Measured GFR as "Gold Standard"-All that Glitters Is Not Gold?

Division of Nephrology, University of California, San Francisco, 513 Parnassus Avenue, 672 HSE, Box 0532, San Francisco, CA 94143-0532. .
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 08/2011; 6(8):1813-4. DOI: 10.2215/CJN.06040611
Source: PubMed

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    • "Radiolabelled iothalamate plasma clearance was the method used for developing the Modification of Diet in Renal Disease (MDRD) Study [9] and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [10] GFR-estimating equations (see below), whilst the CKD-EPI equation validation dataset also used a variety of other reference GFR methods including iohexol [10]. Although regarded as the reference approach to assessment of kidney function, it is increasingly appreciated that non-inulin plasma clearance methods are not all equivalent [11]. Furthermore, as with any physiological measurement, GFR has an intrinsic biological variability, the understanding of which is critical to appreciation of disease-related change. "
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    ABSTRACT: Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations.Methods/design: Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components:1)A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of south-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR >=30 mg/mmol) will comprise 20-30% of the study cohort.2)A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3)A biological variability study to establish reference change values for reference and test measures.4)A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5)A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline. The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.Trial registration: ISRCTN42955626.
    Full-text · Article · Jan 2014 · BMC Nephrology
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    ABSTRACT: Among issues susceptible to hamper a reliable measurement of inulin clearance, those regarding the dosage of inulin are largely neglected. We have compared the analytical performances of 2 commonly used methods of inulin dosage (one "acid" and one "enzymatic" method) and studied their potential impact on the glomerular filtration rate (GFR) value given by inulin clearance. Repeatability, uncertainty and the beta-expectation limits were evaluated from pre-determined serum and urine pools of inulin. Agreement between the two methods was analyzed from 99 inulin clearances performed in renal transplant patients. Impact of the method of dosage on GFR evaluation was simulated according to the respective beta-expectations limits of each method. Overall, intra-assay coefficient of variability and relative bias were inferior to 5% and 10% for both methods. Contrary to the acid method, analytical performance of the enzymatic method was not influenced by the presence of glucose. The relative difference in GFR values obtained with the two methods in transplant patients was -0.4 ± 10%. Simulations suggested that changes in inulin concentration attributable to analytical error could modify the value of GFR from -12% to +28%. In conclusion, while analytical performances are globally acceptable for both methods, they are not strictly equivalent. The impact on the determination of GFR, albeit limited, is not negligible and adds to other sources of inaccuracy. International standardization for the dosage of inulin is necessary.
    No preview · Article · Dec 2011 · Clinica chimica acta; international journal of clinical chemistry
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    ABSTRACT: BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.
    No preview · Article · Aug 2012 · American Journal of Kidney Diseases
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