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- Frennby, Bo, et al.
(author)
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Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques
- 1997
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:3, s. 241-252
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Journal article (peer-reviewed)abstract
- In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing "dose of marker" with "area under the plasma concentration curve" (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)-our reference method representing the "true" GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the median overestimation of the "true" GFR with Clprovisional was higher when "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the "true" GFR from 1.9 to 1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a "late" plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.
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- Frennby, Bo, et al.
(author)
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Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques
- 1996
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In: Academic Radiology. - 1878-4046. ; 3:8, s. 651-659
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker
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- Frennby, Bo, et al.
(author)
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Determination of the relative glomerular filtration rate of each kidney in man : Comparison between iohexol CT and 99mTc-DTPA scintigraphy
- 1995
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In: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 36:4, s. 410-417
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Journal article (peer-reviewed)abstract
- Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.
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- Frennby, Bo, et al.
(author)
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Extrarenal plasma clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and inulin in anephric pigs
- 1996
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In: Academic Radiology. - 1878-4046. ; 3:2, s. 145-153
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES: To improve the measurement of the glomerular filtration rate (GFR), we determined the extrarenal plasma clearance of the GFR markers iohexol, chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), and inulin using 11 anephric pigs. METHODS: After an intravenous (i.v.) bolus injection of the markers, the decay curves of their plasma concentrations were monitored for 29 hr by 16 plasma samples. The area under the curve (AUC; concentration of marker versus time) was calculated according to one- and three-compartment kinetics. The extrarenal clearance was calculated by dividing the dose of marker by the AUC. RESULTS: In the three-compartment model, the median of the extrarenal clearances of iohexol, 51Cr-EDTA, and inulin were 0.87 ml.min-1.10 kg-1 (range = 0.62-1.26 ml.min-1.10 kg-1), 0.79 ml.min-1.10 kg-1 (range = 0.61-1.04 ml.min-1.10 kg-1), and 0.83 ml.min-1.10 kg-1 (range = 0.65-1.17 ml.min-1.10 kg-1). The extrarenal clearance of 51Cr-EDTA was slightly lower than that of iohexol and inulin when measured with the three-compartment model (p = .015). There was no statistically significant difference between the two models of kinetics in calculating clearance of the same marker. CONCLUSION: Our results indicate that subtracting the median values of the extrarenal clearance of the markers from the total plasma clearance will provide GFR values closer to the "true" GFR. This technique might prove useful in GFR calculations in patients with a very low GFR (e.g., residual GFR in patients on dialysis)
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| 9. |
- Frennby, Bo, et al.
(author)
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Contrast media as markers of GFR
- 2002
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In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 12:2, s. 475-484
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Journal article (peer-reviewed)abstract
- Determination of the glomerular filtration rate (GFR) is generally considered as the most important parameter of quantifying renal function. The GFR is determined as renal or plasma clearance of an ideal filtration marker which is freely filtered by the kidney, does not undergo metabolism, tubular secretion or absorption. Markers that fulfil these demands are inulin, 51Cr-EDTA, 99mTc-DTPA, labelled or unlabelled contrast media. The renal clearance of inulin is the classic reference method for estimation of the GFR. This method is however not practical for routine clinical purposes. Radionucleids have therefore been used as alternative filtration markers since the 60s. Drawbacks related to radiation exposure especially in children and pregnant women and the safety in handling radiolabelled markers have led to an increasing interest in using non-radioactive markers. The development of simple and reliable methods to determine the concentration of contrast media in plasma and urine, such as high-performance liquid chromatography (HPLC) and X-ray fluorescence analysis have made this possible. The non-ionic low osmolar contrast medium iohexol has become the most commonly used contrast medium for GFR measurements in Europe. However, other contrast media with similar pharmacokinetics may be equally suitable as GFR markers.
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