Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.     

Estimation of glomerular filtration rate and technetium-99m diethylene triamine penta-acetic acid using chromium-51 ethylene diamine tetra-acetic acid

Simultaneous measurements of the clearance rate of chromium-51 ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) and technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) were performed in 54 patients with a range of function between 9 and 176 ml/min. Using multiple blood samples the two clearance values correlated well (r = 0.97, SEE 8.6 ml/min) and DTPA clearance was higher by 2.9%. For each radiopharmaceutical the plasma clearance rates obtained using multiple blood samples were compared with those obtained with simplified methods, i.e., the 60–180 min two-sample method of Russell and the mono-exponential method with the Brochner-Mortensen correction. For both radiopharmaceuticals the clearance values correlated well with the Russell method (r = 0.99, SEE = 4.1 ml/min for EDTA;r = 0.99, SEE 4.9 ml/min for DTPA) and the mono-exponential method (r = 0.99, SEE 3.6 ml/min for EDTA;r = 0.99, SEE 3.9 ml/min for DTPA). The mean plasma clearance obtained using multiple blood samples did not differ significantly from that obtained with the Russell method, either in patients with a glomerular filtration rate (GFR)<30 ml/min or in patients with GFR30 ml/min. The mean plasma clearance obtained using multiple blood samples differed significantly from that obtained with the mono-exponential method because of the great difference observed in patients with GFR30 ml/min. It is concluded that the Russell two-sample method after injection of^99mTc-DTPA is accurate enough for routine clinical use.     

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.     

Evaluation of renal function in low-dose cyclosporine-treated patients using technetium-99m diaminocyclohexane: a cationic tubular excretion agent

Technetium-99m diaminocyclohexane (DACH) is a new tubular agent excreted via a cationic transport mechanism, like cyclosporine-A (CsA). It is expected that ^99mTc-DACH will permit effective assessment of tubular function in CsA-treated patients. To establish the pharmacokinetic characteristics of ^99mTc-DACH and to ascertain whether this new agent is useful in CsA-treated patients, 11 healthy volunteers and 15 CsA-treated patients underwent renal imaging and clearance studies using ^99mTc-DACH and chromium-51 ethylene diamine tetra-acetic acid (EDTA). ^99mTc-DACH yielded satisfactory dynamic renal images in all participants. The mean plasma clearance of ^99mTc-DACH was significantly greater than that of ⁵¹Cr-EDTA in volunteers (109.4±19.7 ml/min versus 86.6±13.7 ml/min, P<0.05). However, the urinary excretion of ^99mTc-DACH at 90 min was significantly lower than that of ⁵¹Cr-EDTA (46.1%±9.3% versus 53.1%±8.6%, P<0.05), most probably due to its partial parenchymal retention. The elimination half-life of ^99mTc-DACH was significantly increased in CsA-treated patients in comparison to volunteers, and consequently the plasma clearance values were significantly suppressed in these patients, in contrast to ⁵¹Cr-EDTA and endogenous creatinine clearance values. In conclusion, our findings indicate that ^99mTc-DACH, as a sensitive marker of cationic tubular function, could be used to monitor renal haemodynamics in patients receiving CsA treatment. Received 19 June and in revised form 28 July 1998     

Estimation of chromium-51 ethylene diamine tetra-acetic acid plasma clearance: a comparative assessment of simplified techniques

Chromium-51 ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) total plasma clearance was evaluated using a multi-sample method (i.e. 12 blood samples) as the reference compared with several simplified methods which necessitated only one or few blood samples. The following 5 methods were evaluated: terminal slope-intercept method with 3 blood samples, simplified method of Bröchner-Mortensen and 3 single-sample methods (Constable, Christensen and Groth, Tauxe). Linear regression analysis was performed. Standard error of estimate, bias and imprecision of different methods were evaluated. For ⁵¹Cr-EDTA total plasma clearance greater than 30 ml · min^–1, the results which most approximated the reference source were obtained by the Christensen and Groth method at a sampling time of 300 min (inaccuracy of 4.9%). For clearances between 10 and 30 ml · min^–1, single-sample methods failed to give reliable results. Terminal slope-intercept and Bröchner-Mortensen methods were better, with inaccuracies of 17.7% and 16.9%, respectively. Although sampling times at 180, 240 and 300 min are time-consuming for patients, ⁵¹Cr-EDTA total plasma clearance can be accurately calculated for values greater than 10 ml · min^–1 using the Bröchner-Mortensen method. In patients with clearance greater than 30 ml · min^–1, single-sample techniques provide a good alternative to the multi-sample method; the choice of the method to be used depends on the degree of accuracy required. Offprint request to: G. Picciotto     

Technetium-99mL,l-ethylenedicysteine clearance and correlation with iodine-125 orthoiodohippurate for the determination of effective renal plasma flow

Technetium-99mL,l-ethylenedicysteine (^99mTcL,l-EC) is a new renal tubular tracer that allows the determination of the effective renal plasma flow (ERPF). The aim of this study was to derive simplified methods for the estimation of^99mTc-L,l-EC clearance using one or two plasma samples after bolus injection. Fifty-nine multiple plasma dual-tracer samples (nine samples from 5 to 120 min after injection) were obtained after injection of kit-formulated^99mTc-L,l-EC and iodine-125 orthoiodohippurate (01H). The studies were performed in 25 stable and 24 unstable transplant recipients, in five patients with renal insufficiency (four on chronic haemodialysis) and in five normal volunteers. This allowed a wide range of renal function values to be covered, with ERPF (estimated by 01H clearance) ranging from 25.4 to 604.0 ml/min. The reference^99mTc-L,l-EC clearance, as calculated from the multisample model, could be estimated from two samples at 15 and 90 min with an error of 11.3 ml/min and from one sample at 90 min with an error of 17.8 ml/min. Using appropriate linear regression analysis, ERPF could be estimated by the two- and one sample^99mTc-L,l-EC clearance with an error of 24.2 and 22.8 ml/min, respectively. In conclusion,^99mTc-L,l-EC clearance can be accurately estimated by simplified one or two-sample methods. Moreover, these methods can be used to estimate ERPF with an error that remains acceptable for clinical purposes.     

Estimation of technetium 99m mercaptoacetyltriglycine lasma clearance by use of one single plasma sample

Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gammacamera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m², was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18–14 ml/min), when the single plasma sample was taken 44–64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r = 0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF=1.86 × C_MAG-3 + 4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature. Offprint requests to: R. Müller-Suur     

Improved measurement of the glomerular filtration rate from Tc-99m DTPA scintigraphy in patients following nephrectomy

Objective

We aimed to improve Tc-99m DTPA glomerular filtration rate (GFR) scintigraphy (Gates’ method) in a prospective study using Cr-51 EDTA GFR test as a gold standard.

Methods

Fifty-seven Tc-99m DTPA GFR scintigrams in 45 subjects (male/female?=?33:12, age?=?45.9?±?17.6 years, 14 healthy volunteers and 31 nephrectomised patients) were compared using Cr-51 EDTA GFR tests. Using the %renal uptake of Tc-99m DTPA and Cr-51 EDTA GFR, a revised equation for GFR was established through linear regression analysis.

Results

The revised equation for improved GFR was GFR(mL/min)?=?(%renal uptake?×?11.7773)???0.7354. Gates’ original GFRs (70.1?±?20.5 mL/min/1.73 m²) were significantly lower than Cr-51 EDTA GFRs (97.0?±?31.9 mL/min/1.73 m²; P?<?0.0001), but the improved GFRs (98.0?±?26.3 mL/min/1.73 m²) were not different from (P?=?0.7360) and had a significant correlation with (r?=?0.73, P?<?0.0001) the Cr-51 EDTA GFRs. The revised GFR equation effectively demonstrated perioperative GFR changes in kidneys that were operated on and the contralateral kidneys at 3 and 6 months post-partial nephrectomy (n?=?25).

Conclusions

GFR measurement using Tc-99m DTPA scintigraphy could be significantly improved by a revised equation derived from the comparison with Cr-51 EDTA GFR.

Key Points

? Measurement of glomerular filtration rate is difficult following nephrectomy. ? Measurements can be significantly improved by new renal sctintigraphic methods. ? This helps physicians to measure kidney function of patients following nephrectomy. ? Management of renal tumour patients should become more effective.     

Reproducibility of technetium-99m mercaptoacetyltriglycine clearance

The aim of this paper was to determine the reproducibility (precision) of technetium-99m mercaptoacetyltriglycine (MAG3) clearance and to compare it with that of chromium-51 ethylenediamine tetra-acetic acid (EDTA). Twelve young volunteers (aged between 21 and 34 years), without any history of medical problems, were enrolled in this study. The test was performed twice, at an interval of 8 days and under similar physiological conditions. After the intravenous injection of both tracers, 15 blood samples were taken between 3 and 240 min. A biexponential fit was adapted to the plasma disappearance curves (5- to 120-min samples for^99mTc-MAG3 and 10- to 240-min samples for⁵¹Cr-EDTA); the clearances were calculated according to Sapirstein and corrected for body surface area. The mean clearance values were 110 (range 85–130) and 226 (range 109–319) ml/min/1.73 m², respectively, for⁵¹Cr-EDTA and^99mTc-MAG3. For⁵¹Cr-EDTA clearance, the mean difference between the first and the second measurement was –2.1% of the mean of the two successive values (SD: 8.4%). In ten cases, the difference was less than 12%; in two cases, the differences were 15% and 18%, respectively. For^99mTc-MAG3 clearance, the mean difference between the first and the second measurement was –20% of the mean of the two successive values (SD: 25%). In six cases, the difference was less than 12%; in four cases, between 15% and 40%; and in two cases, more than 60%. Methodological factors (impurites contained in the commercial kit, variable protein binding) as well as physiological factors (pH of urine, sodium load, stress) may explain the lack of precision of the^99mTc-MAG3 clearance. It is concluded that changes in^99mTc-MAG3 plasma clearance should be interpreted with care in daily routine.     

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.     

99mTc-DTPA gamma-camera renography: Normal values and rapid determination of single-kidney glomerular filtration rate

A method for ^99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, ^99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right-and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of ^99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of ^99mTc-DTPA. The coefficient of variation—a combination of inaccuracy and imprecision in the estimates as well as in the reference values — was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from ^99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium 99mTc pertechnetate (TcO4), 99mTc glucoheptonate ([99mTc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), 99mTc diethylenetriaminepentaacetate ([99mTc] DTPA), 111In diethylenetriaminepentaacetate ([111In]DTPA), 67Ga desferoxaminemesylate ([67Ga]DFOM), 99mTc dextran ([99mTc]DX) and 111In transferrin ([111In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [99mTc]GH (1.50 +/- 0.37%/min), [51Cr]EDTA (2.38 +/- 1.02%/min), [99mTc]DTPA (3.51 +/- 0.40%/min), [111In]DTPA (2.35 +/- 0.42%/min), [67Ga] DFOM (1.99 +/- 0.49%/min) and [99mTc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5,099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.     

Estimation of technetium-99m-MAG3 plasma clearance in adults from one or two blood samples

Technetium-99m mercaptoacetyltriglycine (MAG3) clearance is strongly correlated with effective renal plasma flow and can be used directly as a measure of renal function. For these reasons, formulas were developed for estimation of [99mTc]MAG3 clearance based on one or two plasma samples. A two-exponential model provided an excellent fit for 8-point plasma clearance curves obtained from 35 patients having a wide range of renal function. The 8-point [99mTc]MAG3 clearance could be estimated from a single point at 43 min with an error of 19 ml/min (residual s.d.) or from two samples at 12 and 94 min with an error of 7 ml/min. The relative errors with MAG3 are thus comparable to those reported for similar techniques used with [131I]orthoiodohippurate, [99mTc]diethylenetriaminepentraacetic acid and [51Cr]ethylenediaminetetraacetic acid.     

Prospective validation of a single sample technique to determine technetium-99m-MAG3 clearance.

Technetium-99m-MAG3 clearance is proportional to OIH clearance and can be used directly as a measure of renal function. Multiple plasma sample, two-compartment clearance data from three studies were recently pooled to develop a single-sample regression equation for determining the clearance of 99mTc-MAG3. To test this published equation, a prospective study was conducted in 34 patients with a wide range of renal function. Multiple plasma samples were obtained from 9 to 60 min following the bolus injection of 99mTc-MAG3 and the clearances were calculated based on a single injection, two-compartment model. Clearances were also calculated using a single 43-min plasma sample and the published regression equation. There was an excellent correlation (r = 0.976) between the two clearances; the slope of the regression line was 1.01 with an intercept of -26.6; the standard error of the estimate was 24 ml/min. In conclusion, the current regression equation provides a good estimate of 99mTc-MAG3 clearance.     

Quantitative Single-Photon Emission Computed Tomography/Computed Tomography for Glomerular Filtration Rate Measurement

Purpose

We propose a quantitative Tc-99m diethylenetriaminepentaacetic acid (DTPA) single-photon emission computed tomography/computed tomography (SPECT/CT) for glomerular filtration rate (GFR) measurement.

Methods

Quantitative SPECT/CT data obtained at 2–3 min post-Tc-99m DTPA injection (370 MBq) were used to determine % injected doses (%IDs) for individual kidneys. The reproducibility of %ID measurement was tested and compared with planar scintigraphy. Cr-51 ethylenediaminetetraacetic acid (EDTA) GFR was used as reference standard. Nine young volunteers, representing normal GFR, and ten older volunteers, reflecting impaired GFR, were enrolled. The established GFR equation derived from these volunteers was applied to 19 renal tumor patients post-partial nephrectomy.

Results

At 2?3 min, %ID was most reproducible with the highest intraclass correlation (ICC) (0.9379) and lowest % coefficient of variation (CV) (6.5259%), which were more reliable than the ICC (0.9368) and %CV (6.7689%) of planar scintigraphy. Cr-51 EDTA GFR (93.16 ± 24.81 ml/min) correlated significantly with %ID (7.66 ± 2.15%, r = 0.7906, p = 0.0001), yielding an equation: Cr-51 EDTA GFR (ml/min) = (%ID × 9.1462) + 23.0653. This equation revealed significant decreases in total and nephrectomized kidney GFR (p = 0.0012 and p < 0.0001, respectively) from preoperative to 3-month postoperative measurements.

Conclusions

Quantitative Tc-99m DTPA SPECT/CT produces reliable and clinically applicable %ID estimates that translate to the GFR of individual kidneys.

     

Estimation of technetium 99m mercaptoacetyltriglycine plasma clearance by use of one single plasma sample.

Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gamma-camera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m2, was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18-14 ml/min), when the single plasma sample was taken 44-64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r = 0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF = 1.86 x CMAG-3 + 4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature.     

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.     

Glomerular filtration rate in relation to extracellular fluid volume: Similarity between99mTc-DTPA and inulin

The rate constant ( ₂) of the terminal exponential of the technetium-99m diethylene triamine pentaacetic acid (DTPA) plasma clearance curve is close to the ratio of glomerular filtration rate (GFR) to extracellular fluid volume (ECV) and is therefore a convenient, already normalised, measure of filtration function. Since ₂ depends on the distribution volume of the tracer, our aim was to compare ₂ from inulin and^99mTc-DTPA and also to compare the equilibration kinetics of the two filtration markers. Fifty millititres of^99mTc-DTPA (250 MBq) and inulin (10%), mixed in the same syringe, were given by intravenous injection in 15 patients undergoing routine^99mTc-DTPA renography for a variety of clinical indications. Frequent antecubital venous blood samples were taken up to about 4 h after injection to construct plasma clearance curves from which GFR, ECV and GFR/ECV (i.e. the reciprocal of mean transit time through the distribution volume) were calculated.^99mTc-DTPA/inulin concentration ratio curves were also constructed after normalisation to the ratio in the syringe. GFR given by the two markers correlated closely (DTPA=0.98·inulin—0.4ml/min;r=0.98).^99mTc-DTPA had the same distribution volume as inulin, had a similar transit time through it and gave the same value of ₂ (r=0.98). GFR/ECV from^99mTc-DTPA accordingly correlated closely with GFR/ECV from inulin (DTPA=0.75·inulin+0.99 ml/min;r=0.95). Even though the distribution volumes and the times to equilibration (i.e. to reach the terminal exponential) were similar, the distribution volume of^99mTc-DTPA at about 10 min after injection was, after subtraction of the plasma volume, about twice that of inulin.We confirm the validity of^99mTc-DTPA for measuring GFR. ₂ is a convenient measure of GFR, can be based on the terminal exponential of inulin of^99mTc-DTPA curves and can be converted to GFR/ECV with an appropriate scaling factor. The kinetics or the two clearance curves with respect to anatomical correlates of the exponentials and the rates of diffusion throughout the respective distribution volumes requires further study.     

Measurement of glomerular filtration rate: single injection plasma clearance method without urine collection

Glomerular filtration rate (GFR) can be calculated from the plasma clearance of any of several radiopharmaceuticals that are excreted by glomerular filtration. Simplified methods have been proposed that require only one or two plasma samples in lieu of a more complete clearance curve. We examined the error introduced by this simplification. Forty patients were studied using a dual-isotope technique employing [99mTc]DTPA and [169Yb]DTPA, obtaining eight plasma samples for each clearance curve at intervals from 10 to 240 min after injection. Data were fit to several empirical or semiempirical formulae and also to a two-compartment computer model that permitted GFR estimation from only one or two data points. The computer model gave good fit, but so did several simpler methods. The error that results from replacing the complete clearance curve by a single 3-hr sample was about 8 ml/min (residual s.d.). By using two samples (at 1 and 3 hr), the error could be reduced to 4 ml/min. Recommended one- and two-sample methods are presented.     

Measurement of separate kidney clearance by means of 99mTc-DTPA complex and a scintillation camera

A new radioisotopic method of determining the separate glomerular clearance of the kidneys is described. After injection of ^99mTc-DTPA, the data from a scintillation camera are recorded by computer. The renal curves are corrected for extrarenal activity and the plasma curve is obtained from a precordial curve. At each instant the slope of the renal curve divided by the corresponding plasma concentration gives the separate clearance value, in the period extending from 80 to 180 s after injection of the tracer. The error and correction factors introduced are discussed. Normal values are established on 25 patients and correspond to inulin clearance values. Left kidney: 60 ml/min (SD=13). Right kidney: 57 ml/min (SD=12). The method is simple for the patient, takes only 20 min, is not dangerous, is particularly applicable to young children and can be repeated frequently in the same patient.