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Background: The aim was to evaluate the reproducibility of glomerular filtration rate (GFR) measured with iohexol and its response to food in a direct and independent comparison with Cr-51-ethylenediaminetetraacetic acid (EDTA), and examine the influence of two different whole body scaling parameters, body surface area (BSA) and extracellular fluid volume (ECV)., Methods: Fasting and non-fasting GFR were measured in 20 normal volunteers using Cr-51-EDTA and iohexol, simultaneously injected into opposite arms. In 10, the fasting study was repeated. Venous samples obtained bilaterally 20, 40, 60, 120, 180 and 240 min after injection were assayed for indicator injected contralaterally-Cr-51-EDTA by well-counting and iohexol by X-ray fluorescence. GFR scaled to BSA was measured from six samples (GFR/BSA6) and from the last three (GFR/BSA3). GFR scaled to ECV was calculated as the mean transit time of marker using six samples (GFR/ECV6) or the last three (GFR/ECV3)., Results: GFR/BSA3 was reproducible (coefficient of variations of 7.4% for Cr-51-EDTA and 7.6% for iohexol). Using Cr-51-EDTA, GFR/ECV3 (9.1%) and GFR/ECV6 (7.7%) were as reproducible as GFR/BSA3 and GFR/BSA6 (both 8.1%). However, GFR/ECV3 measured with iohexol had poorer reproducibility (16.8%). Food resulted in an increase in scaled GFR of about 5 ml/min but this was statistically significant only with respect to GFR/BSA (measured with Cr-51-EDTA or iohexol) and not GFR/ECV., Conclusions: Measured with Cr-51-EDTA, but not iohexol, GFR/ECV was as reproducible as GFR/BSA. GFR/BSA, measured with Cr-51-EDTA or iohexol, but not GFR/ECV, significantly increased after food.

Objective: The aim of the study was to assess a simplified method for measuring glomerular filtration rate (GFR) using iohexol that could form the basis of a decentralized service for measuring GFR by sample transportation., Material and Methods: Non-fasting GFR was measured with Cr-51-EDTA and iohexol injected simultaneously into opposite arms (n = 110). Cubital venous blood samples, obtained bilaterally 20, 40, 60, 120, 180 and 240 min after injection, were assayed for marker injected contralaterally, Cr-51-EDTA by well-counting and iohexol by X-ray fluorescence. Following biexponential analysis of the clearance curves, GFR was measured from all six samples and also from the last three samples and scaled to body surface area (BSA). GFR scaled to extracellular fluid volume (GFR/ECV) was calculated from six samples as the mean transit time of marker through its distribution volume and from three samples as the clearance half-time., Results: Cr-51-EDTA correlated closely with iohexol for measuring GFR/BSA (r = 0.97 for three samples, 0.94 for six). The two markers agreed more closely with each other in the measurement of GFR/BSA compared with GFR/ECV. GFR/BSA values showed better agreement with corresponding GFR/ECV values when they were measured with Cr-51-EDTA compared with iohexol. Six samples offered no significant advantage compared with three., Conclusions: Iohexol is less accurate than Cr-51-EDTA and scaling to BSA is more robust than scaling to ECV. Nevertheless, iohexol has potential to measure GFR by sample transportation, without having to measure injected dose. This would allow accurate measurement of GFR in a primary care setting.

Purpose: Exclusive use of the half-time of clearance of a filtration marker in the bolus injection, single compartment technique for measuring glomerular filtration rate (GFR) is a convenient approach that gives GFR (GFR(SO)) already scaled for extracellular fluid volume (ECV). It has been criticized as less accurate than the conventional, slope-intercept technique (GFR(SI)). The aim of the study was to compare the respective levels of agreement of GFR(SI) and GFR(SO) with GFR based on plasma creatinine (eGFR) used as an independent arbiter., Methods: GFR was measured with both 51Cr-EDTA and iohexol, simultaneously injected into opposite arms. Plasma obtained bilaterally 20, 40, 60, 120, 180 and 240 min after injection was assayed for marker injected contra-laterally, 51Cr-EDTA by well-counting and iohexol by X-ray fluorescence. ECV and GFR, scaled to body surface area (BSA), were formally measured from six samples and GFR(SI) (scaled to BSA) and GFR(SO) from the last three., Results: Disagreement between GFR(SO) measured with 51Cr-EDTA and eGFR was not significantly higher than the corresponding disagreement between eGFR and GFR(SI). Disagreement between GFR(SO) measured with iohexol and eGFR was significantly higher than between eGFR and GFR(SI). GFR(SI) and GFR(SO) correlated more closely when measured with 51Cr-EDTA than with iohexol. Individual differences between GFR(SI) and GFR(SO) using one marker correlated significantly with ECV measured with the other., Conclusions: GFR(SO) is critically dependent on the accuracy of half-time measurement and, measured with iohexol, appeared less reliable than GFR(SI). GFR(SI) and GFR(SO) measured with 51Cr-EDTA, however, have similar levels of reliability.

Extracellular fluid volume (ECV) is larger when measured with Tc-99m-DTPA ( approximately 500 Da) than inulin (6 kDa). As part of an assessment of the suitability of the non-radioactive marker, iohexol, against the gold standard tracer, Cr-51-EDTA, for measurement of the glomerular filtration rate (GFR) based on a postal service, we took the opportunity to determine if this volume dependence is present for diffusible markers less disparate in size than inulin and Tc-99m-DTPA. Cr-51-EDTA ( approximately 400 Da) and iohexol ( approximately 900 Da) were administered into the opposite arms of 20 normal volunteers (fasting and non-fasting) and 60 patients (non-fasting), including 36 diabetics, 10 cancer patients and 13 dermatology patients. Blood was obtained from both arms 20, 40, 60, 120, 180 and 240 min after injection and assayed for a marker injected contra-laterally. The glomerular filtration rate (GFR) and mean indicator transit time, T, were measured from the bi-exponential clearance curves. ECV, the product of GFR and T, was subdivided into V(1) (administered indicator divided by the sum of zero-time intercepts of the two exponentials) and V(2) (the difference between V(1) and ECV). Variables were scaled to 1.73 m(2). For all 100 studies, the mean GFR from Cr-51-EDTA was 3 ml min(-1) higher than iohexol (p < 0.01). ECV was 0.41 L higher (p < 0.02) and V(1) 0.65 L higher (p < 0.001) from Cr-51-EDTA but V(2) was 0.33 L lower (p < 0.02). V(1)/ECV was 0.031 higher from Cr-51-EDTA (p < 0.01). ECV and V(2) from Cr-51-EDTA were both higher in diabetics (15.1 [1.7] and 5.0 [0.095] L, respectively) compared with normal non-fasting subjects (13.7 [1.5] and 4.3 [1.0]; p < 0.01). ECV and the volumes of its sub-compartments are different between markers that are less than an order of magnitude different in size.

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

Unlabelled: 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.