Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Extracellular fluid volume: A suitable indexation variable to assess impact of bariatric surgery on glomerular filtration rate in patients with chronic kidney disease.

BACKGROUND: Bariatric surgery (BS) might be a nephroprotective treatment in obese patients with chronic kidney disease (CKD), and the non-linear relation between body surface area (BSA) and extracellular fluid volume (ECFV) in obese people raises the question of the most relevant way to scale glomerular filtration rate (GFR) for assessing renal function changes after BS. METHODS: We screened 1774 BS candidates and analysed 10 consecutive participants with CKD stage 3. True GFR (mGFR), measured by the renal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA), was scaled either to BSA (mGFRBSA) or to ECFV measured by 51Cr-EDTA distribution volume (mGFRECFV) before and one year after BS. RESULTS: The 10 candidates for BS had a mean body mass index of 43.3 ± 3.6 kg/m2 and a mean GFR of 48 ± 8 mL/min/1.73 m2. Six participants had a sleeve gastrectomy and four had a Roux-en-Y gastric bypass. One year after BS, ECFV decreased (23.2 ± 6.2 to 17.9 ± 4.3 L, p = 0.001), absolute mGFR was not significantly modified (74 ± 23 versus 68 ±19 mL/min), mGFRBSA did not change significantly (53 ± 18 versus 56 ± 17 mL/min/1.73 m2) whereas mGFRECFV significantly increased (42 ± 13 versus 50 ± 14 mL/min/12.9 L, p = 0.037). The relation between mGFRECFV and mGFRBSA was different from the identity line before (p = 0.014) but not after BS (p = 0.09). CONCLUSION: There is a difference between mGFRBSA and mGFRECFV following BS and the latter might better reflect the adequacy between renal function and corpulence.

The added value of clinical radiopharmacists in nuclear medicine: The example of glomerular filtration rate assessment in kidney donors.

WHAT IS KNOWN AND OBJECTIVES: In Europe, the pharmaceutical supply of chromium-51 has been stopped. However, this isotope is necessary for the evaluation of glomerular filtration rates. It is possible to replace it with technetium-99m, but the validation of this change in the measurement method must be carried out. METHODS: A retrospective analysis of chromium-51 data from January 2018 to January 2019 was performed, followed by a study from January 2019 to January 2020 using the technetium tracer. The patients were different in the both study groups, and none had an eGFR below 50 mL min-1 . A cost analysis was performed. Patient exposure to ionizing radiation was studied for both methods. RESULTS AND DISCUSSION: Seventy-eight patients were included in the study. In total, 42 EDTA-51 Cr and 36 DTPA-99m Tc examinations were conducted and compared. There were no significant differences between the methods used to assess renal function (P = .351). The results of cost analysis and patient radiation exposure were in favour of DTPA-99m Tc examinations. WHAT IS NEW AND CONCLUSION: Within the limitations of a retrospective study of two patient cohorts, there was no significant difference between the results obtained with chromium-51 and technetium-99m tracers. In addition, with the use of DTPA-99m Tc, operating costs and patient exposure to ionizing radiation were reduced, and clinical activity was maintained for the patients' benefit. Radiopharmacists are able to react quickly to supply contingencies, reduce operating costs and maintain the quality of medical examinations.

Postoperative Renal Function in Patients Undergoing Unilateral Nephrectomy: Development of a Prediction Model Using Preoperative Risk Factors and 51Cr-EDTA Clearance.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the reference isotopic technique 51Cr-ethylene diamine tetra-acetic (51Cr-EDTA) and to create a model to predict the short-term postoperative GFR. Secondary aim was to evaluate which of the common equations for GFR estimation (Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) has the best correlation with the 51Cr-EDTA. Methods: Patients undergoing unilateral nephrectomy from 2014 to 2018 were selected. Pre- and postoperative variables were prospectively collected. Univariate and multivariate analyses were done to identify independent risk factors associated with renal function outcomes and to create a model to predict the postoperative GFR. Correlation analyses were performed to evaluate the performance of various serum creatinine-based equations for GFR estimation compared with 51Cr-EDTA. Results: In total, 107 patients were evaluated. After univariate and multivariate analyses, older age (p = 0.008), higher split function of the operated kidney on dimercaptosuccinic acid (DMSA) scintigraphy (p < 0.001), and lower preoperative 51Cr-EDTA (p < 0.001) were independent risk factors for higher GFR decline. Correlation analyses showed that GFR estimated by CKD-EPI equation had the best concordance to GFR measured by 51Cr-EDTA. Conclusions: Based on our findings age, DMSA and lower preoperative 51Cr-EDTA are predictors of postoperative renal function after unilateral nephrectomy. For the assessment of estimated GFR, CKD-EPI equation appears to have the best concordance with 51Cr-EDTA.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.

A prospective comparison of dynamic contrast-enhanced MRI and 51Cr-EDTA clearance for glomerular filtration rate measurement in 42 kidney transplant recipients.

OBJECTIVES: To evaluate the performance of dynamic contrast-enhanced MRI measurement of glomerular filtration rate (GFR) compared with the reference standard technique of urinary clearance of 51Cr-EDTA. PATIENTS AND METHODS: All kidney transplant recipients (KTRs) with an indication for non-urgent contrast-enhanced MRI at our institution were prospectively included between 2008 and 2012. Renographies were acquired by low-dose dynamic contrast-enhanced MRI (DCE-MRI) then fitted with a two-compartment pharmacokinetic model. MR-GFR was compared with reference isotopic measurements using Bland-Altman diagrams, intraclass correlation coefficient (ICC) and concordance rates. RESULTS: Forty-two KTRs (mean age 51.5 years, 26-74) were analyzed. Mean estimated GFR was 48.5 ± 27 mL/min/1.73m2 (24-178 mL/min). The mean bias was +13.2 mL/min (6.4-20.0, +36.9%) ranging from -31.0 mL/min (-41.7%) to +101.4 mL/min (+89.2%) with a large variability (standard-deviation: 22.3 mL/min; limits of agreement: [-30.6 (-43.3--18.9); +57.0 (45.3-68.7)]). The ICC was 0.32 (0.02-0.56) and the concordance rate was 28.6% (14.9-42.2). CONCLUSIONS: The large variability of MR-GFR compared with the reference technique precludes its use in KTRs, whose anatomical peculiarities make standardization of arterial input function (AIF) difficult.

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease.

BACKGROUND: In non-alcoholic fatty liver disease (NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis. We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD. AIM: To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet. METHODS: The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA). RESULTS: Twenty Caucasian patients, 90% male, median age 43 years, body mass index (BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight (-5.3 ± 4.1 kg, P = 0.003), mean waist circumference (-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase (ALT) -28.3 ± 11.9 IU/L, P = 0.0001; aspartate aminotransferase (AST) -6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet. CONCLUSION: Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.

Gut Barrier Dysfunction-A Primary Defect in Twins with Crohn's Disease Predominantly Caused by Genetic Predisposition.

Background and Aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function. Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to 51Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins. Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [p < 0.001] and without [p < 0.001] when compared with controls. A significant increase in 51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [p≤0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [p < 0.05] and affected twins [p < 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohn's disease twins [p < 0.05]. Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.

Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of 51 Cr-EDTA.

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of 51 Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 µmol l-1 entered the study. 51 Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg-1 body weight (150 mg ml-1 ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for 51 Cr-EDTA was 59·7 ± 18·8 ml min-1 . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min-1 and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min-1 , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min-1 . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and 51 Cr-EDTA for the assessment of GFR.

Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA.

There is a renewed interest from the pharmaceutical field to develop oral formulations of compounds, such as peptides, oligonucleotides, and polar drugs. However, these often suffer from insufficient absorption across the intestinal mucosal barrier. One approach to circumvent this problem is the use of absorption modifying excipient(s) (AME). This study determined the absorption enhancing effect of four AMEs (sodium dodecyl sulfate, caprate, chitosan, N-acetylcysteine) on five model compounds in a rat jejunal perfusion model. The aim was to correlate the model compound absorption to the blood-to-lumen clearance of the mucosal marker for barrier integrity, 51Cr-EDTA. Sodium dodecyl sulfate and chitosan increased the absorption of the low permeation compounds but had no effect on the high permeation compound, ketoprofen. Caprate and N-acetylcysteine did not affect the absorption of any of the model compounds. The increase in absorption of the model compounds was highly correlated to an increased blood-to-lumen clearance of 51Cr-EDTA, independent of the AME. Thus, 51Cr-EDTA could be used as a general, sensitive, and validated marker molecule for absorption enhancement when developing novel formulations.

Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention.

BACKGROUND AND AIM: In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. MATERIAL AND METHODS: A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. RESULTS: In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 mL/min/1.73 m(2). In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m(2), p < 0.0001). ClΔ increased with lower values of GFR (r = - 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. CONCLUSION: In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

Development of a modified sampling and calculation method for isotope plasma clearance assessment of the glomerular filtration rate in patients with cirrhosis and ascites.

AIM: The aim of this study was to identify a practical sampling regimen and calculation method that could be used to measure the glomerular filtration rate in patients with ascites using plasma sampling. PATIENTS AND METHODS: Thirteen potential liver transplant patients with cirrhosis and ascites were injected with Cr-51 ethylenediaminetetraacetic acid, and plasma samples were obtained at up to 16 time points for each patient. Reference clearance values were calculated using the area under the plasma clearance curve, which was calculated using all the available data points. Clearance calculations were then performed using three and four data points from each patient and three different calculation methods to identify a sampling regimen and calculation method that yielded good agreement with the reference values. RESULTS: The reference clearances ranged from 6 to 80 ml/min. Sampling at 2, 4, 8 and 24 h and calculation of the area under the plasma clearance curve using a log-linear trapezoidal rule with extrapolation to zero and infinity yielded a relative root mean square difference from the reference of less than 7%. CONCLUSION: This method for measuring glomerular filtration rate in patients with cirrhosis and ascites was found to be more accurate than the slope-intercept technique and is a practical alternative to urine collection.

Bioavailability of chromium(III)-supplements in rats and humans.

Chromium(III) is long regarded as essential trace element but the biochemical function and even basic transport ways in the body are still unclear. For a more rational discussion on beneficial as well as toxic effects of Cr(III), we re-investigated the bioavailability of the most important oral Cr supplements by using radiolabeled compounds and whole-body-counting in rats and in the first time also in humans. The apparent absorption of (51)Cr(III) from Cr-picolinate, Cr-nicotinate, Cr-phenylalaninate, Cr-proprionate, or Cr-chloride was generally low (0.04-0.24 %) in rats with slightly higher values for Cr-chloride and -phenylalaninate. Taking a fast urine excretion into account, the true absorption of (51)Cr was clearly higher for CrPic(3) (0.99 %), probably indicating a different uptake mechanism of this rather stable organic Cr complex. The bioavailability of CrPic(3) and Cr(D: -Phen)(3), the leading compounds in actual investigations, was analysed also in human volunteer by intraindividual comparison. The apparent absorption (=Cr bioavailability) of (51)Cr from both compounds was substantially higher in humans (0.8-1 %) than in rats. Again, most of freshly absorbed CrPic(3) was excreted into the urine resulting in the same low whole-body retention after 7 days for both compounds. In summary, the bioavailability of Cr from pharmaceutical Cr compound is lower than hitherto assumed. Importantly, humans absorb Cr(III) clearly better than rats. The absorption mechanism of CrPic(3) seems to be different from ionic Cr(III) but, as only the same low amount of Cr is retained from this compound, it is also not more bioavailable than other Cr compounds.

Comparison of 51chromium-labeled ethylenediamine tetra-acetic acid and iohexol as blood markers for intestinal permeability testing in Beagle dogs.

(51)Chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) is the gold standard probe for assessing intestinal permeability (IP) in dogs, but exposure to radioactivity is a disadvantage. Iohexol is a safe contrast medium commonly used for medical imaging purposes and has been successfully applied more recently for the assessment of IP in animal models and humans. This study aimed at comparing (51)Cr-EDTA and iohexol as IP blood markers in dogs. A test solution containing (51)Cr-EDTA and iohexol was administered intragastrically to seven healthy laboratory Beagle dogs, and percentage recoveries in serum were calculated. The strong linear association (correlation, r=0.76 and linear regression, y=0.03+5.04x) between (51)Cr-EDTA and iohexol supports the potential usefulness of iohexol as an IP blood marker in dogs.

Reliability of 5¹Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients.

PURPOSE: In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. METHODS: 5¹Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients' condition was generally stable, and all patients were investigated twice within 4-10 days. RESULTS: Plasma clearances of 5¹Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73 m², whereas urinary 5¹Cr-EDTA clearances ranged from 0.7-20.0 mL/min/1.73 m². This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. CONCLUSIONS: This study demonstrated a difference between 5¹Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of 5¹Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend 5¹Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of 5¹Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.

Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies.

Estimating GFR in children with 99mTc-DTPA renography: a comparison with single-sample 51Cr-EDTA clearance.

Glomerular filtration rate (GFR) measurement by (51)Cr-ethylenediaminetetraacetic acid (EDTA) and blood sampling in children is usually cumbersome for the patient, parents and laboratory technicians. We have previously developed a method accurately estimating GFR in adults. The aim of the present study was to evaluate the accuracy of this non-invasive method in children. We calculated GFR from (99m)Tc-diethylene triamine pentaacetic acid (DTPA) renography and compared with (51)Cr-EDTA plasma clearance of 29 children between the age of 1 month and 12 years (mean 4.7 years). The correlation between (99m)Tc-DTPA renography and (51)Cr-EDTA plasma clearance was for all children R = 0.96 (n = 29, P<0.0001), for children above 2 years of age R = 0.96 (n = 18, P<0.0001) and for children <2 years R = 0.84 (n = 11, P<0.001). We conclude that assessment of GFR from (99m)Tc-DTPA renography is reliable and comparable to GFR calculated from (51)Cr-EDTA plasma clearance. Because our method is non-invasive and only takes 21 min, it may be preferable in many cases where an assessment of renal function is needed in children especially when renography is performed anyhow.

Accurate measurement of extracellular fluid volume from the slope/intercept technique after bolus injection of a filtration marker.

Extracellular fluid volume (ECV) is studied infrequently. The zero-time distribution volume (Vd) generated in the slope-intercept technique for measuring the glomerular filtration rate (GFR) substantially overestimates ECV. The aim was to validate a new technique for measuring ECV from the slope-intercept approach. GFR and ECV were measured using Cr-51-EDTA and iohexol injected into opposite arms in 51 patients undergoing routine measurement of GFR and on 48 occasions in 20 healthy volunteers. Blood samples were obtained bilaterally 20, 40, 60, 120, 180 and 240 min post-injection and assayed for indicator injected contralaterally. Reference ECV (ECV6) was calculated from all six samples as the product of indicator transit time and multi-sample GFR. GFR/ECV was calculated as the rate constant of the exponential fitted to the last three samples (GFR/ECV3). Slope-intercept GFR was calculated from the last three samples using the slope-intercept technique (GFR3). ECV (ECV3) was calculated by dividing GFR3 by GFR/ECV3, having corrected both for their one-compartment assumptions. ECV6(EDTA) correlated closely with ECV3(EDTA) (ECV3(EDTA) = 1.01.ECV6(EDTA)-0.5 L; r = 0.97; n = 99), but less closely with Vd (Vd = 1.17.ECV6(EDTA) + 0.7 L; r = 0.86). ECV6(iohexol) correlated slightly better with ECV6 (EDTA) (ECV6(EDTA) = 0.81.ECV6(iohexol) + 3.3 L; r = 0.86) than with ECV3(EDTA) (ECV3(EDTA) = 0.83.ECV6(iohexol) + 2.9 L; r = 0.84) and had slightly narrower 95% limits of agreement (-3.82 and 2.82 L versus -3.90 to 3.43 L). In conclusion, ECV can be measured from three samples almost as accurately as ECV from multiple samples.

Absorption, excretion and retention of 51Cr from labelled Cr-(III)-picolinate in rats.

The bioavailability of chromium from Cr-picolinate (CrPic(3)) and Cr-chloride (CrCl(3)) was studied in rats using (51)Cr-labelled compounds and whole-body-counting. The intestinal absorption of Cr was twice as high from CrPic(3) (1.16% vs 0.55%) than from CrCl(3), however most of the absorbed (51)Cr from CrPic(3) was excreted into the urine within 24 h. After i.v. or i.p. injection, the whole-body retention curves fitted well to a multiexponential function, demonstrating that plasma chromium is in equilibrium with three pools. For CrPic(3), a large pool exists with a very rapid exchange (T (1/2) = <0.5 days), suggesting that CrPic(3) is absorbed as intact molecule, from which the main part is directly excreted by the kidney before degradation of the chromium complex in the liver can occur. CrCl(3) is less well absorbed but the rapid exchange pool is much smaller, resulting in even higher Cr concentrations in tissue such as muscle and fat. However, 1-3 days after application, the relative distribution of (51)Cr from both compounds was similar in all tissues studied, indicating that both compounds contribute to the same storage pool. In summary, the bioavailability of CrPic(3) in rats is not superior compared to CrCl(3).

[Monitoring renal function in patients treated with cytostatics]. / Måling af nyrefunktion under cytostatisk behandling.

INTRODUCTION: Some cytostatics, used in the treatment of cancer, are excreted by the kidneys and may be nephrotoxic. The glomerular filtration rate (GFR) represents a method for reliable assessement of the 51Cr-EDTA plasma clearance before and during treatment with nephrotoxic drugs. The aim of this retrospective study was to evaluate whether this method could be replaced by a more simplified GFR estimate calculated from the creatinine plasma concentration. MATERIALS AND METHODS: We included all patients who had had at least four GFR measurements in 2005 as part of their nephrotoxic cytostatic treatment. The estimated GFR (eGFR) was calculated from sex, age and weight, according to the Cockcroft formula. RESULTS: Forty-eight patients with a mean age of 47 years were included. 51Cr-EDTA plasma clearance and eGFR showed a poor correlation (r(2) = 0,678). On average, GFR decreased from 95 ml/min to 80 ml/min from the first to the fourth measurement, whereas plasma concentration of creatinine and eGFR remained unchanged. In 13 patients (27%), the treatment dose was reduced due to a fall in GFR. Seven of these 13 patients would have continued their treatment unchanged, if the clinical decision had been based on eGFR. CONCLUSION: Neither creatinine plasma concentration nor estimated GFR ad modum Cockcroft can be recommended for measurement of GFR in patients treated with nephrotoxic cytostatics.