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PubMedDate not supplied

Effect of region of interest selection and uptake measurement on glomerular filtration rate measured by 99mTc-DTPA scintigraphy in dogs.

Determinations of different methods of measurement of uptake of 99mTc-DTPA using scintigraphy of glomerular filtration rate (GFR) were made from 29 studies on 10 healthy beagle dogs. GFR was measured by calculating the percentage dose uptake (integral method) and rate of uptake (slope method) of 99mTc-DTPA using manual kidney regions of interest (ROI) and automatic kidney and background ROIs at different time periods of the uptake phase. These results were compared using linear regression analysis to the GFR obtained from 99mTc-DTPA plasma clearance using multiple blood samples. The best correlation coefficient between percentage DTPA uptake and GFR by DTPA clearance (r = 0.84, P < 0.001) was derived from time intervals between 30s-120s with a perirenal background ROI at 1 or 2 pixels out from the kidney ROI using automatic kidney ROI at 20% threshold. With the slope method, the best correlation coefficient (r = 0.85, P < 0.001) was obtained from time intervals between 30s-peak with the background ROI at 2 pixels out from the kidney ROI using automatic ROI at 35% threshold. The offset was higher, and the correlation varied more with different ROIs and the method was unreliable at time intervals extending beyond the peak radioactivity. Manual kidney ROIs with automatic background ROIs had slightly lower correlations. With DTPA renography both integral and slope uptake method with automatic kidney and background ROIs are accurate methods to estimate the GFR, but that the integral method is much more stable to variations in ROI size and the duration of the uptake phase of the renogram.

Animals↗
PubMed1999

Clearance kinetics of solutes used to measure glomerular filtration rate.

Agents used to measure glomerular filtration rate (GFR) give a biexponential plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are generally regarded to represent equilibration of agent throughout the extracellular fluid (ECF) space and renal clearance, respectively. In seven subjects undergoing diagnostic arteriography, arterial and antecubital venous plasma samples were obtained up to 60 min in five and up to 120 min in two following simultaneous intravenous injection of 99Tcm-diethylene triamine pentaacetate (99Tcm-DTPA) and inulin. The count rate from 99Tcm was simultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-concentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. Arterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V concentration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the interstitial space of the forearm, has a time course consistent with the second compartment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the composite of interstitial 99Tcm-DTPA and plasma 99Tcm-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the interstitial space of carcass tissue (mainly muscle and skin). The second exponential is minor compared with the first; it is not clear what it represents. The third exponential reflects renal clearance.

Adult↗
PubMed1995

Glomerular filtration rate measurement: a neglected test in urological practice.

OBJECTIVES: To assess the accuracy and reproducibility of methods used to measure glomerular filtration rate (GFR) in clinical practice. PATIENTS AND METHODS: Simultaneous clearances of iohexol, 99mTc-diethylene-triamine-penta-acetic acid (DTPA), 24 h renal creatinine clearance and creatinine clearance estimated from a serum sample only, were obtained in 31 patients. Accuracy was calculated relative to iohexol clearance. The reproducibility of each method was determined by repeat measurements in the same individuals: three 99mTc-DTPA clearances in 21 patients; three 24 h creatinine clearance estimations in 12 patients; and three serum creatinine clearance estimations in 21 patients. RESULTS: The mean differences between 99mTc-DTPA clearance, 24 h renal creatinine clearance and estimated creatinine clearance compared with the reference method were 0.2 mL/min, 21.6 mL/min and 0.6 mL/min, respectively. 99mTc-DTPA clearance had fairly tight 95% limits of agreement (12.2 mL/min) compared with 35.4 mL/min for 24 h creatinine clearance and 25.8 mL/min for estimated creatinine clearance. The reproducibility for each method was 5.4%, 24.3% and 6.1%, respectively. CONCLUSION: Single-injection 99mTc-DTPA clearance provides an accurate and reproducible method of GFR measurement that is suitable for objective monitoring of renal function. Twenty-four hour creatinine clearance is neither sufficiently accurate nor reproducible for this purpose. Creatinine clearance estimation from a serum sample without urine collection may be preferable to the more traditional 24 h collection method.

Creatinine↗
PubMed1995

A simple method for measuring glomerular filtration rate in dogs.

A technique for measuring glomerular filtration rate (by six-sample plasma clearance) and extracellular fluid volume is described. The results obtained for glomerular filtration rat per extracellular fluid volume with a three blood sample technique are also presented. Concurrently with the blood sample techniques measuring plasma clearance, glomerular filtration rate per extracellular fluid volume was also measured using an external radiation detector and no blood samples. The validity of expressing glomerular filtration rate per extracellular fluid volume (rather than per body weight or surface area) and the clinical utility of the results obtained with the external radiation detector are discussed.

Animals↗
PubMed1987

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.

Blood Volume↗
PubMed1991

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.

Body Surface Area↗
PubMed1996

Mosaic single plasma sample method for measuring glomerular filtration rate.

Seven single plasma sample methods for measuring glomerular filtration rate (GFR) were evaluated. When compared with GFRs calculated from a slope/intercept method proposed by Russell et al. [6] (using 1 h and 3 h plasma samples) as a reference standard, each single-sample method produced better results in different ranges of GFR (3 h plasma sample was used for all seven single-sample methods). Combining the best single-sample method in each range (mosaic) resulted in a regression line of y = 0.98x + 1.0, with a correlation coefficient of 0.980 and a standard error of estimate of 6.5 ml min-1 in 294 samples. This mosaic method yielded more accurate and realistic GFR values than any other individual single-sample method.

Adolescent↗
PubMed2003

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 patient's height and weight. An equation in common use was described by Haycock et al. and is BSA=0.024265 x weight(0.5378) x height(0.3964). An alternative indexation variable is ECFV. GFR per unit ECFV is close to the rate constant, alpha(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 alpha(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 alpha(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 alpha(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 x weight(0.6469) x height(0.7236). Indexation to ECFV abolishes differences that arise between children and adults when GFR is indexed to BSA.

Aging↗
PubMed2007

Glomerular filtration rate measurement and estimation in chronic kidney disease.

Glomerular filtration rate (GFR) assesses kidney function. GFR is measured by renal clearance techniques; inulin clearance is the gold standard but is not easily measured. Thus, other methods to determine GFR have been utilized. Endogenous creatinine clearance (CrCl) is the most widely used, but creatinine secretion falsely elevates GFR. Cimetidine inhibits creatinine secretion, such that CrCl equals GFR, provided there are no difficulties with bladder emptying. Estimation of GFR from serum creatinine (e.g. Schwartz formula) is useful clinically; however, such formulae have not been updated for enzymatic creatinine autoanalyzers. Cystatin C, a small protein, is produced at a relatively constant rate and is reabsorbed in the proximal tubule. Cystatin C may be more sensitive than creatinine in detecting a reduction in GFR, but further studies are needed to prove this. Single injection (plasma) clearance techniques are the most precise measures of GFR. Iohexol is an exogenous marker that is comparable to inulin and (51)Cr-EDTA and can be measured by high-performance liquid chromatography (HPLC). Our pilot and the Chronic Kidney Disease in Children (CKiD) North American studies show that iohexol can accurately measure GFR using a four-point plasma disappearance curve national studies show that iohexol can accurately measure GFR using a four-point plasma disappearance curve (10, 30, 120, and 300 min) or, in most cases, a two-point disappearance time (120 and 300 min).

Education, Medical, Continuing↗
PubMed1997

Long-term precision of glomerular filtration rate measurements using 51Cr-EDTA plasma clearance.

The long-term precision of chromium-51 ethylenediamine tetraacetic acid (51Cr-EDTA) measurements of glomerular filtration rate (GFR) was evaluated in a retrospective study of data obtained over a 12 year period. Each GFR measurement was derived from plasma samples taken at 2, 3 and 4 h following injection of 3 MBq 51Cr-EDTA. The records of 7507 patients were reviewed, from which 55 subjects were identified as having had studies on 10 or more occasions. The mean number of studies per patient was 12.9 (range 10-23) over a mean period of 9.4 years (range 4.3-11.8 years). Plots of GFR, clearance half-life, (T1/2) and volume of distribution (VD) were drawn for each patient and used to identify subjects showing linear changes with time that could be fitted using linear regression. Each residual was expressed as a percentage of the expected value calculated from the regression line and all the residuals combined to give histograms for GFR, T1/2 and VD. Each histogram was fitted with a normal distribution between the -3 S.D. and +3 S.D. limits using weighted least squares. Final results for the coefficient of variation were: GFR 9.8%, T1/2 6.7%, VD 9.4%. The precision errors were used to calculate the smallest statistically significant change measurable by the 51Cr-EDTA technique. With 10% significance and 80% power, the smallest measureable change was 30% for GFR and 20% for T1/2. Unless there are clinical grounds for thinking that a patient's volume of distribution has changed, T1/2 is the optimal parameter for identifying real changes in renal function.

Chromium Radioisotopes↗
PubMed2002

A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients.

BACKGROUND: The aim of this study was to compare measured glomerular filtration rate (GFR) with estimates of GFR derived from the population pharmacokinetic methods of Martin and Wright, and the creatinine clearance (CrCl) estimates of Cockcroft and Gault, and Jelliffe. PATIENTS AND METHODS: GFR was determined by technetium-99m diethyl triamine penta-acetic acid (Tc99DTPA) clearance in adult cancer patients. Height, actual body weight and serum creatinine were measured, and GFR and CrCl estimates calculated. RESULTS: One hundred and twenty-two patients were included. The mean measured GFR was 87 ml/min (range 30-174 ml/min). The mean bias (mean percentage error) was 2, 1, -10 and -17%, and the mean precision (mean absolute percentage error) was 18, 19, 21 and 23% for the Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively. The Martin formula significantly underestimates GFR for females (mean bias -10%) and overestimates GFR for males (mean bias 8%) (P <0.001 for bias of males versus females). The Wright and Martin formulas significantly overestimate GFR <50 ml/min (mean bias 39 and 30%; P = 0.03 and 0.05, respectively) and all formulas underestimate GFR >100 ml/min (mean bias -18, -16, -24 and -32% for Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively; P <0.001). CONCLUSIONS: All the assessed estimates for renal function were found to have significant limitations.

Adult↗
PubMed1990

[A comparison of three different techniques for measuring glomerular filtration rate].

The clearance of inulin, creatinine and radioactive tracers from the blood may be used to measure glomerular filtration rate (GFR). These techniques, however, are usually invasive and time-consuming. Although the clearance of a radioactive tracer is usually applied in nuclear medicine for the determination of GFR, it is also possible to convert the concentration of the tracer in the kidneys to absolute GFR by means of a regression equation. As this new technique is much faster, we have compared it with the conventional technique. A good correlation was found with the standard radionuclide techniques (r = 0.91), but the reference method was under-estimated on the average by 14 ml/min. The new regression equation derived in our clinic will ensure future accurate GFR measurements within 6 minutes.

Chromium Radioisotopes↗
PubMed1992

Comparison of three methods of glomerular filtration rate measurement with and without captopril pretreatment in groups of patients with left ventricular dysfunction.

Methods of glomerular filtration rate measurement by 51Cr EDTA elimination, inulin clearance and creatinine clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. Strong intermethod correlations were found in chronic heart failure patients (EDTA: inulin r = 0.87; EDTA: creatinine r = 0.84; inulin: creatinine r = 0.9; all P less than 0.00001). Despite this, substantial absolute differences were observed in results obtained by different techniques. In particular, creatinine clearance significantly overestimated both 51Cr EDTA (18.0 +/- 18.4 ml.min-1, mean difference +/- SD, P less than 0.001) and inulin clearance (26.8 +/- 17.0 ml.min-1, P less than 0.001). The slight reduction in 51Cr EDTA elimination on captopril versus placebo (-8.3 +/- 9.2 ml.min-1, P less than 0.05) was related to a similar treatment difference in inulin clearance (r = 0.67, p = 0.03), but changes observed by either method were unrelated to captopril-induced changes in creatinine clearance. Thus, creatinine clearance is an unsatisfactory means of assessing the effect of angiotensin converting enzyme inhibition on glomerular filtration rate in chronic heart failure. In the post-myocardial infarction group, correlations between methods were poorer (EDTA: inulin r = 0.79; EDTA: creatinine r = 0.76; inulin: creatinine r = 0.67). In this group no significant effect of captopril on glomerular filtration rate was detected by any technique. As compared to the chronic heart failure patients, the weaker relationship between techniques post-myocardial infarction may be related to interference by thrombolytic or aspirin treatment.

Captopril↗
PubMed1986

A comparison between four simple methods for measuring glomerular filtration rate using technetium-99m DTPA.

Numerous centers perform glomerular filtration rate (GFR) measurements on patients undergoing renal imaging with Tc-99m DTPA. GFR measurement, however, does involve multiple blood samples taken over a 4-hour period, and this has led to attempts to simplify the technique by reducing the number of blood samples required and hence diminish the time taken to perform the test and the inconvenience to the patient. Four different simplified techniques for measuring GFR that have been reported in the literature are compared with a reference 2 blood sample method. Three of the methods do not require any blood samples but have standard errors of greater than 20 ml/min in adults and greater than 14 ml/min in children. The other method requires one blood sample, and if this is taken at 2 hours postinjection, the standard error is 9 ml/min in adults and 5 ml/min in children. The latter method is suitable for routine use in renography when accuracy is not of paramount importance.

Adult↗
PubMed1997

Development of a nonisotopic capillary electrophoresis-based method for measuring glomerular filtration rate.

The conditions for quantitative measurement of nonisotopic iothalamate meglumine (Conray) in urine and plasma by capillary zone electrophoresis (CE) have been developed. The impetus for developing this methodology was to replace the traditional [125I]iothalamate glomerular filtration rate (GFR) marker assay, a routine tool in the measurement of kidney function. This new approach for measuring kidney function is attractive since it avoids the cost of administration of radioisotopic compounds to patients, as well as the cost associated with purchase and disposal of isotopic compounds and contaminated samples. The concentration of iothalamate in urine and plasma determined by CE can be used directly to calculate GFR. The GFR in patients injected with [125I]iothalamate and nonisotopic iothalamate simultaneously showed an excellent correlation (0.998) with between-day coefficient of variation of 2.30% and a recovery of 102% and 98%, respectively, when added to urine and plasma. Interference from drugs and other urinary compounds is eliminated with this method. Collectively, this study has shown that CE is a cost-effective alternative to the current methodology for measuring GFR.

Buffers↗
PubMed1992

Evaluation of a single injection of 99mTc-labeled diethylenetriaminepentaacetic acid for measuring glomerular filtration rate in horses.

Glomerular filtration rate (GFR) was measured in 12 clinically normal horses, using the standard inulin clearance method, and values were compared with values for 2 methods, using a single rapid IV injection of 99mTc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). The first 99mTc-DTPA method used a 2-compartment model to calculate GFR blood clearance of the tracer. The second method used sequential digital gamma camera images of the kidneys to determine fractional accumulation of the total dose of the tracer in the kidneys (percentage of injected dose, gamma camera) from 0 to 10 minutes after radionuclide administration. Linear correlation among the 3 methods was determined. Mean (+/- SD) GFR, using the inulin clearance method, was 154.67 +/- 42.28 ml/min/100 kg of body weight. Mean GFR, using the 2-compartment blood clearance curve, was 146.92 +/- 27.49 ml/min/100 kg. Mean GFR, using percentage of injected dose (gamma camera method) was 154.7 +/- 22.00 ml/min/100 kg. The percentage of injected dose (gamma camera method) did not correlate significantly to the inulin clearance results. However, a significant (r = 0.666, P less than 0.018) correlation was observed between the inulin method and the 99mTc-DTPA blood clearance method. Significant (P less than 0.0001) difference also was observed in the split function of the equine kidneys, with GFR of the right kidney contributing 60.1 +/- 9.12% of the total function, as determined by 99mTc-DTPA gamma camera imaging. Because the 99mTc-DTPA blood clearance method does not require urine collection, it may be a more practical procedure to measure GFR in the horse.

Animals↗