Patients with ovarian cancer have elevated (51)Cr-EDTA plasma clearance early post-operatively

Plasma clearance of (51)Cr-EDTA (Clp(EDTA)) is widely used to determine glomerular filtration rate prior to carboplatin based chemotherapy. We have observed that many patients with ovarian cancer have elevated Clp in the early post-operative phase compared to later phases. The purpose of this study was to examine whether this observation reflects a systematic difference. We retrospectively analysed data from 53 patients who had undergone surgery for ovarian cancer. Twenty-six patients had Clp(EDTA) measured early after the operation (mean, 8 days (range, 3-16 days)) (early group), and 27 patients had Clp(EDTA) measured late post-operatively (mean, 32 days (range, 19-48 days)) (late group). Clp(EDTA) values was measured before the first, third and fifth course of chemotherapy. Additionally, age, height, weight, cancer stage, ascites and tumour histology were noted. Mean Clp(EDTA) in the early group was significantly higher than in the late group (104+/-4.4 vs 89+/-3.5 ml.min(-1) per 1.73 m(2); P =0.005). Clp(EDTA) declined significantly in the early group from the first measurement after the operation until measurement before the third course of chemotherapy but remained constant in the late group. Clp(EDTA) was not correlated to ascites, cancer stage or tumour histology. It is concluded that patients with ovarian cancer have significantly higher Clp(EDTA) in the early post-operative phase than similar patients with Clp(EDTA) measured late post-operatively.     

Estimating kidney function during urography. Comparison of contrast medium clearance and simultaneous 51Cr-EDTA clearance

Blood samples were taken from 21 subjects at 2 to 4 hours after simultaneous injection of contrast medium (metrizoate) for urography and 51Cr-EDTA. Clearance calculations were performed using the single injection (single slope) technique. The plasma concentrations of 51Cr-EDTA and contrast medium were measured by gamma counting and X-ray fluorescence analysis, respectively. A good correlation was found between the clearance of 51Cr-EDTA and clearance of contrast medium (r = 0.94).     

Time to complete mixing for the measurement of glomerular filtration rate from single bolus plasma 51Cr-EDTA clearance

BACKGROUND AND METHOD: In the measurement of glomerular filtration rate from the plasma clearance of 51Cr ethylenediamine tetraacetic acid by using the slope-intercept method, the first sample is conventionally taken at 2 h, the time by which it is generally assumed that the clearance curve has reached a single exponential. We examined this assumption by comparing the slopes, alpha 12 and alpha 23, based, respectively, on samples at 2 and 3 h, and at 3 and 4 h. RESULTS: In 421 patient studies in whom the first sample was taken between 110 and 130 min after injection, the mean ratio, alpha 12/alpha 23, was 1.101 (SEM 0.011) which is significantly higher than unity (P<0.001). The relationship between alpha 12/alpha 23 and the slope, alpha 13 (which is a measure of filtration function already indexed for body size) based on all three samples was negative. By modelling the relationship between mixing time and alpha 13 it was shown that this relationship suggests delayed mixing of the indicator throughout its distribution volume and is inconsistent with irreversible binding of indicator to plasma protein. A significant positive association was observed between alpha 12/alpha 23 and age, but this is largely explained by a generally poorer filtration function in the older age group since low levels of alpha 13 theoretically predict a longer mixing time. In 188 patient studies in whom the first sample was taken more than 130 min after injection, the mean ratio, alpha 12/alpha 23, was 1.055 (SEM 0.017) which is still significantly higher than unity (P<0.005) but significantly less than the ratio based on studies in which the first sample was taken at 110-130 min (P<0.02). The ratio alpha 12/alpha 23 still showed a significant relation (positive) with age but not with filtration function. CONCLUSION: This error in the estimation of glomerular filtration rate to which delayed mixing leads will make its greatest impact when using the simplified slope-only technique, but can be minimized by delaying the first blood sample.     

Renal function measured by x-ray fluorescence analysis. A comparison between contrast medium clearance and non-simultaneous 51Cr-EDTA clearance

In twenty-six patients injected with metrizoate during urography, plasma was analyzed for iodine concentration using x-ray fluorescence analysis, and total plasma clearance of contrast medium was calculated. Total plasma clearance of 51Cr-EDTA was also determined, but not simultaneously, in order to find out if the urographic procedure would influence the kidneys to such an extent that the contrast medium clearance value would differ much from the 51Cr-EDTA clearance value. The errors in the method were assessed and the total error of the contrast medium clearance determination was calculated. When comparing 51Cr-EDTA and metrizoate clearance a correlation of 0.94 and a mean ratio of 1.046 (SD 0.138) was found. The assessable errors cannot fully explain the standard deviation, which might indicate a transient change in kidney function related to elements of the urographic procedure such as laxation with possible dehydration and/or the contrast medium dose.     

Measurement of renal function with iohexol. A comparison of iohexol, 99mTc-DTPA, and 51Cr-EDTA clearance

The nonionic iodinated contrast medium, iohexol, introduced for clinical urography, is eliminated from the human organism mainly by glomerular filtration. The aim of this study was to analyze the applicability of iohexol for glomerular filtration rate (GFR) measurement by comparing the plasma clearance of iohexol to the plasma clearance of the traditionally employed substances, chromium-51-EDTA and technetium-99m-DTPA. Iohexol concentration was measured by x-ray fluorescence. To analyze for possible acute effect of iohexol on renal function, additional measurements of 99mTc-DTPA clearance were made prior to the injection of iohexol. In 15 patients having clearance values between 30 and 130 ml/min per 1.73 m2, there were close correlations (r = 0.95-0.98) among iohexol, 51Cr-EDTA, and 99mTc-DTPA clearance. No significant acute renal effect of iohexol was demonstrated. It is concluded that measurement of iohexol clearance provides information about GFR that is as valid as measurements of 51Cr-EDTA and 99mTc-DTPA clearance. Thus, it is possible to perform urography and a determination of GFR using a single injection of iohexol.     

Absolute 24 h quantification of 99Tcm-DMSA uptake in patients with severely reduced kidney function: a comparison with 51Cr-EDTA clearance.

The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance < or = 60 ml.min-1. Eighteen patients (group A: 9 men and 9 women, mean age 55.8 years, range 28-73 years) had EDTA clearance > 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance < 20 ml.min-1 (mean +/- S.D. = 10.2 +/- 6.6 ml.min-1). EDTA clearance correlated well with %DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.     

Revisiting normal 51Cr-ethylenediaminetetraacetic acid clearance values in children

Purpose Normal ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA) clearance values as a function of age were published a number of years ago. These values were based on data from children with a normal left to right ratio and a normal appearance on DMSA scintigraphy, despite the presence of an acute renal infection. At that time, the authors were unaware that hyperfiltration is a common phenomenon in patients with acute renal infection and that their normal values could have been significantly overestimated. The present work therefore aimed to re-appraise these normal values. Methods In a first step, in order to verify the previous results, the same type of population was selected, namely patients with present or past urinary tract infection but normal images and a normal left to right ratio on DMSA scintigraphy. In a second step, the selection was based on patients who had had no recent urinary tract infection. In both series, a single blood sample method was used for the evaluation of ⁵¹Cr-EDTA clearance. Results In the first group of patients, the results obtained were almost identical to those previously published. In the second group of patients, the results were significantly lower: after 2 years of age, the mean GFR value was 104 ml/min/1.73 m² (10th and 90th percentiles 81 and 135 ml/min/1.73 m², respectively), compared with 117 ml/min/1.73 m² in the first group. Conclusion The data of the second group are probably more representative of the true normal GFR values and can be applied to the entire paediatric population.     

Renal and extrarenal clearance of99mTc-MAG3: A comparison with125I-OIH and51Cr-EDTA in patients representing all levels of glomerular filtration rate

This investigation was undertaken in order to determine whether the clearance of technetium-99m mercaptoacetyltriglycine (^99mTc-MAG₃) is more closely correlated to the clearance of iodine-125 orthoiodohippurate (¹²⁵I-OIH) than to the clearance of chromium-51 ethylene diamine tetra-acetate (⁵¹Cr-EDTA) and whether there is a clinically significant extrarenal clearance of^99mTc-MAG₃ . Fifty-one patients with a glomerular filtration rate (GFR) of 4–132 ml/min were studied. After a simultaneous single injection of the three tracers, plasma clearance was measured from blood samples 0–5 h post injection (p.i.) (0–24h in patients with GFR<15 ml/min). Renal plasma clearance was measured 0–5 h p.i. The ratio between the renal plasma clearance of^99mTc-MAG₃ and¹²⁵I-OIH was 0.57. The ratio between the renal plasma clearance of^99mTc-MAG₃ and⁵¹Cr-EDTA was 2.57. The coefficient of variation (CV) of the^99mTc-MAG₃/¹²⁵I-OIH ratio was significantly smaller than the CV of the^99mTc-MAG₃/⁵¹Cr-EDTA ratio (13.4% versus 31.2%). The corresponding plasma clearance ratios were 0.59 (CV=14.8%) and 2.48 (CV=27.0%). Plasma clearance overestimated renal plasma clearance by 7.0 ml/min (5.4%) for^99mTc-MAG₃ and by 4.1 ml/min (8.4%) for⁵¹Cr-EDTA. The difference in plasma and renal plasma clearance of¹²⁵I-OIH of 5.5 ml/min did not reach statistical significance. Red blood cell binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 2.0%, 14.6% and 0.2%, respectively. Protein binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 86.3%, 61.1% and 5.9%, respectively. The volume of distribution of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 16.3%, 27.0% and 19.4% of body weight. In conclusion, the clearances of^99mTc-MAG₃ and¹²⁵I-OIH are more closely correlated than is the clearance of^99mTc-MAG₃ with GFR. Extrarenal clearance of^99mTc-MAG₃ is relatively smaller than extrarenal clearance of⁵¹Cr-EDTA. Thus, plasma clearance of^99mTc-MAG₃ can be used as a measure of renal tubular function.     

Estimation of normal chromium-51 ethylene diamine tetra-acetic acid clearance in children

In order to estimate the normal range of chromium-51 ethylene diamine tetra-acetic acid (EDTA) clearance in children, we selected a series of 256 patients with past or present urinary tract infection who showed, at the time of the clearance determination, normal technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy and normal left to right DMSA relative uptake. The clearance was calculated by means of either the simplified second exponential method or the 120-min single blood sample; Chantler's correction was used in order to correct for having neglected the first exponential. There was a progressive increase in clearance from the first weeks of life (mean value around 1 month: 55 ml/min/1.73 m²), with a plateau at around 18 months. Between 2 and 17 years of age, the clearance values remained constant, with a mean value of 114 ml/min/1.73 m² (SD: 24 ml/min); this is similar to the level described for inulin clearance. No significant differences were observed between boys and girls, or between clearance values calculated with one or with two blood samples. Taking into account the hour of intravenous injection of the tracer, we did not observe any influence of the lunchtime meal on the distribution of the ⁵¹Cr-EDTA clearance values.     

Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children

BACKGROUND: 51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) in children and adults. AIM: To produce paediatric reference data for use with the British Nuclear Medicine Society (BNMS) GFR guidelines. METHODS: This was a retrospective study of children and adolescents, aged 0-17 years, undergoing combined 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy and GFR examination. GFR was evaluated from Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h according to the methods set out in the BNMS GFR guidelines. 99mTc-DMSA images were reviewed to identify children with normal scans. RESULTS: Of the 45 children having a combined 99mTc-DMSA and GFR investigation, 27 (12 females, 15 males) had a normal scan result. The mean GFR (standard deviation) in the 24 subjects aged 2-17 years was 109.5 (16.8) ml . min(-1) . (1.73 m2)(-1). This compared with a predicted figure of 107.0 (17.0) ml . min(-1) . (1.73 m2)(-1) when the paediatric reference range published by Piepsz et al. was adjusted to be consistent with the BNMS GFR guidelines. When the GFR results in the present study were calculated according to the single-sample and two-sample methods used by Piepsz et al., there was close agreement with the results obtained in the latter study [116.7 (24.2) vs. 114.7 (25.8) ml . min(-1) . (1.73 m2)(-1)]. Children with abnormal 99mTc-DMSA scans had significantly lower GFR than those with normal scans (P=0.003). CONCLUSION: There is a consistent difference between the GFR results in children with normal 99mTc-DMSA scans obtained in the present study and the unadjusted results of Piepsz et al. that can be explained by the different methods of calculating GFR in the two studies. Given the larger number of children in the latter study, it is proposed that centres evaluating GFR according to the BNMS method should adopt the Piepsz et al. reference range adjusted for consistency with the BNMS guidelines. This gives a mean GFR (SD) in children of 2 years and over of 107 (17) ml . min(-1) . (1.73 m2)(-1).     

Conventional measurements of GFR using <Superscript>51</Superscript>Cr-EDTA overestimate true renal clearance by 10 percent

It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid ((51)Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that (51)Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of (51)Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45-79 years) were injected with 3 MBq (51)Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0-2 h and 2-4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean (51)Cr-EDTA total plasma clearance was 84 ml/min (range 50-132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3- and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, alpha(0), and the residual urine volume, delta V. The results were alpha(0)=0.910 (95% CI: 0.889-0.932) and delta V=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of (51)Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using (51)Cr-EDTA overestimate the true renal clearance of tracer by approximately 10%.     

Height of normal pituitary gland on MR imaging: age and sex differentiation

Measurement of the pituitary height was performed on magnetic resonance (MR) images of 213 subjects with no known or suspected pituitary and/or hypothalamic disorders. Midsagittal, T1-weighted images were used for measurements and mean heights in each age and sex group were obtained. In the 10 to 69 year range, the pituitary heights were greater in females than in males. The groups of 0-9 years of both genders showed the minimum mean pituitary height. The maximum of the mean height was observed in the 10 to 19 year age groups of both genders. The height gradually decreased with increasing age after age 20 years. There were no subjects with a height of greater than or equal to 9.0 mm in females or greater than or equal to 8.0 mm in males. There was a marked discrepancy between MR and autopsy findings in the older subjects, probably related to the upward concavity that is often encountered in the aged gland. Because of this concavity, the midsagittal MR measurement will induce underestimation of the whole gland.     

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.     

Prospective validation of single plasma sample 99mTc-ethylenedicysteine clearance in adults.

99mTc-L,L-ethylene, L, dicysteine (EC) clearance shows strong correlation with orthoiodohippurate clearance, and it is possible to estimate effective renal plasma flow from 99mTc-EC clearance. In routine clinical studies, it is practical to use the one or two plasma sample method instead of multiple plasma samples for clearance determination. A single-sample technique was developed for 99mTc-EC, and a regression formula was generated. A prospective study tested the validity of this regression formula. METHODS: The study population was composed of 26 patients with a wide range of renal function. Multiple plasma sample 99mTc-EC clearances were calculated from all patients using the open two-compartment model. Single plasma sample clearances were also determined from the 54-min plasma sample using the regression formula published previously. RESULTS: The multiple-sample plasma clearance of 99mTc-EC ranged from 46 to 668 mL/min with a mean of 300.76 +/- 150.73 mL/min. The clearances obtained from the 54-min plasma sample ranged from 49 to 699 mL/min, with a mean of 297.39 +/- 152.23 mL/min. There was an excellent correlation between the clearances obtained by the two techniques (r = 0.99, slope = 0.9911). The standard error of estimation was found to be 25.9 mL/min. CONCLUSION: This study suggests that 99mTc-EC clearance can be estimated from 54-min plasma samples with an acceptable error of estimation for most routine clinical studies.