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Background: Glomerular filtration rate (GFR) is commonly used to monitor chronic kidney disease (CKD) progression, but its validity for evaluating kidney function changes over time has not been comprehensively evaluated. We assessed the performance of creatinine-based equations for estimating GFR slope according to patient characteristics and specific CKD diagnosis., Methods: In the NephroTest cohort study, we measured GFR 5324 times by chromium 51-labeled ethylenediamine tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1-4 referred to nephrologists (Stages 1-2, 19%) and simultaneously estimated GFR with both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass spectrometry traceable creatinine; absolute and relative GFR slopes were calculated using a linear mixed model., Results: Over a median follow-up of 3.4 [interquartile range (IQR) 2.0-5.6] years, the decline in mean absolute and relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 ± 1.2, 1.5 ± 1.4 and 1.3 ± 1.3 mL/min/1.73 m2/year and 5.9 ± 5.3, 5.3 ± 5.3 and 4.8 ± 5.2%/year, respectively; 52% and 55% of the patients had MDRD and CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to overestimate the GFR slope in the youngest patients and underestimate it in the oldest, thus producing inverse associations between age and mGFR versus eGFR slope. Other patient characteristics and specific CKD diagnoses had little effect on the performance of the equations in estimating associations., Conclusions: This study shows little bias, but poor precision in GFR slope estimation for both MDRD and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due to variations in muscle mass over time, with implications for clinical care and research., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Drug dosing in patients with acute kidney injury (AKI) is based on the Cockroft-Gault (CG) equation-derived estimated Creatinine clearance (CGeCrCl) for historical reasons due to the lack of a validated method for estimating glomerular filtration rate (GFR) when Cr is rapidly changing. The kinetic equation (kinetic estimated GFR [KeGFR]) estimates GFR for the nonsteady-state Cr level. It is being validated in patient cohorts and could potentially be used for drug dosing when the Cr level is in the nonsteady state., Objective: The aim of the study was to measure the concordance and the degree of agreement between KeGFR-, CGeCrCl, and MDRD eGFR-based drug dosing categories in patients with nonsteady Cr levels., Methods: In the pilot study published previously, 80 adult patients with a significant change in Cr level after admission to the acute medical ward were classified as per the Acute Kidney Injury Network (AKIN) criteria and compared to a KeGFR-based criterion. The CG equation and the MDRD equation were applied retrospectively to the same dataset, and the concordance of the eGFR categories between the 3 methods was studied. The 3 eGFR categories (<30, 30-49, and >50 mL/min) were chosen to reflect the frequently used drug dosing categories in patients with renal impairment., Results: The concordance between CGeCRCL and KeGFR for drug dosing categories was only 62%, with 27 (90%) of the 30 discordant subjects falling into a higher eGFR category when KeGFR was used. The agreement between KeGFR and CGeCrCl was also unsatisfactory. There was better concordance (75%), but the agreement was also not satisfactory between MDRD eGFR and KeGFR for the drug dosing categories., Conclusions: In AKI, compared to CGeCrCL, using KeGFR may affect drug dosing significantly by changing the eGFR category. Further studies of KeGFR for drug dosing will need therapeutic drug monitoring and pharmacokinetic studies for validation., (© 2020 S. Karger AG, Basel.)

Background: When estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques., Objective: To analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51 Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year., Results: The mean measured GFR was 43.0±11.4 (18.2-79.4)ml/min/1.73m 2 , with creatinine levels of 1.42±0.46 (0.60-4.33)mg/dl and cystatin C levels of 1.45±0.53 (0.42-3.48)mg/l. This correlated moderately with creatinine (r=-0.61, P<.001) and cystatin C (r=-0.52, P<.001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1ml/min/1.73m 2 for MDRD, +16.4ml/min/1.73m 2 for 2009-CKD-EPI, +15ml/min/1.73m 2 for CKD-EPI with cystatin C, and +14.1ml/min/1.73m 2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51 Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60ml/min/1.73m 2 ., Conclusions: The 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equations is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations., (Copyright © 2019 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: This study validates two popular predictive equations of renal function firstly, Modifications of Diet in Renal Disease and secondly, Chronic Kidney Disease Epidemiology Collaboration equations for Sri Lankan cohort. We used data of the patients referred to Renal Research lab of University of Colombo for creatinine clearance measurement., Results: Predictive performances varied with the gender. Creatinine clearance and predicted renal functions were compared. Both fared unsatisfactorily with R 2 ranging from 0.632 to 0.652, and overestimated renal function by 6-15%. The proportion chronic kidney disease staging 1 and 2 returned by Chronic Kidney Disease Epidemiology Collaboration equation showed significant difference, in females. Modifications of Diet in Renal Disease equation significantly under-estimated advanced chronic kidney disease in females. Chronic Kidney Disease Epidemiology Collaboration equation had better accuracy. The study sample had more females, Asian and lower body size and better renal functions than historic cohorts. Thai and Pakistani studies show both equations and their Asian adaptations fare poorly. Chronic kidney disease stages differ significantly with the equation used. Predictive equations have fared unsatisfactorily by overestimating renal functions. We recommend further studies using gold standards of measuring renal function.

Background: The estimation of glomerular filtration rate (GFR) plays a vital role in assessment of the renal function. This study evaluated the performance of the CKD-EPI creat and MDRD equations in the South African Kwa-Zulu Natal population., Objectives: The objectives if the study were to compare the of CKD-EPI creat and MDRD equations in the selected population to the measured GFR using Sodium Technetium-99 m-diethylene-triamine-pentaacetate clearance derived GFR., Method: Records of adult patients with measured GFR performed at the Nuclear Medicine Department at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 1 April 2014 to 31 March 2016 were reviewed. eGFR for all included patients was calculated using the MDRD equation without African American correction factor and the CKD-EPI creat equation with and without the African American correction factor for the Black African patients. Statistical comparison of the eGFR with measured GFR was performed with Bland Altman bias plots, Wilcoxon match pairs signed ranks test and accuracy within 10% and 30%.ROC curve analysis assessed the sensitivity and specificity at eGFR <90 and < 60 ml/min/1.73m 2 ., Results: After exclusion, 287 patients were included for analysis with sufficient numbers for only the Black African and Indian patients. None of the equations showed accuracy of eGFR within 30% of measured GFR for 90% of patients. In the Black African population, the CKD-EPI creat equation without the correction factor performed best. 17% and 14.4% of the Black African participants would be reclassified with the CKD-EPI creat equation without and with the African American correction factor respectively compared to mGFR at a cut-off of 60 mls/min/1.73m 2 ., Conclusion: None of the evaluated equations attained the 2002 KDOQI benchmark of P 30 >90%. 11.1-17% of individuals would have been incorrectly classified using the CKD-EPI creat equation., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is diagnosed using the estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (ACR). The eGFR is calculated from serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations., Aim: To compare the performance of one versus two eGFR/ACR measurements, and the impact of equation choice, on CKD diagnosis and classification., Design and Setting: Cohort study in primary care in the Thames Valley region of the UK., Method: Data were from 485 participants aged >60 years in the Oxford Renal Cohort Study with at least two eGFR tests. The proportion of study participants diagnosed and classified into different CKD stages using one and two positive tests were compared. Prevalence of CKD diagnosis and classification by CKD stage were compared when eGFR was calculated using MDRD and CKD-EPI equations., Results: Participants included in the analysis had a mean age of 72.1 (±6.8) years and 57.0% were female. Use of a single screening test overestimated the proportion of people with CKD by around 25% no matter which equation was used, compared with the use of two tests. The mean eGFR was 1.4 ml/min/1.73 m 2 (95% CI = 1.1 to 1.6) higher using the CKD-EPI equation compared with the MDRD equation. More patients were diagnosed with CKD when using the MDRD equation, compared with the CKD-EPI equation, once (64% versus 63%, respectively) and twice (39% versus 38%, respectively), and 16 individuals, all of who had CKD stages 2 or 3A with MDRD, were reclassified as having a normal urinary ACR when using the CKD-EPI equation., Conclusion: Current guidance to use two eGFR measures to diagnose CKD remains appropriate in an older primary care population to avoid overdiagnosis. A change from MDRD to CKD-EPI equation could result in one in 12 patients with a CKD diagnosis with MDRD no longer having a diagnosis of CKD., (© British Journal of General Practice 2018.)

Background: Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC)., Methods: This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA ( 51 Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (Cr Jaffe ). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined., Results: A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m 2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m 2 , while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p < 0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%)., Conclusion: The CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

Background: Renal function impairment is common in geriatric palliative care patients. Accurate assessment of renal function is necessary for appropriate drug dosage. Several equations are used to estimate kidney function., Aims: 1) To investigate the differences (Δ) in kidney function assessed with simplified Modifi-cation of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS1), and Cockcroft-Gault (C-G) formulas in geriatric palliative care patients, and 2) to assess factors that may influence these differences., Methods: A retrospective analysis of data of patients aged ≥70 years admitted to a palliative care in-patient unit. The agreement between C-G, MDRD, and BIS1 equations was assessed with Bland-Altman analysis. Partial correlation analysis was used to analyze factors influencing the discordance., Results: A total of 174 patients (67 men; mean age 77.9±5.8 years) were enrolled. The mean Δ MDRD and C-G was 18.6 (95% limits of agreement 55.3 and -18.2). The mean Δ BIS1 and C-G was 6.1 (25.7 and -13.5), and the mean Δ MDRD and BIS1 was 12.5 (40.6 and -15.6). According to the National Kidney Foundation classification, 61 (35.1%) patients were differently staged using MDRD and C-G, whilê20% of patients were differently staged with BIS1 and C-G and MDRD and BIS1. Serum creatinine (SCr) and body mass index (BMI) had the most important influence on variability of Δ MDRD and C-G (partial R 37.7% and 28.4%). Variability of Δ BIS1 and C-G was mostly influenced by BMI (34.8%) and variability of Δ MDRD and BIS1 by SCr (42.2%). Age had relatively low influence on differences between equations (3.1%-9.5%).2 37.7% and 28.4%). Variability of Δ BIS1 and C-G was mostly influenced by BMI (34.8%) and variability of Δ MDRD and BIS1 by SCr (42.2%). Age had relatively low influence on differences between equations (3.1%-9.5%)., Conclusion: There is a considerable disagreement between renal function estimation formulas, especially MDRD and C-G in geriatric palliative care patients, which may lead to errors in drug dosage adjustment. The magnitude of discrepancy increases with lower SCr, lower BMI, and higher age., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: In this paper we evaluated the relationship between trough DAB concentration with eGFR calculated using CRE and CYS based formulas., Materials and Methods: We considered 100 patients. eGFR was calculated using CKD-EPIcreat, CG, MDRD, CKD-EPIcys and CKD-EPIcombined equations. DAB dosage was selected on the basis of CKD-EPIcreat and relationship between trough DAB concentration and eGFRs was evaluated., Results: Trough DAB concentration roughly correlates with eGFR calculated using various formulas. CKD-EPIcreat eGFR was higher than CKD-EPIcys. In patients receiving a DAB dosage considered adequate using CKD-EPIcreat eGFR but considered excessive using CKD-EPIcys, we observed higher DAB trough concentration and an increased prevalence of subjects with drug concentration >200ng/mL., Conclusion: These results suggest that eGFR alone was unable to fully explain trough DAB plasma concentration. Therefore a drug's prescription schedule based on eGFR only should be inadequate. We observed a better correlation between trough DAB concentration and CKD-EPIcys rather than CKD-EPIcreat eGFR. Thus, in patients chronically treated with DAB for thromboprophylaxis in nonvalvular atrial fibrillation evaluation of eGFR using a cystatin base formula should be considered., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The recent guideline for the evaluation and management of Chronic Kidney Disease recommends assessing GFR employing equations based on serum creatinine; despite this, creatinine clearance 24-hour urine collection is used routinely in many settings. In this study we compared the classification assessed from CrCl (creatinine clearance 24h urine collection) and e-GFR calculated with CKD-EPI or MDRD formulas., Design and Methods: In this retrospective study we analyze consecutive laboratory data: creatinine clearance 24h urine collection, serum creatinine and demographic data such as sex and age from 15,777 patients >18 years of age collected from 2011 to 2013 in our laboratory at Careggi Hospital. The results were then compared to the estimated GFR calculated with the equations according to the recent treatment guidelines. Consecutive and retrospective laboratory data (creatinine clearance 24h urine collection, serum creatinine and, demographic data such as sex and age) from 15,777 patients >18 years of age seen at Careggi Hospital were collected., Results: Comparison between e-GFR calculated with CKD-EPI or MDRD formulas and GFR according CrCl determinations and bias [95% CI] were 11.34 [-47,4/70.1] and 11.4 [-50.2/73] respectively. The concordance for 18/65 years aged group when compared with e-GFR classification between MDRD vs CKDEPI, MDRD vs CrCl and CKD-EPI vs CrCl were 0.78, 0.34, and 0.41 respectively, while in the 65/110years aged group the concordance Kappas were 0.84, 0.38, and 0.36 respectively., Conclusions: The use of CrCl provides a different classification than the estimation of GFR using a prediction equation. The CrCl is unreliable when it is necessary to identify CKD subjects with decrease of GFR of 5ml/min/1.73m(2)/year., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m² should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m², both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m². Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m² with MDRD and 120 mL/min/1.73 m² with CKD-EPI equation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Creatinine determination in serum is a key indicator of kidney glomerular function. A reference measurement system for its standardization is available and virtually all IVD manufacturers have aligned their assays to this system. In this study, we verified the impact of these standardization efforts on the results of an Italian EQAS involving about 430 laboratories., Method: We considered data obtained during 2006, 2010 and 2011 schemes of EQAS Prolarit for control materials with target values assigned by a traceable method (enzymatic assay calibrated against the NIST SRM 967)., Results: The results showed a good alignment at concentrations ~170μmol/L, with 2011 results - except for one method group - well inside the desirable bias (±4%). At higher concentrations, whereas the bias was small in 2010, for some groups using alkaline-picrate (AP) methods it became significantly negative in 2011. The performance seems to worsen when measuring physiologic concentrations, where a significant positive bias (up to ~20%) is shown by most of the AP-based analytical systems. With few exceptions, no evident improvement in individual assay bias was noted from pre- (2006) to post-standardization (2011) periods. The enzymatic method groups were the only always presenting an acceptable bias at all creatinine concentrations, also showing the lowest between-laboratory variability., Conclusion: Our data seem to indicate that the standardization efforts are still having effects lower than expected. Even taking into consideration that some of the bias may derive from non commutability problems, most of the current "standardized" AP-based methods, at the lower creatinine concentrations, seem to present accuracy problems. This inaccuracy can adversely impact the estimation of GFR by equations and the evaluation of kidney function in pediatrics., (© 2013.)

Objectives: The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals., Design and Methods: Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method., Results: Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results., Conclusion: Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. Methods: One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. Results: Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II–V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. Conclusions: Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents. [ABSTRACT FROM AUTHOR]

Background Glomerular filtration rate (GFR) is commonly used to monitor chronic kidney disease (CKD) progression, but its validity for evaluating kidney function changes over time has not been comprehensively evaluated. We assessed the performance of creatinine-based equations for estimating GFR slope according to patient characteristics and specific CKD diagnosis. Methods In the NephroTest cohort study, we measured GFR 5324 times by chromium 51–labeled ethylenediamine tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1–4 referred to nephrologists (Stages 1–2, 19%) and simultaneously estimated GFR with both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass spectrometry traceable creatinine; absolute and relative GFR slopes were calculated using a linear mixed model. Results Over a median follow-up of 3.4 [interquartile range (IQR) 2.0–5.6] years, the decline in mean absolute and relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 ± 1.2, 1.5 ± 1.4 and 1.3 ± 1.3 mL/min/1.73 m2/year and 5.9 ± 5.3, 5.3 ± 5.3 and 4.8 ± 5.2%/year, respectively; 52% and 55% of the patients had MDRD and CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to overestimate the GFR slope in the youngest patients and underestimate it in the oldest, thus producing inverse associations between age and mGFR versus eGFR slope. Other patient characteristics and specific CKD diagnoses had little effect on the performance of the equations in estimating associations. Conclusions This study shows little bias, but poor precision in GFR slope estimation for both MDRD and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due to variations in muscle mass over time, with implications for clinical care and research. [ABSTRACT FROM AUTHOR]

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Renal function is the most commonly applied patient‐specific quantitative variable used to determine drug doses. Measurement of renal function is not practical in most clinical settings; therefore, clinicians often rely on estimates when making dosing decisions. Similarly, renal function estimates are used to assign subjects in phase 1 pharmacokinetic studies, which inform dosing in late‐phase clinical trials and ultimately the product label. The Cockcroft‐Gault estimate of creatinine clearance has been the standard renal function metric; however, this paradigm is shifting toward the Modification of Diet in Renal Diseases (MDRD) estimate of the glomerular filtration rate (GFR). The proportion of approved new drug labels with dosing recommendations based on the MDRD equation was 16.7% in 2015, 70.0% in 2016, and 46.7% in 2017. Disharmonious recommendations from the United States Food and Drug Administration and the European Medicines Agency will continue to increase this heterogeneity in the assessment of renal function in drug development and negatively impact industry, health systems, and clinicians. In this review, we discuss the current regulatory guidance for the conduct of renal impairment pharmacokinetic studies and review the implications of this guidance across the medication use system with 3 recently approved antibiotics: ceftazidime/avibactam, delafloxacin, and meropenem/vaborbactam. Finally, we suggest measuring GFR in phase 1 studies and employing the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation to integrate data across clinical trials. This will help to harmonize CKD staging, population pharmacokinetic analyses, and dosing by estimated renal function. [ABSTRACT FROM AUTHOR]

Reporting of the estimated glomerular filtration rate (GFR) in every creatinine test is suggested, despite the fact that every laboratory reports it in their result. Modification of Diet in Renal Disease (MDRD) is a formula that is used to estimate the GFR using serum creatinine. Serum cystatin C is a relatively new test and superior for assessing kidney functions. The purpose of this study was to show the correlation between MDRD and serum cystatin C. A cross-sectional study was conducted using secondary data from 260 subjects, aged 40–70 years old to assess serum creatinine and serum cystatin C at a private laboratory in West Jakarta, during the period of January 2013–September 2014. The result of the study showed that the mean age of subjects was 55.7+7.8 years old, the mean serum cystatin C level was 0.99 + 0.6 mg/L, and the mean MDRD was 80.24±28.1 mL/min/1.73 m2. Pearson correlation analysis showed a negative correlation between MDRD and serum cystatin C with r = -0.767 and p =0.001. In conclusion, higher MDRD presents lower cystatin C serum; hence, MDRD can be used as an alternative renal function test when serum cystatin C is not available. [

Background: The evaluation of chronic kidney disease (CKD) in cancer patients seems to rely mostly on the Cockcroft‐Gault (CG) formula or the creatinine levels to adjust treatment dosages which is a practice refuted by internists. Aims: We evaluate the overall agreement of the CG, modification of diet in renal disease (MDRD) and CKD–epidemiology collaboration equations (CKD‐EPI) equation with the newly devised Janowitz and Williams' (JW) equation. Methods: The renal function was estimated in 235 cancer patients according to the CG, MDRD, body surface area (BSA)‐adjusted MDRD, CKD‐EPI, BSA‐adjusted CKD‐EPI and JW formulae. Results: JW equation was more in agreement with CG and CKD‐EPI estimations than the other equations. Taking JW equation as reference, receiver operating characteristic curve analysis showed that CG eGFR had the higher area under the curve when compared with other equations. Hierarchical cluster analysis showed more proximity between CG and JW equations than the other equations. Conclusion: The newly proposed JW eGFR estimation was more in agreement with CG equation than the other equations. [ABSTRACT FROM AUTHOR]

Résumé Le débit de filtration glomérulaire est le meilleur marqueur quantitatif de fonction rénale. Il permet le diagnostic et la classification en cinq stades de gravité de la maladie rénale chronique. La mesure du débit de filtration glomérulaire repose en théorie sur le calcul de la clairance urinaire de substances exogènes telles l’inuline ou l’éthylène-diamine-tétra-acétique acide marqué au chrome 51. En pratique, le débit de filtration glomérulaire est le plus souvent estimé à partir d’équations dérivées de la créatinine plasmatique. Ce travail passe en revue l’ensemble des méthodes destinées à mesurer ou approcher le débit de filtration glomérulaire, et s’attache à décrire les évolutions récentes dans ce domaine, incluant celles concernant les méthodes de dosage de la créatinine plasmatique, les estimateurs dérivés de la concentration de créatinine et de la cystatine. La place de la mesure du débit de filtration glomérulaire par clairance de traceurs exogènes est également discutée. Glomerular filtration rate is the best quantitative marker of renal function. It allows diagnosis and classification of severe chronic kidney disease into five stages. Theoretically, the measurement of glomerular filtration rate is based on the calculation of urinary clearance of exogenous substances such as chromium 51-labeled inulin or ethylenediaminetetraacetic acid ([ 51 Cr]-EDTA). In practice, glomerular filtration rate is most often estimated from equations derived from plasma creatinine. This article reviews the range of methods used to measure or approximate glomerular filtration rate and attempts to describe recent developments in this area, including those related to plasma creatinine assay methods, creatinine and cystatin C concentration-derived estimations. Measurement of glomerular filtration rate by the clearance of exogenous tracers is also discussed. [ABSTRACT FROM AUTHOR]

Background: In acutely unwell patients with rapidly changing renal function, estimating glomerular filtration rate (GFR) and predicting adverse renal outcomes are challenging and often inaccurate. Kinetic GFR (kGFR) is an estimate of immediate biomarker clearance derived from two discreet measurements that may better represent acute function. Our objective is to assess the clinical utility of kGFR as a predictive tool and examine the association of kGFR to adverse renal outcomes compared with measurements to traditional estimates. Methods: We compared the association of kGFR and Modification of Diet in Renal Disease (MDRD) with acute kidney injury (AKI), renal replacement therapy (RRT), cardiovascular morbidity, 30-day mortality and new chronic kidney disease development. A total of 107 acute admissions to a medical high dependency and intensive care unit were assessed retrospectively. Creatinine measurements and outcomes were recorded and kGFR was calculated at the earliest possible time point. This was then compared with simultaneous MDRD estimated GFR. Results: Mean age was 60 years old, AKI occurred in 25% of patients, acute cardiovascular events occurred in 13%, RRT was initiated in 15% and 30-day mortality was 30%. kGFR predicted the AKI more accurately than MDRD [area under the receiver operating characteristic curve (AUC) = 0.86 versus AUC = 0.64]. kGFR predicted the need for RRT more accurately than MDRD (AUC = 0.901 versus AUC = 0.79). Neither kGFR nor admission MDRD was associated with 30-day mortality or cardiovascular morbidity. Conclusions: Measuring kGFR in the acute setting could help clinicians better predict adverse renal outcomes. [ABSTRACT FROM AUTHOR]

Glomerular filtration rate (GFR) measurements are critical in patients with hepatic cirrhosis but potentially erroneous when based on serum creatinine. New equations for estimated GFR (eGFR) have shown variable performance in cirrhotics, possibly because of inaccuracies in reference methods for measured GFR (mGFR). The primary objective was to compare the performance of 4 improved eGFR equations with a 1-compartment, 2-sample plasma slope intercept 99mTc-DTPA mGFR method to determine whether any of the eGFR calculations could replace plasma 99mTc-DTPA mGFR in patients with cirrhosis. The secondary objective was to test the hypothesis that mGFR using voluntary voided urine collections introduces error compared with plasma-only methods. Methods: Fifty-four patients with hepatic cirrhosis underwent mGFR determinations from 2 plasma samples at 1 and 3 h after intravenous administration of 185 MBq of 99mTc-DTPA. GFR was also generated by a UV/P calculation derived from blood and urine samples. These mGFRs were compared with the eGFRs generated by 4 estimating equations: MDRD (Modified Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) (serum creatinine [SCr]), CKD-EPI (cystatin [CysC]), and CKD-EPI (CysC+SCr). eGFRs were compared with mGFRs by Pearson correlation, precision, bias, percentage bias, and accuracy (eGFRs varying by <10% [p10], <20% [p20] or <30% [p30] from the corresponding mGFR). Results: All eGFRs showed poorer performance when the UV/P 99mTc-DTPA mGFR was used as the reference than when the plasma 99mTc-DTPA mGFR was used. When compared with the plasma 99mTc-DTPA mGFR method, the performance of all eGFR equations was superior to most published reports. There was a moderately good positive correlation between eGFRs and mGFRs. When compared with plasma 99mTc-DTPA mGFR, precision of eGFRs was in the range of 14-20 mL/min and showed a negligible bias. Compared with the plasma 99mTc-DTPA mGFR, CKD-EPI (CysC+SCr) showed the best overall performance and accuracy, at 85.19% (p30), 75.93% (p20), and 42.59% (p10). Conclusion: Estimating equations for measuring eGFR performed better than in most published reports, attributable to use of the plasma 99mTc-DTPA mGFR method as a reference. CKD-EPI (CysC+SCr) eGFR showed the best overall performance. However, more discriminating methods may be required when accurate GFR measurements are necessary. mGFR measurements using urine collections may introduce error compared with plasma-only methods. [ABSTRACT FROM AUTHOR]

IntroductionAssessment of renal function based on quantification of the glomerular filtration rate (GFR) is essential for early detection of damage and progression of renal diseases. The purpose of our study was to determine the value of cystatin C (Cys C) assays in the calculation of the GFR and bioelectrical impedance analysis parameters in obese subjects aged 30-70 years with moderately damaged renal function.Materials and methodsCys C levels were measured with a new immunoturbidimetric kit (Roche Diagnostics) and an automated Cobas c6000 analyzer. In the GFR calculation, creatinine and Cys C levels were included. The GFR calculated with the equation that included Cys C in obese and normal-weight patients is not affected by changes in the lean body mass.ResultsObese patients (N = 70) had a mean (± SD) serum creatinine level of 1.52 ± 1.0 mg/dL and a mean Cys C level of 1.28 ± 0.59 mg/L. In this group, the GFR calculated on the basis of MDRD, Cys C, and creatinine clearance values showed similar filtered values between MDRD and Cys C and a DS value smaller in the case of Cys C. The correlation (R2) between GFR and its metabolite is higher in the case of Cys C when somatotype parameters (measured with bioelectrical impedance analysis) were introduced into the equation.ConclusionsWhen Cys C is included in calculations of GFR, the result shows a higher correlation degree compared to the MDRD system. Given that Cys C shows less intra-individual variability than creatinine, it can be applied in routine diagnostics in a larger number of patients.

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Background: This paper aims to evaluate, in a clinical context, current creatinine-based formulas commonly used to calculate renal function in morbidly obese patients. Methods: A retrospective analysis was performed of the estimates of renal function of 63 obese or morbidly obese patients undergoing gastric bypass surgery. Each patient's glomerular filtration rate (GFR) was calculated using five methods, both before and after surgery, and these approximations were then compared. Results: Prior to surgery, the values offered by the five formulas for the renal function of this population ranged widely, by over a factor of 2. After surgery, the three weight-based GFR estimation methods indicated that a significant change in GFR had occurred, but the two non-weight-based formulas showed no significant change in estimated GFR. Conclusions: At baseline and after significant weight loss, creatinine-based formulas differ twofold in their estimates of renal function of the morbidly obese. An accurate method for calculating these patients' renal function is required to improve patient safety with drug dosing as well as to ensure early detection of renal failure. [ABSTRACT FROM AUTHOR]

Background: In renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae. Methods: In 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses. Results: Reasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m2]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods. Conclusions: For routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73m2] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination. [ABSTRACT FROM AUTHOR]

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Chronic kidney disease (CKD) is an important epidemic and public health problem that is associated with a significant risk for vascular disease and early cardiovascular mortality as well as progression of kidney disease. Currently it is classified into five stages based on the glomerular filtration rate (GFR) as recommended by many professional guidelines. Radiolabelled methods for measuring GFR are accurate but not practical and can be used only on a very limited scale while the traditional methods require timed urine collection with its drawback of inaccuracy, cumbersomeness and inconvenience for the patients. However, the development of formula- based calculation of estimated GFR (eGFR) has offered a very practical and easy approach for converting serum creatinine value into GFR result taking into consideration patient's age, sex, ethnicity and weight (depending on equation type). The commonly used equations include Cockraft and Gault (1976), Modification of Diet in Renal Disease (MDRD) (1999) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009). It is the implementation of these equations particularly the MDRD that has raised the medical awareness in the diagnosis and management of CKD and its adoption by many guidelines in North America and Europe. The impact and pitfalls of each of these equations in the screening, diagnosis and management of patients with CKD are presented and discussed in this review. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Assessment of renal function based on quantification of the glomerular filtration rate (GFR) is essential for early detection of damage and progression of renal diseases. The purpose of our study was to determine the value of cystatin C (Cys C) assays in the calculation of the GFR and bioelectrical impedance analysis parameters in obese subjects aged 30-70 years with moderately damaged renal function. Materials and methods: Cys C levels were measured with a new immunoturbidimetric kit (Roche Diagnostics) and an automated Cobas c6000 analyzer. In the GFR calculation, creatinine and Cys C levels were included. The GFR calculated with the equation that included Cys C in obese and normal-weight patients is not affected by changes in the lean body mass. Results: Obese patients (N=70) had a mean (± SD) serum creatinine level of 1.52±1.0 mg/dL and a mean Cys C level of 1.28±0.59 mg/L. In this group, the GFR calculated on the basis of MDRD, Cys C, and creatinine clearance values showed similar filtered values between MDRD and Cys C and a DS value smaller in the case of Cys C. The correlation (R2) between GFR and its metabolite is higher in the case of Cys C when somatotype parameters (measured with bioelectrical impedance analysis) were introduced into the equation. Conclusions: When Cys C is included in calculations of GFR, the result shows a higher correlation degree compared to the MDRD system. Given that Cys C shows less intra-individual variability than creatinine, it can be applied in routine diagnostics in a larger number of patients. [Copyright &y& Elsevier]

The purpose of this study was to determine the number of prescribed antibiotics being appropriately adjusted and to assess antibiotics with the highest incorrect dosing based on the patient's renal function according to distinguished guidelines. The study was conducted at a 446-bed university hospital. One hundred and fifty patients admitted through different wards of the hospital were included in the study. Demographic data were extracted and creatinine clearance was calculated using either Cockcroft-Gault (C&G) or Modification of Diet in Renal Disease (MDRD) formula. In patients with creatinine clearances less than 50 mL/min, antibiotic dosages were compared with guideline dose recommendations to judge whether they were correctly adjusted. Two hundreds and ninety-one instructions (79.9%) of 364 antibiotic prescriptions required dosage adjustment based on the patient's renal condition. These adjustments were rationally performed in 43.7% and 61.4% of prescriptions, according to the two guidelines used. Ciprofloxacin (29.1% of cases), and vancomycin (33.6% of cases), were the most inappropriate prescribed antibiotics in terms of dose administration. Drug dosing adjustments should be emphasized in patients with renal dysfunction. Failure to do so may lead to higher morbidity and mortality as well as therapeutic costs. Estimating creatinine clearance prior to drug ordering and use of a reliable dosing guideline is highly recommended. [ABSTRACT FROM AUTHOR]

Background. Over the past decade, chronic kidney disease (CKD) has become an area of intensive clinical and epidemiological research. Despite the clarity provided by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, there appears to be within the CKD research literature significant disagreement on how to define CKD and measure kidney function.Methods. The objectives of this study were to investigate the variety of methods used to define CKD and to measure kidney function in original research papers as well as to investigate whether the quality of the journal had any effect on the quality of the methodology used.This was a descriptive review and not a meta-analysis. Information was extracted from each article including publication details (including the journal's impact factor), definition of CKD, method used to estimate kidney function and quantity of serum creatinine readings used to define CKD.An electronic search of MEDLINE through OVID was completed using the search term CKD. The search was limited to articles in English published in 2009.Studies were included in the review only if they were original research articles including patients with CKD. Articles were excluded if they reported data from a paediatric population, a population solely on dialysis or if there was no full-text access through OVID.Each article was assessed for quality with respect to using KDOQI CKD definition criteria.A description of the pooled data was completed and chi-square tests were used to investigate the relation between article quality and journal quality. Analysis was carried out using SPSS (15.0) and a P-value of <0.05 was considered to indicate statistical significance.Results. The final review included 301 articles. There were a variety of methods used to define CKD in original research articles. Less than 20% (n = 59) of the articles adhered to the established international criteria for defining CKD. The majority of articles (52.1%) did not indicate the quantity of serum creatinine measurements used to define CKD. The impact factor or specialist nature of the scientific journal appears to have no bearing on whether or not published articles use the gold standard KDOQI guidelines for labelling a patient with a diagnosis of CKD.Conclusions. This review of literature found that a variety of definitions are being used in original research articles to define CKD and measure kidney function which calls into question the validity and reliability of such research findings and associated clinical guidelines. International consensus is urgently required to improve validity and generalizability of CKD research findings. [ABSTRACT FROM PUBLISHER]

Background. Serum creatinine (S-Cr)-based prediction equations are commonly used for estimating glomerular filtration rate (GFR). However, S-Cr concentration is also affected by other factors such as tubular secretion, muscle mass, diet, gender and age. Serum cystatin C (S-Cys C)-based prediction equations have been proposed as an improved potential alternative as S-Cys C levels are not influenced by many of the factors that affect creatinine concentration other than GFR. This may be of great benefit to patients with low muscle mass such as those infected with human immunodeficiency virus who are at increased risk for the development of renal impairment. The aim of this study was to develop and evaluate a S-Cys C-based prediction equation for different stages of renal disease in black South Africans.Methods. One hundred patients with varying degrees of renal function were enrolled in the study. The plasma clearance of 51Cr-EDTA, a gold standard method, was used to measure GFR (mGFR). In addition, serum was analysed for S-Cr and S-Cys C on each participant. This dataset was split into a development dataset (n = 50) and a test dataset (n = 50). The development dataset was used to formulate a S-Cys C- and S-Cr-based prediction equation using multiple linear regression analysis. These equations together with the four-variable MDRD and CKD-EPI equation were then tested on the test dataset.Results. In the test dataset, accuracy within 15% of measured GFR was 68% for the S-Cys C equation and 48% for the S-Cr equation. Root mean square error for S-Cr eGFR was 10.7 mL/min/1.73 m2 for those patients with mGFR < 60 mL/min/1.73 m2 and 25.5 mL/min/1.73 m2 for those patients with mGFR > 60 mL/min/1.73 m2. Root mean square error for S-Cys C eGFR was 10.2 mL/min/1.73 m2 for those patients with mGFR < 60 mL/min/1.73 m2 and 11.9 mL/min/1.73 m2 for those patients with mGFR > 60 mL/min/1.73 m2.Conclusions. In this study, S-Cys C-based prediction equations appear to be more precise than those of S-Cr for those patients with mGFR > 60 mL/min/1.73 m2 and may therefore be of benefit in the earlier detection of renal impairment. [ABSTRACT FROM AUTHOR]

Background. Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients. Methods. Retrospective observational study was performed, on patients treated within the general intensive care unit (ICU) during 2004-2006, in a Swedish university hospital. Results. GFR markers are frequently ordered in the ICU; 92% of the patient test results had cystatin C-estimated GFR (eGFRcystatinC) ≤80 mL/min/1.73 m2, 75% had eGFR ≤ 50 mL/min/1.73 m2, and 30% had eGFR≤ 20 mL/min/1.73 m2. In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFRMDRD≤ 80 mL/min/1.73 m2. The mean difference between eGFRMDRD and eGFRcystatinC was 39 mL/min/1.73 m2 for eGFRcystatinC values ≤ 60 mL/min/1.73 m2 Conclusions. GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFRMDRD. Many pharmaceuticals are eliminated by the kidney, and their dosage is adjusted for kidney function. Thus, the differences in GFR estimates by the methods used indicate that the GFR method used in the intensive care unit may influence the treatment. [ABSTRACT FROM AUTHOR]

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In sports medicine, creatinine is used for evaluating general health status of athletes. In the present review, different aspects of the behaviour of creatinine values in sportsmen are summarized. The reference values for common biochemical and haematological parameters used for athletes are the same commonly used for general population. The serum concentration of creatinine could sometimes apparently pathological in some athletes and the interpretation of these values should consider the sportsmen status. In fact, the values of serum creatinine in athletes are higher than those reported in sedentary people. However, the population of sportsmen is not homogeneous, and some differences are evident among athletes competing in different sport disciplines. The creatinine values are affected from acute exercise, which modifies renal flow. The sport discipline is an additional variable for interpreting creatinine values, which can show values lower than those measured in sedentary people in endurance athletes. The creatinine values are modified in some sport disciplines during competitive season, showing increases when activity is more intense. Cystatin C, a low molecular weight that is freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, could be used in athletes, while it is virtually independent from body mass. [ABSTRACT FROM AUTHOR]

The article details a study which examined if creatinine clearance can be estimated by clearance of gentamicin/tobramycin and non-invasive estimates in the intensive care unit. The study included 100 patients in the intensive care unit whose renal function were examined. Study authors concluded that gentamicin/tobramycin is a good estimate of creatinine clearance. However, they noted that two-hour urine and MDRD4 estimates should not be applied in the intensive care unit.

Background: Serum creatinine-based estimates of GFR may be inaccurate in the elderly and there is need for improvement. Serum Cystatin C, not being influenced by muscle volume, may be more accurate. Material and methods: GFR was measured with plasma clearance of iohexol in 50 elderly persons aged >70 years. Blood tests were drawn for analysis of creatinine, albumin and urea. Cystatin C was analysed on frozen specimens using the Dade Behring method. GFR estimates based on cystatin C were compared to estimates based on serum creatinine, using earlier published equations. Results: Significant increase with age was found with cystatin C (rs=0.62, p=0.0001) and urea (rs=0.43, p=0.0018) but no correlation with creatinine (rs=0.05, p=0.7502). All equations underestimated GFR with a bias ranging from −2.2 to −31%. The equation with the greatest accuracy was the Hoek equation (Cystatin C based) with 98% of estimates within 30% of mGFR and confidence interval 89-100%. Estimated GFR using the MDRD Study equations (creatinine based) showed accuracy of 94% with 4 or 6 factors used. There was a gender difference with an accuracy higher among males ( p<0.002). The Cockcroft Gault equation was not found useful with high bias and a low accuracy. Conclusion: S-cystatin C seems a useful marker for kidney function in the elderly. Two equations based on serum cystatin C as well as the two MDRD equations seem adequate for estimating kidney function. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prognostic value of cystatin C relative to glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease Study (MDRD) equation modified for Japan has not been investigated in acute heart failure patients with normal to moderately impaired renal function. More accurate detection of mild renal impairment might improve the risk stratification of heart failure patients, especially patients with normal to moderately impaired renal function. Methods: Cystatin C and creatinine levels were measured on admission in 328 consecutive patients hospitalized for worsening chronic heart failure with a GFR estimated by MDRD equation modified for Japan ≥30 mL/min/1.73 m2. Results: During a median follow-up period of 915 days, there were 52 (16%) cardiac deaths. In stepwise Cox regression analyses including cystatin C and GFR estimated by MDRD equation modified for Japan (either as continuous variables or as variables categorized into quartiles), cystatin C (P <.0001), but not GFR estimated by MDRD equation modified for Japan, was independently associated with cardiac mortality. Adjusted relative risk according to the quartiles of these markers and Kaplan-Meier analyses revealed that the cystatin C was a better marker to separate low-risk from high-risk patients. Furthermore, receiver-operating characteristic curve analyses of these markers revealed that cystatin C showed a higher precision in predicting cardiac mortality. Conclusion: Measurements of cystatin C might improve early risk stratification compared with GFR estimated by MDRD equation modified for Japan in acute heart failure patients with normal to moderately impaired renal function. [Copyright &y& Elsevier]

Background: In clinical practice, the glomerular filtration rate (GFR) is routinely estimated by the creatinine-based equation developed and validated from the Modification of Diet in Renal Disease (MDRD) Study. However, since this formula estimates the rate of decline in GFR, the Mayo Clinic Quadratic Equation (MCQE) has been developed. Petients and methods: The purpose of this study was to assess the influence of age and gender variations on GFR estimated by this new equation. Results of 16,631 serum creatinine tests performed in consecutive outpatients were retrieved from the database of our Laboratory Information System. GFR was estimated by both the MDRD and MCQE formulas. Results: The difference in the estimated GFR between males and females was significantly different when calculated with either MDRD or MCQE formula. Significant gender differences were observed in all age decades by MCQE and in subjects aged >51 years by MDRD. A significant difference in the mean GFR values estimated by either formula was also observed between different age decades in both genders. Conclusions: The results of this epidemiological analysis indicated the MCQE formula also fail to compensate for age and gender variations. [ABSTRACT FROM AUTHOR]

Abstract: Background: Accurate assessment of renal function in patients with cystic fibrosis (CF) is vital for determining the appropriate dose of medications and for early detection of renal disease. Cystatin C (CysC) is a new marker of GFR with reportedly improved accuracy and precision compared to methods incorporating serum creatinine. The purpose of this study is to evaluate the predictive performance of cystatin C in estimating GFR in adult patients with CF. Methods: Iothalamate was administered to enable measurement of GFR in 38 adult patients with CF and control subjects. Creatinine clearance (C&G) and GFR estimates (cystatin C clearance [Cys C] and abbreviated modified diet in renal disease [aMDRD]) were compared using Bland–Altman and receiver operating characteristic (ROC) analysis. GFR cutoff values of 80 and 90 mL/min–1.73 m2 were used in the analysis. Results: The measured GFR was similar in both the CF and healthy volunteers 104 (32.2) and 105 (29.9), P =0.969 respectively. No significant difference in mean bias was noted between the predictive methods within the CF population. Cys C provided the most precise estimates of GFR in both populations. ROC curves demonstrated that CysC provided greater sensitivity and specificity compared to the aMDRD (AUC 0.93 vs. 0.54, P =0.003) and C&G (AUC 0.93 vs. 0.56, P =0.005) in CF at a cutoff GFR of 90 mL/min–1.73 m2. Conclusion: Cystatin C clearance provides an improved marker of glomerular filtration rate in CF patients. [Copyright &y& Elsevier]

The estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease and for the treatment of patients with medications that are eliminated by the kidneys. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of GFR. However, there is limited information on the circadian variation of cystatin C and estimated GFR using cystatin C (eGFRCystC) or “The Modification of Diet in Renal Disease Study” (MDRD) (eGFRMDRD) equations. We studied the circadian variation of cystatin C and creatinine during night- and day-sleep conditions in seven healthy volunteers. Serum samples were collected every hour (48 samples per individual) to evaluate the effect of different sampling times on the test results. The median intra-individual coefficients of variations for the studied markers were 4.2% for creatinine, 4.7% for eGFRMDRD, 5.5% for cystatin C, and 7.7% for eGFRCystC. Neither cystatin C nor creatinine differed significantly between the night- and day-sleep conditions. Cystatin C differed significantly with time of day (p=.0003), but this was not the case for creatinine (p=.11). The circadian variation of cystatin C was minor. Small but significant increases in creatinine values and a decrease of eGFRMDRD were observed after food intake. Thus, cystatin C and creatinine sampling does not have to be restricted to specific times of the day. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease, and for correct dosage of drugs that are eliminated from the circulation by the kidneys. In most cases GFR is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula. As both cystatin C and creatinine are used for the determination of GFR it is important to investigate if estimated GFR by the two methods differ in various patient groups. Design and methods: We have compared cystatin C and MDRD estimated GFR calculated from the same request from primary care units (n =488), a cardiology ward (n =826), the cardiointensive care unit (n =1026), two oncology wards (n =919 and 1021), and the neurosurgical intensive care unit (n =1515) in an observational cross-sectional study. Results: We found better agreement between the two GFR estimates in samples from primary care patients and patients in the cardiology wards, than in samples from oncology wards or the neurosurgical intensive care unit. In the latter settings there was a pronounced difference between the two GFR estimates. Conclusion: The comparisons show that differences in patient selections have a strong impact on the agreement between cystatin C and MDRD estimated glomerular filtration rate. [Copyright &y& Elsevier]

Regarding the prevalence of chronic kidney disease in the population, estimation of glomerular filtration rate is of importance. Creatinine-based formulas are thus useful as the first step of a prevention strategy. Several creatinine-based formulas have been published. Among these, the Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) study equation are the most used by physicians. The latter may be automatically reported by laboratories and has thus great success. However, these formulas have limitations. First, the MDRD formulas are not applicable to all populations, notably the healthy one and the patients with abnormal weight (anorectic or obese). Second, we evoke the limitations in the precision of the formulas linked to analytical aspects. Indeed, these analytical limitations remain significant even if they are improved by creatinine standardization. Lastly, we briefly mention the potential impact of these limitations on the epidemiology and the staging of chronic kidney disease. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr1yr) and MDRD estimated glomerular filtration rate measured at one year (eGFRMDRD1yr) as predictors of graft survival. Data on 1,110 patients who received a renal transplant between 1989 and 2005 were extracted from the Irish Renal Transplant Registry. The study group was divided into quartiles of patient numbers according to SCr1yr and eGFRMDRD1yr. Kaplan-Meier estimates of the primary end-point graft survival were constructed for each quartile. Additionally, a Cox Regression restricted cubic spline model was performed for both eGFRMDRD1yr and SCr1yr. Both overall graft outcome and outcome censored for death with a functioning graft (CDWFG) were used as endpoints. Cox regression analysis was performed along with tests for the proportionality assumption to compare the predictive value of eGFRMDRD1yrand SCr1yr. Both eGFRMDRD1yr and SCr1yr were independently associated with long-term renal transplant survival. eGFRMDRD1yr and SCr1yr had similarly strong associations with long-term outcome when the quartile variables were compared using the Bayesian Information Criterion method. The Cox regression restricted cubic spline modeling demonstrated that an eGFRMDRD1yr value < 27 mLs/min/1.73m2 and a SCr1yr value > 229 μmol/L were associated with poor graft survival. [ABSTRACT FROM AUTHOR]

Background The accuracy of measuring serum cystatin C levels for detecting various stages of chronic kidney disease (CKD) in diabetes is still unclear. Methods In a cross-sectional study of 251 subjects, a reference glomerular filtration rate (GFR) was measured using 99cTc-DTPA plasma clearance (iGFR). Multivariate analysis was used to identify independent clinical and biochemical associations with serum cystatin C and iGFR levels. The diagnostic accuracy of cystatin C and commonly used creatinine-based methods of measuring renal function (serum creatinine, the MDRD four-variable and Cockcroft–Gault formulae) for detecting mild and moderate CKD was also compared. Results In the entire study population the same five variables, age, urinary albumin excretion rates, haemoglobin, history of macrovascular disease and triglyceride levels were independently associated with both cystatin C and iGFR levels. A serum cystatin C level cut-off > 82.1 nmol/l (1.10 mg/l) had the best test characteristics as a screening tool for detecting moderate CKD (< 60 ml/min per 1.73 m2) when compared with creatinine-based methods. At the upper threshold for mild CKD (< 90 ml/min per 1.73 m2), cystatin C also had greater diagnostic accuracy than creatinine, but had similar diagnostic accuracy when compared with creatinine-based formulae for predicting renal function. Conclusions This study suggests that the clinical and biochemical parameters associated with serum cystatin C levels are closely linked to those associated with GFR and highlights the potential usefulness of screening for moderate or mild CKD in subjects with diabetes by simply measuring serum cystatin C levels. [ABSTRACT FROM AUTHOR]

Background. In this article (the second of two companion studies), we report whether bioelectrical impedance analysis (BIA) can be used to predict muscle mass in patients with chronic kidney disease (CKD), and whether using this predicted muscle mass can improve the estimation of glomerular filtration rate (GFR). [ABSTRACT FROM PUBLISHER]