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      International Collaboration for the Epidemiology of eGFR in Low and Middle Income Populations - Rationale and core protocol for the Disadvantaged Populations eGFR Epidemiology Study (DEGREE)

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          Abstract

          Background

          There is an increasing recognition of epidemics of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low- and middle-income countries (LMICs). Although it is currently unclear whether there is a unified underlying aetiology, these conditions have been collectively termed CKD of undetermined cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young men and women over the last 2 decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these condition (s). International comparisons have provided the first steps in understanding many chronic diseases, but such comparisons rely on the availability of standardised tools to estimate disease prevalence. This is a particular problem with CKD, since the disease is asymptomatic until the late stages, and the biases inherent in the methods used to estimate the glomerular filtration rate (GFR) in population studies are highly variable across populations.

          Method

          We therefore propose a simple standardised protocol to estimate the distribution of GFR in LMIC populations – The Disadvantaged Populations eGFR Epidemiology (DEGREE) Study. This involves the quantification of renal function in a representative adult population-based sample and a requirement for standardisation of serum creatinine measurements, along with storage of samples for future measurements of cystatin C and ascertainment of estimates of body composition, in order to obtain valid comparisons of estimated GFR (eGFR) within and between populations.

          Discussion

          The methodology we present is potentially applicable anywhere, but our particular focus is on disadvantaged populations in LMICs, since these appear to be most susceptible to CKDu. Although the protocol could also be used in specific groups (e.g. occupational groups, thought to be at excess risk of CKDu) the primary aim of the DEGREE project is characterise the population distribution of eGFR in multiple regions so that international comparisons can be performed. It is only with a standardised approach that it will be possible to estimate the scale of, and variation in, impaired kidney function between affected areas. These data should then provide insights into important social, demographic and environmental risk factors for this increasingly recognised disease.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12882-016-0417-1) contains supplementary material, which is available to authorized users.

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          Most cited references17

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          Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.

          G. Myers (2006)
          Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 micromol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL.min(-1).(1.73 m2)(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.
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            Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities.

            An equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provides more accurate estimates of the glomerular filtration rate (eGFR) than that from the modification of diet in renal disease (MDRD) Study, although both include a two-level variable for race (Black and White and other). Since creatinine generation differs among ethnic groups, it is possible that a multilevel ethnic variable would allow more accurate estimates across all groups. To evaluate this, we developed an equation to calculate eGFR that includes a four-level race variable (Black, Asian, Native American and Hispanic, and White and other) using a database of 8254 patients pooled from 10 studies. This equation was then validated in 4014 patients using 17 additional studies from the United States and Europe (validation database), and in 1022 patients from China (675), Japan (248), and South Africa (99). Coefficients for the Black, Asian, and Native American and Hispanic groups resulted in 15, 5, and 1% higher levels of eGFR, respectively, compared with the White and other group. In the validation database, the two-level race equation had minimal bias in Black, Native American and Hispanic, and White and other cohorts. The four-level ethnicity equation significantly improved bias in Asians of the validation data set and in Chinese. Both equations had a large bias in Japanese and South African patients. Thus, heterogeneity in performance among the ethnic and geographic groups precludes use of the four-level race equation. The CKD-EPI two-level race equation can be used in the United States and Europe across a wide range of ethnicity.
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              Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2.

              The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics. Test of diagnostic accuracy. Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index. eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine. Measured GFR using urinary or plasma clearance of exogenous filtration markers. Mean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR or=90 mL/min/1.73 m2. Limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation. Copyright (c) 2010 National Kidney Foundation, Inc. All rights reserved.
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                Author and article information

                Contributors
                +44 20 7830 2695 , b.caplin@ucl.ac.uk
                kristina.jakobsson@amm.gu.se
                jason@laislafoundation.org
                Dorothea.Nitsch@lshtm.ac.uk
                vjha@georgeinstitute.org.in
                Ajay_Singh@hms.harvard.edu
                correarotter@gmail.com
                Neil.Pearce@lshtm.ac.uk
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                3 January 2017
                3 January 2017
                2017
                : 18
                : 1
                Affiliations
                [1 ]Centre for Nephrology, UCL Medical School Royal Free, London, NW3 2PF UK
                [2 ]Division of Occupational and Environmental Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
                [3 ]Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
                [4 ]La Isla Foundation, Ada, Michigan USA
                [5 ]Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
                [6 ]George Institute for Global Health India, New Delhi, India
                [7 ]University of Oxford, Oxford, UK
                [8 ]Department of Global and Continuing Education, Harvard Medical School, Boston, USA
                [9 ]Department of Nephrology and Mineral Metabolism at the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, Mexico City, Mexico
                [10 ]Department of Non-Communicable Disease Epidemiology and Centre for Global NCDs, London School of Hygiene and Tropical Medicine, London, UK
                Author information
                http://orcid.org/0000-0001-9544-164X
                Article
                417
                10.1186/s12882-016-0417-1
                5210224
                28049448
                15bb2e1d-722c-4c07-89f7-900574bbf5cf
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 June 2016
                : 9 December 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 097834/Z/11/B
                Categories
                Study Protocol
                Custom metadata
                © The Author(s) 2016

                Nephrology
                chronic kidney disease of undetermined cause,low- and middle-income countries,mesoamerican nephropathy,estimated glomerular filtration rate,chronic kidney disease prevalence

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