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.     

The kinetic basis of glomerular filtration rate measurement and new concepts of indexation to body size

As measurement of glomerular filtration rate (GFR) is now generally the responsibility of departments of nuclear medicine, it is important for nuclear medicine physicians and scientists to understand the pharmacokinetics of the indicators and radiotracers that are used, generally known as filtration markers. The single-injection, non-steady state technique is almost universally used, departments varying in how many blood samples are taken: rarely multisample clearance, which does not assume a single compartment of tracer distribution, commonly clearance based on a limited number of blood samples between 2 and 4 h after injection, which assumes a single compartment of distribution, and often a single sample at a defined time point. The volume of distribution, V _d , of a filtration marker is close to extracellular fluid volume (ECFV). GFR and ECFV are both overestimated by the assumption of a single compartment by amounts that are functions of the rate of plasma clearance, Z. Residence time, T, of tracer in its V _d is equal to V _d divided by Z. Z and T can both be measured from a multisample clearance curve, whereupon V _d is the product of Z and T. GFR is usually indexed to patient size by expressing it in relation to body surface area (BSA), which in turn is calculated from an equation based on the patients height and weight. An equation in common use was described by Haycock et al. and is BSA=0.024265×weight^0.5378×height^0.3964. An alternative indexation variable is ECFV. GFR per unit ECFV is close to the rate constant, ₃, of the terminal exponential of the plasma clearance curve. It is in fact slightly higher than this rate constant by an amount that is a function of the rate constant itself. The discrepancy between GFR/ECFV and ₃ arises from the development of a concentration gradient between interstitial fluid and plasma, which in turn produces an extrarenal veno-arterial gradient throughout the body. Indexing GFR to ECFV not only has physiological attractions (especially in children) but is technically simple because it requires measurement only of ₃ (slope-only technique). A disadvantage, however, is a lack of robustness in comparison with the conventional slope/intercept method, which measures tracer dilution as well as ₃. Nevertheless, the advantages of indexation to ECFV can still be exploited by changing the constants of an equation of the Haycock type so that the equation becomes a predictor of ECFV rather than BSA. A recently described equation is ECFV=0.02154×weight^0.6469×height^0.7236. Indexation to ECFV abolishes differences that arise between children and adults when GFR is indexed to BSA.     

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.     

Normalisation of glomerular filtration rate measurements

The result of a glomerular filtration rate (GFR) measurement on a particular patient is of limited use to the referring physician since normal GFR values vary widely with the patient's age and build, etc. To overcome this problem, it is usual to normalise the measured GFR by dividing it by the patient's surface area and multiplying the result by the surface area of a standard man. This transforms the measurement onto a scale which applies to all patients, young and old, large and small, where normal values fall within a well-defined range and where the degree of renal impairment can be quantified. We have examined the generally accepted surface area (SA) and the less well-known extracellular volume (ECV) normalisation methods of GFR measurements in a series of 110 patients. The results show that both methods produce essentially the same result; however, ECV normalisation is theoretically more correct, can be found directly without the patient's ECV being measured and does not require the use of empirical formulae. Mathematical justification for ECV normalisation is presented, and a proposed distribution pattern for the normalised measurement is introduced. A simple mathematical model shows that accurate GFR measurements can be made in the presence of an enlarged ECV, but normalisation of these will produce misleading low values.     

The technetium-99m-DTPA renal uptake-plasma volume product: a quantitative estimation of glomerular filtration rate.

An image-based method for estimating quantitative renal glomerular filtration rates (GFR) by calculating the product of the renal uptake rate and plasma volume is presented. By using the relationship GFR = F.PV/t, F represents renal 99mTc-DTPA uptake after bolus injection, PV is the plasma volume and t is time. This GFR evaluation was carried out on 96 patients and compared to GFR values determined in the same patients using radiotracer blood clearance techniques relying on two venous blood samples. When estimating patient plasma volumes using patient's weight and measured hematocrit values, the image-based method for calculating GFR accurately approximates the values obtained from blood samples (linear regression slope = 1.03; y-intercept = -2.81 ml/min). The two techniques correlate with a value of r = 0.89.     

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.     

Effects of atrial natriuretic peptide on glomerular filtration rate in essential hypertension: a radionuclide study

A number of studies show that atrial natriuretic peptide (ANP) raises renal sodium excretion with a concomitant increase in glomerular filtration rate (GFR) in both experimental animals and normal humans. Studies using indirect evaluation of GFR have provided less consistent results in hypertensive patients. We studied the effects of intravenously administered (iv) -human ANP on GFR in patients with hypertension by a radionuclide technique using technetium 99m diethylenetriaminepenta-acetic acid. In six patients (ANP group), GFR was determined under control conditions, during iv ANP (initial bolus of 0.5 g/kg followed by a 21-min maintenance infusion at 0.05 g · kg^–1 · min^–1) and during a recovery phase. In six other patients (control group), GFR was determined under control conditions, during saline iv infusion and during recovery. The two groups did not differ with respect to age, sex, basal blood pressure, heart rate or GFR. In the ANP group, the infusion of the peptide induced a significant decrease of mean blood pressure (from 133 ± 5 to 120 ± 5 mmHg, P < 0.01), no change in heart rate and a significant increase in GFR (from 104 ± 4 to 125 ± 5 ml/min, P < 0.01). During recovery, blood pressure, heart rate and GFR were not different from the values recorded under control conditions. No changes in blood pressure, heart rate or GFR (from 106 ± 5 to 108 ± 5 ml/min, n.s.) were detected during saline infusion in the control group. Our results demonstrated that in patients with essential hypertension, ANP induces an augmentation in GFR in spite of a decrease in blood pressure; this suggests a unique role for atrial peptide-related drugs in the treatment of human hypertension.     

The ratio of right ventricular volume to left ventricular volume reflects the impact of pulmonary regurgitation independently of the method of pulmonary regurgitation quantification

Background

Previous studies have advocated quantifying pulmonary regurgitation (PR) by using PR volume (PRV) instead of commonly used PR fraction (PRF). However, physicians are not familiar with the use of PRV in clinical practice. The ratio of right ventricle (RV) volume to left ventricle volume (RV/LV) may better reflect the impact of PR on the heart than RV end-diastolic volume (RVEDV) alone. We aimed to compare the impact of PRV and PRF on RV size expressed as either the RV/LV ratio or RVEDV (mL/m²).

Methods

Consecutive patients with repaired tetralogy of Fallot were included (n = 53). PRV, PRF and ventricular volumes were measured with the use of cardiac magnetic resonance.

Results

RVEDV was more closely correlated with PRV when compared with PRF (r = 0.686, p < 0.0001, and r = 0.430, p = 0.0014, respectively). On the other hand, both PRV and PRF showed a good correlation with the RV/LV ratio (r = 0.691, p < 0.0001, and r = 0.685, p < 0.0001, respectively). Receiver operating characteristic analysis showed that both measures of PR had similar ability to predict severe RV dilatation when the RV/LV ratio-based criterion was used, namely the RV/LV ratio > 2.0 [area under the curve (AUC)_PRV = 0.770 vs AUC_PRF = 0.777, p = 0.86]. Conversely, with the use of the RVEDV-based criterion (>170 mL/m²), PRV proved to be superior over PRF (AUC_PRV = 0.770 vs AUC_PRF = 0.656, p = 0.0028].

Conclusions

PRV and PRF have similar significance as measures of PR when the RV/LV ratio is used instead of RVEDV. The RV/LV ratio is a universal marker of RV dilatation independent of the method of PR quantification applied (PRF vs PRV).     

Comparison between terminal slope rate constant and "slope/intercept" as measures of glomerular filtration rate using the single-compartment simplification

Several whole-body variables are available for indexing glomerular filtration rate (GFR), including extracellular fluid volume (ECF volume, ECV), which has the advantage that GFR based only on the terminal exponential, alpha 2, of the chromium-51 ethylene diamine tetraacetic acid (51Cr-EDTA) plasma clearance curve is a measure already indexed for ECV. This slope-only method, however, is open to the theoretical criticism of a lack of robustness not present in the more conventional slope/intercept method, which generates GFR in absolute units before indexation to body surface area (BSA). To further evaluate the slope-only method, a large database of routine three-sample GFR measurements, based on 51Cr-EDTA, was analysed with the aim of comparing GFR/BSA with GFR/ECV, identifying the main sources of error in their respective measurements and explaining why they might be discrepant. The database was subdivided into 304 patients (group A) in whom the correlation coefficient of the fit to the three data points was greater than 0.99 and 31 patients in whom it was less than 0.99 (noisy data; group B). There was modest agreement between GFR/BSA and GFR/ECV in group A (r = 0.77; mean ratio 1.01 +/- 0.21). The difference between them correlated significantly with BSA (r = 0.52; P < 0.001), as would be expected given that small individuals have a relatively high BSA. Subdividing group A into four subgroups stratified according to BSA led to a slight improvement in the correlation between GFR/BSA and GFR/ECV. Because an error in alpha 2 is balanced by an opposing error in the intercept (which leads to a change in distribution volume in the opposite direction), and therefore impacts on both GFR/BSA and GFR/ECV, whereas an error in administered dose affects only GFR/BSA, it is possible to evaluate such errors by examining the respective relationships of GFR/BSA and GFR/ECV with indexed ECV. In group A, GFR/BSA correlated positively with ECV/1.73 m2, not surprisingly as ECV/BSA is effectively the ratio GFR/BSA to GFR/ECV, while GFR/ECV correlated negatively with ECV/1.73 m2. This implies that errors other than alpha 2, probably principally in administered dose, were as important as errors in alpha 2. This conclusion was supported by disappearance of the positive correlation between GFR/BSA and ECV/BSA in group B, brought about by the greater errors in alpha 2 in this group. This study suggests that, because of the effects of errors in the slope/intercept method that do not affect alpha 2, GFR based on slope only is at least as robust as that based on slope/intercept.     

Indexing glomerular filtration rate to suit children.

In order to be able to compare individuals of differing size, glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA). This does not, however, suit children because they naturally have a relatively high BSA simply because of their small size. The aim of the study was to identify an appropriate simple whole-body variable based on height and weight suitable for indexing GFR that would be simultaneously appropriate for both children and adults. METHODS: A database of 532 routine clinical GFR measurements, each based on 3 venous blood samples obtained between 2 and 4 h after injection of (51)Cr-ethylenediaminetetraacetic acid, was analyzed to give GFR and, using only the half-time of the slope of the clearance curve, the quotient GFR to extracellular fluid volume (ECV). BSA was obtained from the Haycock formula, which is based on height and weight raised to indices to give units of area. Both GFR and GFR/ECV were corrected for the 1-compartment assumption using previously published empiric correction formulas. ECV was obtained by dividing GFR by GFR/ECV. An equation analogous to Haycock's was derived in which the indices of height and weight were varied to give an iterative best fit to ECV instead of BSA. RESULTS: GFR, ECV, and BSA increase as functions of age until about age 13 y, corresponding to a BSA of about 1.35 m(2), which was taken as the cutoff point between children and adults. As humans grow, their ratio of height to effective radius changes as a nonlinear function of surface area. Humans must therefore change shape as they grow. Moreover, the ECV-to-weight ratio decreases as a function of body size, suggesting that humans also change body composition as they grow. The new equation, giving an iterative best fit to ECV, was ECV = weight(0.6469) x height(0.7236) x 0.02154. ECV, either measured or estimated from the new equation, corresponding to a BSA of 1.73 m(2), was 12.9 L. Expressed as values normalized to the corresponding average adult values, the new equation and the second-order polynomial fit to ECV were superimposed as they increased as functions of BSA or weight. In contrast, normalized BSA and normalized weight were respectively larger and smaller than normalized ECV in children. GFR indexed to the new equation correlated more closely with GFR indexed to ECV than did GFR indexed to BSA and, along with GFR/ECV, showed a greater fall as a function of age than did GFR/BSA. CONCLUSION: When required in absolute units rather than as a rate of turnover of ECV, GFR is appropriately indexed to indices of height and weight as defined by this new equation, which avoids disadvantages to children from indexing to BSA. This unmasks higher values of filtration function in children than have hitherto been recognized.     

Determination of glomerular filtration rate by 111In-DTPA

To evaluate the use of ¹¹¹indium-diethylene-triamine pentaacetic acid (¹¹¹In-DTPA) for determination of the glomerular filtration rate (GFR), the results of 60 standard ¹¹¹In-DTPA clearances were compared with 24-h urine endogenic creatinine clearances obtained on 3 successive days (r=0.97, P<0.0001) and with endogenic creatinine clearances obtained during ¹¹¹In-DTPA determinations (r=0.93, P<0.0001). It is concluded that ¹¹¹In-DTPA is a useful marker for GFR     

Comparison of methods for determination of glomerular filtration rate: Tc-99m-DTPA renography, predicted creatinine clearance method and plasma sample method

Background: The gamma camera uptake method with Tc-99m-DTPA is simple and less time consuming for the determination of the glomerular filtration rate (GFR). However, its diagnostic accuracy is debated. Gates’ method and predicted creatinine clearance method were compared with plasma clearance method with Tc-99m-DTPA for the measurement of GFR.Materials and Methods: Tc-99m-DTPA renography was performed on 133 patients (69 males and 64 females; age range being 24 to 84 years) with a wide range of renal function. The GFR was determined simultaneously by 3 methods; (1) gamma camera uptake method (modified Gates, Gates); (2) predicted creatinine clearance method (Cockcroft-Gault, CG); (3) single- or two-plasma clearance method (plasma sample clearance method, PSC). The PSC was chosen as a reference.Results: The regression equation of the Gates and the CG against the PSC wasY=11.89 + 1.041X (r=0.790, p<0.001, RMSE=23.55 ml/min/1.73 m²) andY=8.845+0.7899X (r=0.8270, p<0.001, RMSE =16.27 ml/min/1.73 m²), respectively. In comparison with the GFR by PSC, the Gates tended to everestimate the GFR, and contrarily the CG tended to underestimate the GFR.Conclusion: The Gates correlates well with the PSC. However, the Gates is even less precise than the CG. The Gates’ method in Tc-99m-DTPA renography is not suitable for the estimation of GFR in routine practice.     

Determination of glomerular filtration rate (GFR) by analysis of capillary blood after single shot injection of 99mTc-DTPA

^99mTc-DTPA was prepared from a kit produced by the Institute of Atomic Energy, Oslo, Norway. Radiochemical purity as determined with gel chromatography ranged from 98.5–99.7% (n=7). The radiopharmaceutical showed no red cell uptake and not more than 0.2% protein binding in in vitro biokinetic studies.The clearance of ^99mTc-DTPA was compared to the clearance of ¹²⁵I-Iothalamate simultaneously using single shot intravenous injection and biexponential analysis of plasma activity disappearance rate according to Sapirstein et al. (1955). ¹²⁵I-Iothalamate was found to have a higher second volume of distribution than ^99mTc-DTPA, but there was no statistically significant difference in clearance.GFR calculated from capillary serum ^99mTc-DTPA count rates was in all subjects investigated virtually identical with GFR calculated from simultaneously collected venous plasma samples.Estimation of GFR on the basis of plasma activity curves obtained from sampling in two hours gave higher values than estimation from four hours sampling irrespective of kidney function and whether ^99mTc-DTPA or ¹²⁵I-Iothalamate was used.It is concluded that ^99mTc is almost entirely bound to DTPA after intravenous injection of the ^99mTc-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate, using both venous and capillary blood sampling.     

Comparison of glomerular filtration rate by Gates method with Cockroft Gault equation in unilateral small kidney

Objective

To compare the glomerular filtration rate (GFR) by ^99mTc DTPA scan and the Cockroft Gault method in unilateral small kidney.

Materials and methods

The present study was conducted in the Department of Nuclear Medicine at the Sher-i-Kashmir Institute of Medical Sciences (SKIMS), India from July 2007 to April 2011. The present study included 47 patients with a diagnosis of unilateral small kidney on ultrasound. Out of 47 patients, 21 (44.7%) were males and 26 (55.3%) were females. Image processing was done using camera based methods. The GFR was automatically calculated by a software in a commercially available computer according to the Gates algorithm. The predicted creatinine clearance was calculated according to the Cockroft and Gault equation.

Results

Mean total GFR by DTPA Gates method was 73.6 ± 18.6 ml/min and by the Cockroft Gault (CG) method was 79.8 ± 32.2 ml/min. The difference was statistically insignificant indicating an agreement between both the methods in measuring GFR.

Conclusions

To discuss the advantages of isotopic renography, CG cannot give individual kidney GFR and so is not of much use in the unilateral small kidney wherein the main aim is to know the function of the individual kidneys. Furthermore because of low cost and less radiation burden, this test might be preferred for routine practice in nuclear medicine.     

Normalisation of glomerular filtration rate measurements

The result of a glomerular filtration rate (GFR) measurement on a particular patient is of limited use to the referring physician since normal GFR values vary widely with the patient's age and build, etc. To overcome this problem, it is usual to normalise the measured GFR by dividing it by the patient's surface area and multiplying the result by the surface area of a 'standard' man. This transforms the measurement onto a scale which applies to all patients, young and old, large and small, where normal values fall within a well-defined range and where the degree of renal impairment can be quantified. We have examined the generally accepted surface area (SA) and the less well-known extracellular volume (ECV) normalisation methods of GFR measurements in a series of 110 patients. The results show that both methods produce essentially the same result; however, ECV normalisation is theoretically more correct, can be found directly without the patient's ECV being measured and does not require the use of empirical formulae. Mathematical justification for ECV normalisation is presented, and a proposed distribution pattern for the normalised measurement is introduced. A simple mathematical model shows that accurate GFR measurements can be made in the presence of an enlarged ECV, but normalisation of these will produce misleading low values.     

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.     

Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by⁵¹Cr-EDTA plasma clearance fell by 14% (P < 0.01), but renal uptake of^99mTc-DMSA increased by 10% (P < 0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR.     

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.     

Background in 99Tcm DTPA renography evaluated by the impact of its components on individual kidney glomerular filtration rate

Following injection for renography, 99Tcm-labelled diethylenetriamine-pentacetic acid (DTPA) rapidly enters the extravascular space. Background therefore comprises two components, a falling intravascular signal and an extravascular signal which initially rises. We estimated the relative magnitudes of these two components in terms of their impact on the calculation of differential renal function and individual kidney glomerular filtration rate (IKGFR) from the second phase of the 99Tcm-labelled DTPA renogram in 56 paediatric kidneys. We expressed each of the two background signals as a GFR equivalent. The GFR equivalent of the intravascular signal recorded from a peri-renal background region of interest (ROI), scaled by a factor equal to the ratio of the pixel numbers in the renal and background ROIs, was -39 (S.D. 14) ml min-1. The GFR equivalent of the extravascular signal was smaller than this and opposite to it at 23 (S.D. 10) ml min-1, giving a median ratio for the two equivalents of -1.68. Because of the opposing effects of the two background components on the second phase of the renogram, techniques recently described for the quantification of IKGFR from the renogram, and which eliminate the intravascular component, offer no theoretical advantage over a method of analysis which uses 'direct' subtraction of the total background signal. In practice, however, these new techniques are superior in their handling of 'noisy' data, consistently giving a lower coefficient of variation in their estimation of IKGFR.     

Three-hour volume of distribution method: an accurate simplified method of glomerular filtration rate measurement

Eight hundred studies of glomerular filtration rate (GFR) measurements were performed by the standard slope-intercept method using [99mTc]DTPA and results were compared with a simultaneous measurement of the 3-hr tracer volume of distribution. A wide range of human renal function was studied and a nonlinear relationship between GFR and the volume of distribution resulted with an excellent correlation (r = 0.989). Agreement between the two measured parameters was not constant for all levels of renal function with the greatest accuracy being found for GFR = 60 to 100 ml/min.