51Cr-EDTA Glomerular Filtration Rate Research Articles

COMPARISON STUDY OF CYSTATIN C & CREATININE-BASED GFR FORMULAS WITH 51CR-EDTA CLEARANCE IN PATIENTS WITH CIRRHOSIS

This study aimed to compare cystatin C and Creatinine based GFR equations with 51Cr-EDTA clearance as the gold standard in cirrhotic patients. A prospective study was conducted in the Hepatology & Medicine Departments of Tertiary Care Hospitals. A total of 140 patients were included in the study. 66 cirrhotic patients correlated with cystatin C with creatinine and 74 patients correlating 51Cr-EDTA glomerular filtration rate to adjustments of diet in renal disease and Larsson and Hoek formulas for Cystatin C were selected for the study. Bland-Altman plots and concordance correlation coefficients were used to evaluate agreements. The correlation between cystatin C and bilirubin was poor, and the correlation between bilirubin and creatinine was strong. The medium values of creatinine and cystatin C were greater in a group with a GFR of more than 70 ml (27 patients), and their difference was significant (p <0.0001). The new GFR obtained by the creatinine formula was more accurate than GFR obtained by the cystatin C formula. With a 50% change in GFR, the creatinine formula provided a 90% GFR estimate. CysC formulas are not better for estimating glomerular filtration rate than creatinine formulas.

Compartmental-modelling-based measurement of murine glomerular filtration rate using 18F-fluoride PET/CT

Accurate measurement of glomerular filtration rate (GFR) is essential for optimal decision making in many clinical settings of renal failure. We aimed to show that GFR can be accurately measured using compartmental tracer kinetic analysis of 18F-fluoride dynamic PET/CT. Twenty-three male Sprague-Dawley rats of three experimental groups (cyclosporine-administered [n = 8], unilaterally nephrectomized [n = 8], and control [n = 7]) underwent simultaneous 18F-fluoride dynamic PET/CT and reference 51Cr-EDTA GFR (GFRCrEDTA) test at day 0 and post-intervention day 3. 18F-fluoride PET GFR (GFRF-PET) was calculated by multiplying the influx rate and functional kidney volume in a single-tissue-compartmental kinetic model. Within-test repeatability and between-test agreement were evaluated by intraclass correlation coefficient (ICC) and Bland-Altman analysis. In the control group, repeatability of GFRF-PET was excellent (ICC = 0.9901, repeatability coefficient = 12.5%). GFRF-PET significantly decreased in the renally impaired rats in accordance with respective GFRCrEDTA changes. In the pooled population, GFRF-PET agreed well with GFRCrEDTA with minimal bias (−2.4%) and narrow 95% limits of agreement (−25.0% to 20.1%). These data suggest that the single-compartmental kinetic analysis of 18F-fluoride dynamic PET/CT is an accurate method for GFR measurement. Further studies in humans are warranted.

Radioisotopic Evaluation Glomerular Filtration Rate (GFR) before and after Kidney Donation

Background Because of the decrease of the nephron mass following nephrectomy, kidney donors (KD) develop a partial loss of renal function defined as Acute Kidney Injury (AKI) according to KDIGO criteria (Clinical Practice Guideline, 2012). The recovery of renal function following AKI is mainly ascribed to the concept of renal functional reserve (RFR), defined as the capacity of the kidney to increase glomerular filtration rate (GFR). However, only few studies correlated RFR in KD with long term functional outcomes. Aim of the Study The aim of the present study was to analyse 30 KD renal function before nephrectomy, in the immediate postoperative period and 1 year after the surgical procedure, developing the concept of estimated RFR (eRFR) for the long term follow-up of renal function in KD. Results KD mean age at the time of donation was 54.4 years (min-max, 30-78), mean serum creatinine 0.73 mg/dL (0.5-0.96), eGFR (CKD-EPI) 99 mL/min/1.73m2 (69-119) and radioisotope (51Cr-EDTA) GFR 101.4 mL/min (78-129). The split function was evaluated by concomitant scintigraphy using 99mTc-MAG: the mean percentage of renal function of right kidney was 48% (43-56) and left 52% (44-57), respectively. As expected, immediately after nephrectomy all KD worsened renal function: the mean percentage increase of serum creatinine was 79% (50-112.2%) within 72 hours post-surgery; most of KD (25/30) developed AKI stage 1, and 5 KD AKI stage 2 according to KDIGO criteria. Seven days after surgery, renal recovery was observed in all cases: the mean percentage increase of serum creatinine (50.6%) was significantly lower than the zenith of serum creatinine. These results suggest a potential gain of about 30% in comparison to the starting value of the right kidney. One year after nephrectomy (all KD were subjected to left nephrectomies), we studied KD renal function (GFR) by radioisotopic evaluation using 51Cr-EDTA and we then compared it with the split radioisotope (51Cr-EDTA) GFR of the right kidney at the first scintigraphic evaluation. Mean GFR was 68.8 mL/min (50-87) vs. 48.6 mL/min (39.7-60.4) before donation with an average GFR increase of 20 mL/min (0.8-45.6) and a percentage increase of the right renal function up to 110% (mean 42%, min 1.4%). Conclusions The results of this study show that radioisotopic evaluation is feasible and allows an estimated determination of RFR at different time points after nephrectomy in KD. We observed a compensatory hypertrophy due to RFR in all the 30 KD included in the study, independently from age and co-morbidities such as elevated BMI and hypertension. The limitation of this study is the evaluation of RFR only after the decrease of the nephron mass due to donation: we have now started a kidney stress test with a protein load to estimate RFR of KD before surgery with the aim of finding a correlation with radioisotpic GFR after nephrectomy.

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.

PurposeThe glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method.MethodsWe obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%.ResultsBetween August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated.ConclusionIn a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.

A new model for estimating glomerular filtration rate in patients with cancer.

e14074 Background: The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing, however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods: Data on age, sex, height, weight, serum creatinine, and results for GFR from 51Cr-EDTA excretion measurements (51Cr-EDTA GFR) were obtained from Caucasian patients aged 18 years or older with histologically confirmed cancer diagnoses at the University of Cambridge Hospital NHS Trust, UK. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared to the estimated GFR (eGFR) from seven published and our new model using an internal validation data set and root-mean-squared-error (RMSE) and median residuals. A comparison of carboplatin dosing accuracy based on an absolute percentage error more than 20% (APE > 20%) was undertaken. Results: Between August 2006 and January 2013 data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE 15.00ml/min (95% CI 14.12-16.00)) compared to all published models. Body surface area (BSA) adjusted CKD-EPI was the most accurate published models for eGFR (RMSE 16.30ml/min (95% CI 15.34-17.38)) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose APE > 20% to 14.17% in contrast to 18.62% for BSA adjusted CKD-EPI and 25.51% for the Cockcroft-Gault model. The results were externally validated. Conclusions: In a large data set, from patients with cancer, a new model improves eGFR and carboplatin dose calculations, when compared to BSA adjusted CKD-EPI, the model we identified as the best published model for determination of eGFR in patients with cancer.

A comparison of measured and estimated glomerular filtration rate (GFR) for carboplatin dose calculation in women with ovarian cancer (OC).

e17051 Background:Carboplatin based chemotherapy is widely used to treat women with Ovarian cancer (OC) in the adjuvant, neoadjuvant and palliative settings. Carboplatin is normally dosed by the Calvert formula: [GRF+25] x AUC, with a target AUC (area under the plasma concentration curve) of 5-6 mg/ml/min. GFR (glomerular filtration rate) can be precisely measured with radionuclide based ligands such as 51Cr-ethylenediamine tetraacetic acid (51Cr-EDTA), but in clinical practice is often estimated using formulae incorporating serum creatinine, weight and age, such as the Cockcroft–Gault (CG) or Wright (WR) formulae. It is unknown, however, if these formulae allow a sufficiently accurate dosing of carboplatin in OC patients. Methods:We retrospectively compared measured (EDTA-based) and estimated (CG and WR formulae) GFR and the resulting carboplatin doses, in women with stage 1c to IV OC treated with carboplatin AUC 6 at our centre between 2015 and 2016. All patients (pts) had concurrent 51Cr-EDTA GFR and serum creatinine measurement before starting carboplatin. Accuracy and bias of The WR and CG formulae were analysed using mean absolute percentage error (MAPE) and mean percentage error (MPE). Results:92 pts were included in the study (median age = 69 years (r. 25 -89), median serum creatinine 63.5 umol/L (r. 38 – 168)). MPE was -37.3 and -26.0 and MAPE was 38.0 and 32.2 for the WR and CG formulae, respectively. If the WR or CG formulae had been used instead of EDTA to calculate the dose of carboplatin, the discrepancy would have been at least 10% in 77.1% and 69.8% of pts, respectively; a discrepancy of 50% or more would have occurred in 10% and 13% of pts. Conclusions:Neither the WR nor CG formulae precisely predict renal function in ovarian cancer pts. They often overestimate GFR, meaning that if these formulae are used instead of isotope-based measurement of GFR, most pts will receive a higher dose of carboplatin. Our findings are relevant for clinical practice and for the design and interpretation of clinical trials, where the choice between EDTA- or formulae- based calculations of carboplatin dose are often left to investigators’ preference.

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer.

The updated bedside Schwartz equation requires constant, serum creatinine concentration and height measurements to calculate the estimated glomerular filtration rate (eGFR) in pediatric patients. Unlike the serum creatinine levels, obtaining height information from the laboratory information system (LIS) is not always possible in a clinical laboratory. Recently, the height-independent eGFR equation, the full age spectrum (FAS) equation, has been introduced. We evaluated the performance of height-independent eGFR equation in Korean children with cancer. A total of 250 children who underwent chromium-51-ethylenediamine tetra acetic-acid (51Cr-EDTA)-based glomerular filtration rate (GFR) measurements were enrolled. The 51Cr-EDTA GFR was used as the reference GFR. The bias (eGFR - measured GFR), precision (root mean square error [RMSE]) and accuracy (P30) of the FAS equations were compared to those of the updated Schwartz equation. P30 was defined as the percentage of patients whose eGFR was within ±30% of the measured GFR. The FAS equation showed significantly lower bias (mL/min/1.73 m2) than the updated Schwartz equation (4.2 vs. 8.7, p<0.001). The RMSE and P30 were: updated Schwartz of 43.8 and 64.4%, respectively, and FAS of 42.7 and 66.8%, respectively. The height-independent eGFR-FAS equation was less biased and as accurate as the updated Schwartz equation in Korean children. The use of the height-independent eGFR equation will allow for efficient reporting of eGFR through the LIS in clinical laboratories.

A comparison of measured and estimated glomerular filtration rate for carboplatin dose calculation in stage I testicular seminoma

Dose calculation of adjuvant carboplatin chemotherapy for stage I testicular seminoma, based on area under the concentration curve (AUC), incorporates the glomerular filtration rate (GFR). This retrospective study compares 'gold standard' (51)Cr-ethylenediamine tetraacetic acid ((51)Cr-EDTA) GFR measurements with renal function estimations derived from the Cockcroft-Gault, Jelliffe and Wright formulae. stage I testicular seminoma treated with a single dose of carboplatin AUC7 at one centre in South Wales, UK, between 2005 and 2011, with contemporaneous (51)Cr-EDTA GFR measurement and serum creatinine. Renal function estimates obtained using Cockcroft-Gault, Jelliffe and Wright formulae were analysed for bias (mean percentage error, MPE) and precision (mean absolute percentage error, MAPE) compared to the gold standard. Sixty-eight patients were identified, median age 40 (range 17-66), median creatinine 82 (range 55-120). For the Cockcroft-Gault, Jelliffe and Wright formulae, respectively, MPE was +12.4, -32.3 and +8.8; MAPE was 16.0, 32.7 and 12.9; and substitution of the calculated GFR result for (51)Cr-EDTA measurement would have resulted in a >10% discrepancy in carboplatin dose in 41.1, 97.1 and 42.6% of patients (predominantly overdoses for the Cockcroft-Gault and Wright formulae, underdoses for the Jelliffe formula). Of the formulae analysed, none accurately correlated with (51)Cr-EDTA GFR measurements.

1416 ARE WE EVALUATING PROPERLY THE RENAL FUNCTION WITH THE MODIFICATION OF DIET IN RENAL DISEASE (MDRD) IN PATIENTS WITH ORTHOTOPIC ILEAL NEOBLADDER?

You have accessJournal of UrologyUrinary Diversion: Bladder Reconstruction, Augmentation, Substitution, Diversion (II)1 Apr 20131416 ARE WE EVALUATING PROPERLY THE RENAL FUNCTION WITH THE MODIFICATION OF DIET IN RENAL DISEASE (MDRD) IN PATIENTS WITH ORTHOTOPIC ILEAL NEOBLADDER? Mathieu Rouanne, Yann Neuzillet, Dominique Eladari, Thierry Lebret, and Henry Botto Mathieu RouanneMathieu Rouanne Suresnes, France More articles by this author , Yann NeuzilletYann Neuzillet Suresnes, France More articles by this author , Dominique EladariDominique Eladari Paris, France More articles by this author , Thierry LebretThierry Lebret Suresnes, France More articles by this author , and Henry BottoHenry Botto Suresnes, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2770AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Few studies assessing prospectively the renal function changes after orthotopic ileal bladder substitution are available.The aim was to evaluate the accuracy of Modification of Diet in Renal Disease (MDRD) formulae as a substitute for the gold standard measure of glomerular filtration rate (GFR) using chromium 51 EDTA. METHODS Seventeen consecutive patients underwent radical cystectomy (RC) from July 2011 to December 2011 for muscle-invasive bladder cancer were included in this prospective protocol. Exclusion criteria were chronic kidney disease (CKD) and neoadjuvant chemotherapy. Bias and precision of estimated GFR (eGFR) were compared with isotopic GFR (iGFR). Chromium-51 ethylenediamine tetra-acetic acid (51 Cr-EDTA) was used to measure the glomerular filtration rate of both kidneys. 51Cr-EDTA GFR was performed preoperatively and 6 mo postoperatively. In addition, technetiumTc99m-diethylenetriaminepentaaceticacid (Tc99m-DTPA) renal scintigraphy was used to determine the glomerular filtration rate (GFR) of each kidney individually. RESULTS Mean preoperative GFR values were 84 ml/min per 1.73 m2 (range to 61-116) and 75 ml/min per 1.73 m2 (range to 60-117) using eGFR and 51 Cr-EDTA GFR respectively. At 6 mo, the mean GFR values were 77 ml/min per 1.73 m2 (range to 60-117) and 68 ml/min per 1.73 m2 (range to 60-102) using eGFR and iGFR respectively. At 6 mo, the difference between 51 Cr-EDTA GFR and eGFR was statistically different (p = 0.035). In addition, 51 Cr-EDTA GFR values were statistically different between preoperative time and at 6 mo ((p=0.025) whereas no statistical significant difference was found using eGFR (p > 0.05). CONCLUSIONS There is poor correlation between eGFR and 51Cr-EDTA GFR in patients with ileal neobladder reconstruction. eGFR should be used with caution as a surrogate marker for isotope GFR in these patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byRouanne M, Lebret T and Courbebaisse M (2018) Re: Long-Term Renal Function Outcomes after Radical CystectomyJournal of Urology, VOL. 193, NO. 3, (1066-1067), Online publication date: 1-Mar-2015. Volume 189Issue 4SApril 2013Page: e580 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mathieu Rouanne Suresnes, France More articles by this author Yann Neuzillet Suresnes, France More articles by this author Dominique Eladari Paris, France More articles by this author Thierry Lebret Suresnes, France More articles by this author Henry Botto Suresnes, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation Pronouncedly Underestimates Glomerular Filtration Rate in Type 2 Diabetes

OBJECTIVETo evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in type 2 diabetic patients with GFR >60 mL/min/1.73 m2.RESEARCH DESIGN AND METHODSThis was a cross-sectional study including 105 type 2 diabetic patients. GFR was measured by 51Cr-EDTA method and estimated by the MDRD and CKD-EPI equations. Serum creatinine was measured by the traceable Jaffe method. Bland-Altman plots were used. Bias, accuracy (P30), and precision were evaluated.RESULTSThe mean age of patients was 57 ± 8 years; 53 (50%) were men and 90 (86%) were white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria. 51Cr-EDTA GFR was 103 ± 23, CKD-EPI GFR was 83 ± 15, and MDRD-GFR was 78 ± 17 mL/min/1.73 m2 (P < 0.001). Accuracy (95% CI) was 67% (58–74) for CKD-EPI and 64% (56–75) for MDRD. Precision was 21 and 22, respectively.CONCLUSIONSThe CKD-EPI and MDRD equations pronouncedly underestimated GFR in type 2 diabetic patients.

Inaccuracies in estimated glomerular filtration rate in one Australian renal centre

Early identification of true renal disease (glomerular filtration rate (GFR) < 60 mL/min) results in better patient outcomes. There is now routine reporting in Australia of estimated GFR (eGFR) in all patients over age 18 who have serum creatinine measured, calculated by the Modification of Diet in Renal Disease (MDRD) formula, which was validated in an American Caucasian cohort. Significant clinical decisions and prognosis are often made on the basis of this calculation. To assess the accuracy of three estimates of GFR in an Australian population by comparing eGFR obtained by the abbreviated MDRD (aMDRD), Cockcroft-Gault corrected for body surface area (BSA) (CG) and Chronic Kidney Disease Epidemiology (CKD-Epi) formulae with a gold standard, isotopic (51) Cr-ethylenediaminetetra-acetic acid ((51) Cr-EDTA) GFR. Patients referred with an eGFR of <60 mL/min reported by the aMDRD formula underwent isotopic measurement of GFR (over 4 h) and had eGFR calculated using CG corrected for BSA, aMDRD and CKD-Epi formulae. Data were analysed using Bland-Altman plots and regression analysis to compare methods; bias, precision and the proportion of patients correctly stratified by stage of chronic kidney disease (CKD) were also compared according to the three estimates of GFR, using (51) Cr-EDTA GFR as the gold standard. A total of 139 patients were recruited (female 45%), mean age 64 years and mean serum creatinine 212 µmol/L. The mean GFR (SD) (mL/min per m(2) ) for isotopic, CG, aMDRD and CKD-Epi were 47 (28), 37 (20), 32 (17) and 33 (18) (P = 0.001). CG (57%) was more likely to correctly stage CKD than aMDRD (37%) or CKD-Epi (37%), and absolute bias was significantly lower using CG than either other method (P = 0.001). In this small Australian population the CG formula corrected for BSA agreed more closely with isotopic GFR and correctly staged patients with CKD more often than the aMDRD or CKD-Epi formulae. It is important that each renal Unit considers the accuracy of estimates of GFR according to their population demographics.

Correlation of estimated and measured glomerular filtration rate in patients with interposed bowel in the urinary tract

Isotope glomerular filtration rate (GFR) measurement is invasive, time-consuming and expensive. Estimated glomerular filtration rate (eGFR) is used as a surrogate, but has not been validated in patients whose lower urinary tract (LUT) is replaced with bowel. This study aimed to evaluate the correlation between the Modification of Diet of Renal Disease (MDRD) eGFR andchromium-51 ethylenediamine tetra-acetic acid (Cr-EDTA) GFR in patients with LUT reconstruction/diversion. A retrospective chart review was undertaken of 75 consecutive patients with LUT reconstruction/diversion attending scheduled follow-up in a single institutional setting. Cr-EDTA GFR, serum creatinine and eGFR were compared. Routine patient demographics, type of bowel reconstruction/diversionand time since surgery were noted. The correlation between Cr-EDTA GFR and creatinine was poor (r (2) = 0.411) and the limits of agreement between variables were wide (-118 to +102, p = 0.053). The correlation between Cr-EDTA GFR and eGFR was slightly better (r (2) = 0.536), and the limits of agreement narrowed to -39 to +37 (p = 0.0003). The correlation was improved (r (2) = 0.623) when separating patients with renal failure (eGFR ≤ 60 ml/min per 1.73 m(2), n = 21), but the agreement between variables was poor (-20 to +16 ml/min per 1.73 m(2), p = 0.424).Study limitations include the heterogeneous/complex patient population and types of bowel interposition, and asynchronous eGFR and Cr-EDTA GFR measurement (although no clinical events were recorded between measures). These reflect the reality in which eGFR is often used. There is poor correlation between eGFR and Cr-EDTA GFR in patients with LUT reconstruction/diversion with bowel. eGFR should be used with caution as a surrogate marker for isotope GFR in these patients. Larger prospective studies controlling for the study limitations identified are indicated.

51Cr-EDTA measurements of the glomerular filtration rate in patients with sickle cell anaemia and minor renal damage

Creatinine clearance has been reported to be inaccurate for the estimation of glomerular filtration rate (GFR) in patients with sickle cell anaemia (SCA). Inulin clearance, the reference method for GFR estimation, is impractical for routine use in these patients, and 51Cr-EDTA measurements of the GFR have been rarely reported in this disease. In order to obtain reference 51Cr-EDTA values in this disease, we studied 70 patients (40 females; 13-59 years of age, mean: 31.6 years) with homozygous SCA, normal serum creatinine and urinary albumin excretion < or =200 microg x min(-1). All patients were submitted to single-injection 51Cr-EDTA GFR, urinary albumin and haematocrit measurements. 51Cr-EDTA clearances were calculated in different age groups (<20, 20-29, 30-39, 40-49 and >50 years). The mean GFR (+/-standard deviation) obtained for the 70 patients was 111.5+/-23.1 ml x min(-1). Analysis of variance for evaluation of the possible interaction effect between 51Cr-EDTA clearance and sex, age, urinary albumin and haematocrit demonstrated patient age as the only factor influencing 51Cr-EDTA clearance (P < 0.001). The Spearman correlation coefficient showed a significant relationship between 51Cr-EDTA clearance and patient age (r = -0.44, P = 0.0001), but not between 51Cr-EDTA and urinary albumin (r = -0.17, P = 0.1546) or haematocrit (r = 0.079, P = 0.5121). The group aged 20-29 years presented the highest 51Cr-EDTA clearance mean value (126.7+/-20.4 ml x min(-1)), with a progressive reduction in the older groups. Young adults with homozygous SCA, normal serum creatinine and micro-albuminuria or normo-albuminuria present supranormal 51Cr-EDTA GFR values. These values rapidly decrease after 30 years of age. We did not find association between urinary albumin and GFR in these patients.

Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation

Renal dysfunction of variable severity is being increasingly recognized as a major complication of calcineurin inhibitors (CI), in some patients even necessitating renal transplantation. Close and effective monitoring of the renal function is indicated. Current methods for this monitoring are calculation of the glomerular filtration rate (GFR) based on creatinine or exogenous substances like 51Cr-EDTA. The first method is unreliable in children and the second is expensive and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular filtration but has not been evaluated in a large cohort of pediatric patients before and after liver transplantation (LT). We evaluated the accuracy of cystatin C in 62 children (30 male) with LT, who had their 51Cr-EDTA measured on 40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin C correlated better with 51Cr-EDTA GFR (r = .78) than the reciprocal of creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C predicting 51Cr-EDTA GFR < 80 ml/min/1.73 m2 was calculated. A level of 1.06 mg/L was found to have a sensitivity of 91% and a specificity of 81%. Applying this cutoff level in our patient group would have avoided 51Cr-EDTA GFR estimation in 43 of the 87 estimations. In conclusion, the use of this simple test could be recommended as screening of renal dysfunction in children with liver disease and after LT.

Reference data for 51Cr-EDTA measurements of the glomerular filtration rate derived from live kidney donors

51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) for the assessment of renal function. The aims of this study were to assess the dependence of GFR on age and gender and to produce reference data for the interpretation of 51Cr-EDTA GFR measurements in adults. This was a retrospective study of 428 subjects (218 females, 210 males; age range, 19-72 years) undergoing assessment as live kidney donors. GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h. The slope-intercept GFR was corrected for body surface area using the Haycock formula and for the fast exponential using the Brochner-Mortensen equation. The data were analysed for the dependence on age and gender using multivariate regression analysis. Precision was evaluated from duplicate measurements in 22 subjects. For 187 subjects, aged 19-40 years, the dependence of GFR on age was not statistically significant (P = 0.51). The mean GFR was 103.4 ml x min(-1) x (1.73 m2)(-1) with a root mean standard error (RMSE) of 15.5 ml x min(-1) x (1.73 m2)(-1). GFR was 1.3 ml x min(-1) x (1.73 m2)(-1) higher in men than in women, although the difference was not significant (P = 0.56). In 241 subjects, aged 40-73 years, GFR decreased by 0.91 ml x min(-1) x (1.73 m2)(-1) per year [standard error, 0.06 ml x min(-1) x (1.73 m2)(-1) per year] with an RMSE of 13.6 ml x min(-1) x (1.73 m2)(-1). Over both age groups GFR was 0.4 ml x min(-1) x (1.73 m2)(-1) higher in men than in women [P=0.80; 95% confidence interval, -2.4 to +3.1 ml x min(-1) x (1.73 m2)(-1)]. For the 22 subjects with duplicate measurements, the root mean square coefficient of variation was 10.4%. A model for the decline of GFR with age was produced in which GFR remains constant at 103.4 ml x min(-1) x (1.73 m2)(-1) until the age of 40 years and then declines at a rate of 9.1 ml x min(-1) x (1.73 m2)(-1) per decade. The data can be used to report the results of adult 51Cr-EDTA GFR investigations.

Susceptibility of glomerular filtration rate estimations to variations in creatinine methodology: a study in older patients

It is recommended that measurement of serum creatinine should be supplemented with a creatinine-based estimation of glomerular filtration rate (GFR). The influence of creatinine methodology on these estimates is not always appreciated. We have studied differences in creatinine methods and their influence on GFR estimation specifically in older people. In all, 46 older patients (mean age 80 y, range 69-92 y) with predominantly mild or moderate kidney disease were studied. Serum creatinine was measured using a rate Jaffe method and two different enzymatic methods. Isotope dilution mass spectrometry served as the reference creatinine method. GFR was estimated using both the Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault formulae: a 51Cr-EDTA GFR estimation served as the reference GFR method. Both enzymatic methods produced creatinine results that were significantly different (P<0.001) from the reference method. The Jaffe method over- and underestimated creatinine at low and high concentrations, respectively. The most likely explanation for these differences relates to standardization of the assays. Irrespective of creatinine method, the Cockroft and Gault formula tended to underestimate GFR, and the MDRD formula to overestimate GFR. Use of the differing creatinine methods to estimate GFR produced predictable biases of the estimate, with mean GFR estimates varying by 14% across the creatinine methods. Estimates of GFR depend critically upon the accuracy and precision of the creatinine measurement used in their calculation.

NEPHROTOXIC EFFECTS OF IMMUNOSUPPRESSANT THERAPY IN PAEDIATRIC LIVER TRANSPLANT RECIPIENTS.

P704 Introduction: Drugs used for immunosuppression have been implicated in numerous long-term side-effects including nephrotoxicity and cholesterol problems. Method: Review of 24 of our paediatric liver recipients performed at Red Cross Children’s Hospital, in terms of glomerular filtration rate and lipid profiles. Results: To date a total of 78 paediatric liver transplants have been performed (32 who are being followed up locally) and 24 of these were reviewed at least 5 months to a maximum of 7.3 years post transplant. Combined liver and kidney transplants were performed in 3 patients. 9 Boys and 15 girls were assessed with a racial distribution of 19 mixed race, 3 black and 2 white patients. Mean age of patients at time of transplant was 6.6 years (0.8 - 13.3 years) with 8 cases under the age of 3 years. Mean time post transplant was 2.1 years. All were commenced on Cyclosporin A therapy but at the time of testing, immunosuppression included 6 children on Cyclosporin and 18 children on Tacrolimus. Radionuclide 51Cr-EDTA Glomerular Filtration Rate (GFR) studies showed a range of 21 to 220ml/minute/1.73m2 (mean = 96.1, median = 89.9ml/min/1.73m2). 7 cases had a GFR of less than 75ml/min/1.73m2.21 of the children were on antihypertensives: 15 on 1 agent and 6 on 2 agents.Full fasting lipid profiles were done and total cholesterol ranged from 2 to7.9 (mean= 4.4). Only 1 case is currently on statin therapy. Conclusion: Immunosuppressive therapies such as the calcineurin inhibitors are known to cause nephrotoxicity and this is of concern in paediatric liver transplant recipients. Almost all our patients in the group studied currently require antihypertensive therapy. At present, the renal function is stable in the majority of the group but this study needs to be extended to include our other paediatric liver transplant recipients, with particular emphasis on those who are now more than 5 years post transplant.

Reference data for 51Cr-EDTA measurements of GFR derived from live kidney donors

Background: 51Cr-EDTA is widely used to measure glomerular filtration rate (GFR) for the assessment of renal function. Aim: To assess the dependence of GFR on age and gender and produce reference data for the interpretation of 51Cr-EDTA GFR measurements in adults. Methods: Retrospective study of 428 subjects (218 F, 210 M, aged 19 to 72 years) undergoing assessment as live kidney donors. GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h. The slope–intercept GFR was corrected for body surface area (Du Bois equation) and for the fast exponential (Brochner–Mortensen method). The data were analysed for the dependence on age and gender using multi-variant regression analysis. Precision was evaluated from duplicate measurements in 22 subjects. Results: For 187 subjects aged 19 to 40 years the dependence of GFR on age was not statistically significant (P=0.59). Mean GFR was 105.9 ml·min−1 with a root mean standard error (RMSE) of 16.4 ml·min−1. GFR was 2.4 ml·min−1 higher in women than men (P=0.35, not significant). In 241 subjects aged 40 to 73 years GFR decreased by 0.94 ml·min−1year−1 (standard error 0.07 ml·min−1year−1) in both sexes with an RMSE of 14.4 ml·min−1.Over the whole age range GFR was 2.8 ml·min−1 higher in women than men (P=0.06). For the 22 subjects with duplicate measurements the precision was 7.5 ml·min−1.

3. Impact of technique on 51Cr-EDTA glomerular filtration rate (GFR) results

3. Impact of technique on 51Cr-EDTA glomerular filtration rate (GFR) results

Number of Interstitial Capillary Cross-Sections Assessed by Monoclonal Antibodies: Relation to Interstitial Damage

Using thin Plexiglass sections stained with silver, the peritubular capillary area and number of capillary cross-sections can predict both interstitial damage and plasma creatinine concentrations. This technique is both difficult to perform and time-consuming. We have restudied this topic using conventional cryostat sections from 46 biopsies with chronic glomerulonephritis and tubulointerstitial nephritis and two monoclonal antibodies (MoAb) recognising capillary endothelium. Seven pretransplant biopsies acted as controls. The number of capillary cross-sections/mm2 was counted, and the degree of tubular atrophy, interstitial fibrosis and cell infiltration of the interstitium independently assessed on a semiquantitative scale using paraffin sections. These results were correlated with the plasma creatinine or 51Cr-EDTA glomerular filtration rate. Mean number of capillary cross-sections in normal interstitium was 373 +/- 50/mm2, and in the 46 biopsies studied 242 +/- 57/mm2. The number of capillary cross-sections reflected the plasma creatinine (r = 0.82, P less than or equal to 0.0001) and the glomerular filtration rate (r = 0.64, P less than or equal to 0.0001) at the time of biopsy with greater accuracy than any of the conventional gradings of interstitial damage on paraffin sections. We conclude that the use of anti-endothelial cell monoclonal antibodies makes counting capillary cross-sections easy and reliable, and that this technique can be employed to assess the extent of interstitial damage in conventional cryostat sections.