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ABSTRACT: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73 m, it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often 'that which is to be regulated' (i.e. ECV) comes into contact with the 'regulator' (i.e. the kidneys).
The aim of the present study was as follows: to analyse two published calculation methods for determining ECV and GFR/ECV; to develop a new simple and accurate formula for determining ECV; and to compare and evaluate these methods.
GFR was determined as Cr-EDTA clearance. The study comprised 128 individuals (35 women, 66 men and 27 children) with a full Cr-EDTA plasma concentration curve, determined from injection until 4-5 h p.i. Reference values for GFR and ECV were calculated from the full curve. One-pool approximations Cl 1 and V 1 were calculated using only the final-slope curve. Four calculation methods were compared: simple one-pool values; GFR/ECV according to Peters and colleagues; ECV according to Brøchner-Mortensen (BM); and ECV according to a new method (JBM): y=2x-1, where x=Cl 1/Cl and y=V 1/ECV.
The new JBM method is accurate and can be explained theoretically. BM has a slight bias for high renal function. The Peters method had bias in our data. GFR/ECV had better precision than ECV alone, especially for BM and JBM, which were within -4% to +7% of the reference values (95% limits of agreement in adults).
GFR/ECV can be precisely determined, especially with the BM and JBM methods. Expressing GFR/ECV in unit %/h gives a simple interpretation. Normal ranges for GFR/ECV need to be established.
Nuclear Medicine Communications 12/2012; 33(12):1243-53. · 1.40 Impact Factor
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ABSTRACT: BACKGROUND: The aim of this study was to compare the ability of renal indicators [serum creatinine (SCr), cystatin C (SCysC)] and glomerular filtration rate (GFR)-models to discriminate normal and reduced renal function. As a single cut-off level will always lead to false classifications, we propose using two cut-off levels, dividing renal function into normal or reduced, with an intermediate "gray zone" of indeterminable results. METHODS: Glomerular filtration rate was measured by plasma clearance of (51)Cr-EDTA (13.7-147.4 mL/min/1.73 m(2)) in 119 children (age range 2.3-14.9 years). Reduced renal function was defined as a GFR of <82 mL/min/1.73 m(2). SCr, SCysC, age-normalized creatinine (SCr-ratio), and eight published GFR-models were compared for their ability to correctly classify renal function as normal or reduced. Cut-off levels were determined so as to give 99 % certainty outside the gray zone. RESULTS: The multivariable GFR-models by Schwartz et al. (J Am Soc Nephrol 2009; 20:629-637) and Zappitelli et al. (Am J Kidney Dis 2006; 48:221-230) and two models by Andersen et al. [Am J Kidney Dis 2012; 59(1):50-57: body cell mass (BCM)-model and Weight-model] performed significantly better than all other variables (P < 0.01), with the BCM-model performing the best (P < 0.05). The SCr-based Schwartz formula and SCr-ratio both performed better than SCr and SCysC. CONCLUSIONS: Among the 119 children enrolled in this study and the renal indicators tested, the BCM-model had the best diagnostic performance in terms of screening for normal or reduced renal function, and the SCr-ratio was a superior diagnostic tool to both SCr and SCysC.
Pediatric Nephrology 09/2012; · 2.52 Impact Factor
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ABSTRACT: Aiming to develop a more accurate cystatin C-based model for estimation of glomerular filtration rate (GFR) in children, we hypothesized that inclusion of body cell mass (BCM) would increase the accuracy of the GFR estimate in comparison to a well-established GFR reference method.
Diagnostic test accuracy study.
119 children (mean age, 8.8; range, 2.3-14.9 years) referred for GFR measurement by chromium 51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance (mean GFR, 98; range, 13.7-147.4 mL/min/1.73 m(2)).
GFR estimations by the 2 prediction models resulting from theoretical considerations corroborated by forward stepwise variable selection: GFR (mL/min) = 0.542 × (BCM/SCysC)(0.40) × (height × BSA/SCr)(0.65) and GFR (mL/min) = 0.426 × (weight/SCysC)(0.39) × (height × BSA/SCr)(0.64), where SCysC is serum cystatin C level, BSA is body surface area, and SCr is serum creatinine level. The accuracy and precision of these models were compared with 7 previously published prediction models using random subsampling cross-validation. Local constants and coefficients were calculated for all models. Root mean square error, R(2), and percentage of predictions within ±10% and ±30% of the reference GFR were calculated for all models. Based on 1,000 runs of the cross-validation procedure, median values and 2.5th and 97.5th quantiles of the validation parameters were calculated.
GFR measurement by (51)Cr-EDTA clearance.
The BCM model predicted 98% within ±30% of reference GFR and 66% within ±10%, which was higher than for any other model. The weight model predicted 97.5% within ±30% of reference GFR and 62% within ±10%. The BCM model had the highest R(2) and the smallest root mean square error.
Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort.
The novel BCM model predicts GFR with higher accuracy than previously published models. The weight model is almost as accurate as the BCM model and allows for GFR estimation without knowledge of BCM. However, endogenous methods are still not sufficiently accurate to replace exogenous markers when GFR must be determined with high accuracy.
American Journal of Kidney Diseases 01/2012; 59(1):50-7. · 5.43 Impact Factor
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ABSTRACT: Bioimpedance spectroscopy (BIS) offers the possibility to perform rapid estimates of fluid distribution and body composition. Few studies, however, have addressed the precision and biological variation in a pediatric population. Our objectives were to evaluate precision, variation within- and between-days for the BIS-determined parameters total body fluid, extra-cellular fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular resistance, intra-cellular resistance and percentage body fat using a Xitron 4200.
All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one series measured on day one (precision population). Forty-four children had a second series on day one (within-day sub-population). Thirty-two children had a series measured on the next day (between-day sub-population). Each measurement series consisted of three repeated measurements. A linear mixed model was used for statistical analysis.
The precision was 0.3-0.8% in children ≥6 years and 0.5-2.4% in children <6 years with a statistically significant difference between the two age-groups (p<0.001). Within-day variation was 1.1-2.8% and between-day variation 2.4-5.7%. Total variation and reference change values are reported.
The Xitron 4200 has a very good but age-dependent precision. The median value of three repeated measurements is recommended in order to avoid incorrect measurements.
Clinical nutrition (Edinburgh, Scotland) 11/2010; 30(3):326-31. · 3.27 Impact Factor
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ABSTRACT: The one-pool or slope-intercept technique is widely used when determining total (51)Cr-EDTA plasma clearance (Cl). The one-pool clearance (Cl(1)), which always exceeds Cl, has mostly been corrected to Cl by multiplication by a constant factor = 0.80, suggested by Chantler (CH(0.80)), or by using a second-order polynomial originally proposed by Brøchner-Mortensen (BM) and later recommended by the British Nuclear Medicine Society (BM(BNMS)). Theoretical considerations indicate that the CH correction gives a systematic overestimate of Cl, whereas the BM correction may underestimate Cl at high values.
To assess the accuracy of Cl as estimated from Cl (1) corrected either by CH(0.80) or by second-order polynomials.
Cl(ref) was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma curve followed for 4-5 h after injection of (51)Cr-EDTA (range of Cl(ref) : 8-183 mL/min/1.73 m(2)). Cl(est) was determined from Cl(1) subsequently corrected by CH(0.80) and four second-order polynomials.
Using CH(0.80) correction, Cl(est) underestimated Cl(ref) (by a maximum of 20%) at Cl(ref) values less than about 100 mL/min/1.73 m(2) in children and 130 mL/min/1.73 m(2) in adults. At higher clearance levels, Cl(ref) was increasingly overestimated. Taking the BM(BNMS) correction as representative of second-order polynomials, Cl(est) increasingly underestimated Cl(ref) at high levels, the error being 10% at a Cl(ref) value of about 175 mL/min/1.73 m(2).
We suggest that the tested correction equations are replaced by the given common correction equation based on the "true" relationship between Cl(1) and Cl thoroughly described in part I of this study.
Scandinavian journal of clinical and laboratory investigation 03/2009; 69(3):314-22. · 1.38 Impact Factor
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ABSTRACT: Total plasma clearance of (51)Cr-EDTA, Cl, is widely used as a measure of GFR. Commonly, only the final part of the plasma concentration curve is measured, and a one-pool clearance (slope-intercept clearance), Cl(1), is computed. Empirically determined second-order polynomials of the general form Cl = b x Cl(1) + c x Cl(1)(2) are usually used to estimate Cl from a measured Cl(1). However, theoretical considerations indicate that such corrections underestimate Cl at high values.
To derive an analytically correct relationship between Cl and Cl(1) and determine the parameters involved for children and adults.
Cl was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma concentration curve followed for 4-5 h after injection of (51)Cr-EDTA (range of clearance: 8-183 mL/min/1.73 m(2)). Plasma volume, PV and the "missing" area under the plasma fraction curve, a (minutes), not used for determination of Cl(1), were measured.
The true relationship between Cl and Cl(1) is given by Cl = Cl(1)/(1 + f x Cl(1)), where f = a/PV. For men, women and children alike, the equation f = 0.0032 x BSA(-1.3) was applicable (BSA = body surface area in m(2)). Estimation errors on clearance were within +/-8% for adults and +/-13% for children (95% limits of agreement).
The true relationship between Cl and Cl(1) of (51)Cr-EDTA is given, resulting in a common correction equation applicable for children and adults. The new equation has better mathematical behaviour than quadratic equations on very high values of clearance and takes into account dependence on body size.
Scandinavian journal of clinical and laboratory investigation 01/2009; 69(3):305-13. · 1.38 Impact Factor
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Lars Jødal
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ABSTRACT: Beta emitters, such as (90)Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding.
To discuss practical precautions for handling beta emitters in general, and specifically determine proper shielding for (90)Y, while comparing to (177)Lu and (131)I. The aim is achieved through the application of physical principles combined with results from practical experience.
Typical and maximal electron ranges were calculated for (131)I, (177)Lu, and (90)Y, using data from a freely available database. Bremsstrahlung yields were calculated for (90)Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from (90)Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons preparing (90)Y-Zevalin were measured.
Good laboratory practice is important to keep radiation doses low. To reduce bremsstrahlung, (90)Y should not be shielded by lead but instead perspex (10 mm) or aluminium (5 mm). Bremsstrahlung radiation can be further reduced by adding a millimetre of lead on the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure.
Acta oncologica (Stockholm, Sweden) 10/2008; 48(2):308-13. · 2.27 Impact Factor
