gamma camera uptake methods and 24-hour endogenous creatinine clearance (24hCcr). Close correlation was observed in all single-sample methods. The highest linear correlation was observed in the Christensen and Groth's method rewritten by Watson for a 180-min plasma sample (r = 0.991, see = 5.84 ml/min). The smallest random error was observed in the Groth and Aasted's method for a 180-min plasma (r = 0.989, see = 4.31 ml/min/1.73 m2). Our method was lowest in % absolute difference analysis (mean = 4.10%). The gamma camera uptake methods correlated significantly with the GFRt (r = 0.746-0.774), but were less reliable than any of the single-sample methods (see = 15.41 ml/min-19.14 ml/min). The lowest correlation was observed in the 24hCcr (r = 0.698, see = 50.76 ml/min/1.73 m2). The single-sample method was more accurate than the gamma camera method, and the gamma camera method was more accurate than 24hCcr. The single-sample method should be recommended for the accurate determination of the GFR with 99mTc-DTPA in a patient with mild to moderate renal dysfunction.     

Comparison of imaging methods for diagnosing enlarged parathyroid glands in chronic renal failure

Three noninvasive imaging methods, CT, scintigraphy with 201TlCl and 99mTcO4-, and ultrasonography, were performed on 36 patients with chronic renal failure and secondary hyperparathyroidism. The patients subsequently underwent total parathyroidectomy and parathyroid autograft. The detection rates of the three methods for the 143 excised parathyroid glands were compared according to gland weight and location. Computed tomography detected 53.8% of all glands and 77.6% of 76 glands weighing more than 500 mg. Scintigraphy detected 51.0% of all glands and 77.6% of glands heavier than 500 mg. Ultrasonography detected 42.7% of all glands and 65.8% of glands heavier than 500 mg. The detection rate of upper glands was best with CT (53.5 and 87.9%): that of lower glands was best with scintigraphy (62.0 and 78.6%). Although the combination of the three methods diagnosed 66.4% of all glands and 89.5% of glands heavier than 500 mg, CT and scintigraphy, the best two combinations, visualized 64.3 and 88.2%.     

Functional radionuclide imaging of renal mean transit time and glomerular filtration rate

A technique for functional radionuclide imaging of renal mean transit time and glomerular filtration rate from the results of gamma camera renography with a computer is described. The method uses deconvolution analysis on each pixel time-activity curve. The images of both parameters are of good quality except in cases of very low glomerular filtration rate. They effectively summarize the transit and uptake information available from the renogram and should prove a valuable adjunct in its routine analysis.     

Body surface area correction in single-sample methods of glomerular filtration rate estimation

Single-sample methods of estimating glomerular filtration rate (GFR) are used routinely, in a number of institutions, to calculate values of total plasma clearance (TPC), which are then converted to GFR. Adjustment of the final estimate for body surface area (BSA) is not adequate to allow adult equations to be used in children and work has been undertaken to seek an age-independent technique. The aim of this study was to evaluate the ability of an alternative method of correcting for BSA, of scaling the plasma sample activity, to achieve an age-independent solution. The accuracy of the scaled TPC values was compared with a monoexponential analysis as the 'gold' standard. Data from 60 patients were analysed using 16 single-sample models. Patients were chosen so that 10 could be allocated to each of six categories involving three age groups (0-3 years, 4-17 years and 18+ years) and two classes of TPC (< 40 and > 40 ml.min-1). Adjustment of the plasma activity gave more accurate results than correction of the final estimate in 87% of the categories for 15 of the models. This improvement was particularly apparent in the case of adult equations applied to child data, which gave results similar to those obtained using child equations, indicating that they can be used with equal accuracy.