Jens Brøchner-Mortensen

Selection of Routine Method for Determination of Glomerular Filtration Rate in Adult Patients

The precision and reporducibility of three different clearance methods as used in clinical routine assessment of glomerular filtration rate (GFR) were investigated in 51 patients: total [51Cr]EDTA plasma clearance (E); 24-hr endogenous creatinine clearance (C); and creatinine clearance estimated from the plasma creatinine concentration, weight, and sex- and age-dependent mean creatinine excretion rate (c). The precision and reporducibility (coefficient of variation) for single determinations were, in patients with E greater than 30 ml/min, 5.5 and 4.1% (E); 26.9% (C); and 23.2 and 11.0% (c). The corresponding figures for E less than 30 ml/min were 11.6 and 11.5% (E); 21.9% (C); and 21.4 and 6.5% (c). The precision of C could not be ameliorated by excluding single deviating determinations, but only by excluding patients for whom the precision of 15.5% for mean of three determinations of C (total material) could be reduced to 10% by excluding 25% of the patients. The present data indicate that E in most cases is the method of choice for assessment of GFR in clinical routine work. For changes in renal function, especially at low functional levels, c may be of value.

Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review

Our aim was to evaluate published methods that use serum cystatin C (s-CysC) for measuring glomerular filtration rate (GFR) in children and to discuss advantages and limitations of s-CysC and of established GFR methods. A comprehensive literature review of clinical studies in children evaluating s-CysC or CysC-based formulas and plasma creatinine or creatinine-based formulas against an exogenous reference method using receiver operating characteristics (ROC) curves or Bland–Altman plots is presented. The comparison of s-CysC with plasma creatinine indicated that s-CysC was superior to plasma creatinine in five of 13 studies; four studies showed no difference, and, in four studies, no statistical comparison was made. Comparison of s-CysC and the Schwartz formula showed that s-CysC was superior to the Schwartz formula in two of seven studies; two studies demonstrated no difference, and, in one study, the Schwartz formula was superior to s-CysC. In two studies no statistical comparison was made. The CysC-based prediction equations all had high accuracy but low agreement when compared with a reference GFR, in the range of 30–40% at best. S-CysC is most likely superior to plasma creatinine and at least equal to creatinine-based formulas. CysC-based prediction equations are at least as good as creatinine-based formulas but cannot replace exogenous methods.

Reliability of routine clearance methods for assessment of glomerular filtration rate in advanced renal insufficiency

The reliability of different clearance methods to assess the glomerular filtration rate (GFR) was tested in fifteen patients with advanced chronic renal failure (range of GFR: 3-13 ml/min). The renal [51Cr]EDTA plasma clearance (Er) measured during optimal conditions with determination of residual bladder-urine was used as reference parameter of GFR and the reliability (+/-) of a thus corrected value to assess GFR of the individual patient are given in parenthesis. The arithmetic mean of the renal plasma clearance of endogenous creatinine (Clcreat) and urea (2.0 ml/min; +/- 1.5 ml/min); single determination of 25-h clcreat (3.4 ml/min; +/- 2.0 ml/min); Clcreat calculated from a measured plasma creatinine concentration, considering sex, age and body weight of the patient (2.9 ml/min; +/- 2.3 ml/min); total [51Cr]EDTA plasma clearance (Et) determined form three blood samples drawn 3-5 h after i.v. single injection 93.7 ml/min; +/- 2.2 ml/min); and Et determined form two blood samples drawn 4 and 24 h after i.v. injection (0.5 ml/min; +/- 0.5 ml/min). It is concluded that the most reliable assessment of GFR (=Er) is achieved either form a direct measurement or indirectly from Et determined from two blood samples drawn 5 and 24 h after i.v. single injection. use of the mean value of three 25-h Clcreat determinations is recommended if facilities for measurement of radioactivity are not available.

Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance.

Background. Total plasma clearance of 51Cr‐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), Cl1, is computed. Empirically determined second‐order polynomials of the general form Cl = b⋅Cl1+c⋅Cl12 are usually used to estimate Cl from a measured Cl1. However, theoretical considerations indicate that such corrections underestimate Cl at high values. Aims. To derive an analytically correct relationship between Cl and Cl1 and determine the parameters involved for children and adults. Material and methods. 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 51Cr‐EDTA (range of clearance: 8–183 mL/min/1.73 m2). Plasma volume, PV and the “missing” area under the plasma fraction curve, a (minutes), not used for determination of Cl1, were measured. Results. The true relationship between Cl and Cl1 is given by Cl = Cl1/(1+f⋅Cl1), where f = a/PV. For men, women and children alike, the equation f = 0.0032⋅BSA−1.3 was applicable (BSA = body surface area in m2). Estimation errors on clearance were within ±8 % for adults and ±13 % for children (95 % limits of agreement). Conclusions. The true relationship between Cl and Cl1 of 51Cr‐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.

The influence of epidermal thickness on transcutaneous oxygen pressure measurements in normal persons

Transcutaneous oxygen pressure measurements (TcPO2) were performed in ten healthy men (age 30.6 years, range 28-35) in six regions: anterolaterally 10 cm below and above the knee on both legs, 5 cm laterally to umbilicus and on the inside of the left humerus, which was subsequently biopsied for measurements of epidermal thickness from the basal lamina to the uppermost layer of stratum granulosum. Transcutaneous oxygen pressure was on average 70 mmHg (range 42-88 mmHg), and that of epidermal thickness 70 microns (range 43-120 microns). Epidermis was thinnest on the inside of the humerus (mean +/- SD) 61.3 mu +/- 11.0 and about 25% thicker (NS) in the regions above and below the knees. The relationship between TcPO2 (y) and epidermal thickness (x) could be described by the regression equation y = alpha i - 0.26x where the intercept alpha i differed between subjects, the mean value being 88 mmHg (range 77-103). The common regression coefficient of -0.26 was significantly different from zero (p less than 0.01, r2 = 0.49). Although the oxygen gradient across the total epidermis can not be estimated from skin biopsies, correction for the thickness of the living part of the skin may prove beneficial when TcPO2 measurements are used as an indicator of wound healing. The results suggests that the change of oxygen tension across the living part of epidermis is 0.26 mmHg/micron at various skin locations in different subjects.

Tubular Reabsorption Rates as Related to Elevated Glomerular Filtration in Diabetic Children

To study renal tubular reabsorption and tubulo-glomerular balance in diabetic children, glomerular filtration rate (GFR) and tubular reabsorption rates of sodium, glucose, ultrafilterable calcium, and phosphate were measured during fasting in 26 ambulatory type I (insulin-dependent) diabetic children without clinical signs of microangiopathy (age 7–14 yr; duration of diabetes 3–14 yr). Similar measurements were made in 28 healthy school children (age 8–14 yr). Mean GFR in the diabetic children was significantly higher than in the normal children (138 versus 109 ml/min/1.73 m2, P < 0.01). Mean tubular reabsorption rates of sodium, glucose, and calcium were significantly increased in the diabetic subjects (P < 0.001). In contrast, tubular reabsorption rate of phosphate in the diabetic subjects was not enhanced. The renal threshold concentration of phosphate (TmPO4/GFR) was suppressed in the diabetic compared with the healthy subjects (1.23 versus 1.73 mmol/L, P < 0.001). TmP04/GFR was unrelated to circulating parathyroid and growth hormone concentrations but correlated inversely with the reabsorption rate of glucose (r = -0.53, P < 0.01). Sodium reabsorption was closely correlated to GFR in both diabetic (r = 0.99, P < 0.0001) and healthy subjects (r = 1.00, P < 0.0001), and both groups showed identical regression lines. The tubular glucose reabsorption rate was independent of GFR in the diabetics. Tubular calcium and phosphate reabsorptions correlated equally well with sodium reabsorption and with GFR in the diabetic and healthy subjects (P < 0.001). The maximal reabsorption of phosphate relative to GFR was lowered in the diabetic children. Thus, in the diabetic subjects, the tubulo-glomerular balance was maintained for sodium, but not for phosphate. These findings can be interpreted as a consequence of increased plasma (and ultrafilterate) glucose concentration inhibiting maximal phosphate reabsorption, leading to a stimulation of sodium coupled glucose reabsorption (cotransport), and thereby of solutelinked water reabsorption. The normalization of absolute phosphate reabsorption may be a consequence of the increased reabsorption of sodium. The excess sodium/solute-linked reabsorption is likely to be basic for the mechanism leading to the elevated GFR in the diabetic subjects.

Precision of single injection [51Cr]EDTA plasma clearance and endogenous creatinine clearance determinations in children

The precision of two different clearance methods as used for routine assessment of the glomerular filtration rate (GFR) was investigated in thirty-one children aged 0.6-14 years: total [51Cr]EDTA plasma clearance (E) determined by a simplified single injection method; and 24 h endogenous creatinine clearance (C). Determination of C twice only succeeded in twenty children because of problems in collecting 24 h urine accurately. The precision (determined from the total day-to-day variation) for single determinations in patients with E greater than or equal to 80 ml/min/1.73 m2 was 5.5% for E and 13.8% for C. The corresponding figures for E less than 80 ml/min/1.73 m2 was 7.8% for E and 20.8% for C. Data in the literature on the inaccuracies of C and E versus GFR suggest that the degree of inaccuracy in predicting GFR from C is much higher than that from E, a feature which together with the present findings on precision indicates that E is much more reliable than C for routine determination of GFR in children.

The extracellular fluid volume in normal man determined as the distribution volume of [51Cr] EDTA

The precision of a simplified single injection method for determination of the distribution volume of [51Cr] EDTA, as an estimate of the extracellular fluid volume (ECV), was determined in 49 patients (17 men and 32 women, aged 19-75 years) who had ECV determined twice with an interval of 1-5 days. The glomerular filtration rate (GFR) can be determined by the same method. The total day-to-day variation (coefficient of variation) of ECV was 11.4% and that of GFR 4.5%. ECV differed significantly between men and women so that ECV on average was 14% (P less than 0.001) and 7% (P less than 0.05) higher in men than in women for the same body weight and body surface area, respectively. Regression equations of ECV on body weight and body surface area in 44 normal men and in 40 normal women are presented.

Preoperative dual-phase parathyroid imaging with Tc-99m-sestamibi - Accuracy and reproducibility of the pinhole collimator with and without oblique images

Background: Previously, we have found that the additional use of a pinhole collimator in parathyroid scintigraphy resulted in a decrease in the number of incorrect side localizations and an increase in reproducibility compared with that of using a parallel-hole collimator alone. Purpose: The aim was to investigate whether the addition of anterior oblique views to parathyroid scintigraphy (PS) with a pinhole collimator could further enhance the diagnostic ability and reproducibility. The level of preoperative parathyroid hormone (PTH) as a potential predictor of the usefulness of the supplementary views was also studied. Method and Material: Forty-seven patients with primary hyperparathyroidism (HPT) underwent dual-phase PS using a combined protocol with parallel-hole and pinhole collimators. The pinhole collimator was used in the anterior as well as right and left anterior oblique positions. Thyroid pertechnetate scans were undertaken in the same positions. Two observers assessed the images independently. Results: By adding oblique views, the gain in correct side localization occurred in all cases but one was seen in patients with rapid washout. The level of PTH could not predict these patients. The observer agreement on correct side localizations rose significantly from 81% to 94%. Conclusion: The addition of oblique views to the imaging protocol using the pinhole collimator for parathyroid and thyroid scintigraphy in primary HPT results in an increase in observer agreement and the number of correct side localizations in patients with rapid washout of MIBI. The preoperative level of PTH cannot, however, predict these patients.

GFR Prediction From Cystatin C and Creatinine in Children: Effect of Including Body Cell Mass

BACKGROUND 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. STUDY DESIGN Diagnostic test accuracy study. SETTINGS & PARTICIPANTS 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)). INDEX TEST 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. REFERENCE TEST GFR measurement by (51)Cr-EDTA clearance. RESULTS 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. LIMITATIONS Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort. CONCLUSIONS 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.