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      Causal effects of education on chronic kidney disease: a Mendelian randomization study

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          Abstract

          Background

          Poor socio-economic status, including low education attainment, has been reported in chronic kidney disease (CKD) patients. We aimed to investigate the causal effects of education attainment on the risk of CKD.

          Methods

          The study was an observational cohort study including Mendelian randomization (MR) analysis. First, the clinical association between education attainment years as the exposure and prevalent CKD Stages 3–5 as the outcome was investigated by multivariable logistic regression in 308 741 individuals 40–69 years of age from the UK Biobank. MR analysis was performed with a previously reported genetic instrument from a genome-wide association meta-analysis of education attainment. Two-sample MR was performed with summary statistics for CKD in 567 460 individuals with European ancestry in the CKDGen genome-wide association meta-analysis. The findings were replicated by allele score–based MR in 321 260 individuals of white British ancestry in the UK Biobank with quality-controlled genetic data.

          Results

          Higher education attainment was significantly associated with lower adjusted odds for CKD in the clinical analysis {>17 years versus <16 years, adjusted odds ratio [OR] 0.910 [95% confidence interval (CI) 0.849–0.975]}. The causal estimates obtained by the inverse variance method in the two-sample MR indicated that higher genetically predicted education attainment causally reduced the risk of CKD [OR 0.934 (95% CI 0.873–0.999)]. Allele score–based MR also supported that higher education attainment was causally linked to a decreased risk of CKD [adjusted OR 0.944 (95% CI 0.922–0.966)].

          Conclusion

          The study suggests that higher education attainment causally reduces the risk of CKD development in the general population.

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          Most cited references24

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            mice: Multivariate Imputation by Chained Equations inR

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              UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

              Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                August 2021
                22 December 2020
                22 December 2020
                : 14
                : 8
                : 1932-1938
                Affiliations
                [1 ] Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul, Korea
                [2 ] Department of Internal Medicine, Armed Forces Capital Hospital , Gyeonggi-do, Korea
                [3 ] Department of Internal Medicine, Seoul National University Hospital , Seoul, Korea
                [4 ] Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Korea
                [5 ] Department of Internal Medicine, Keimyung University School of Medicine , Daegu, Korea
                [6 ] Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital , Seoul, Korea
                [7 ] Kidney Research Institute, Seoul National University , Seoul, Korea
                [8 ] Department of Internal Medicine, Seoul National University Boramae Medical Center , Seoul, Korea
                Author notes
                Correspondence to: Dong Ki Kim; E-mail: dkkim73@ 123456gmail.com
                Author information
                https://orcid.org/0000-0003-0137-5261
                Article
                sfaa240
                10.1093/ckj/sfaa240
                8323131
                34345417
                c23d98fc-0e80-4909-a949-64f06e035bd8
                © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 28 July 2020
                : 8 October 2021
                : 08 October 2020
                Page count
                Pages: 7
                Funding
                Funded by: Seoul National University R&DB Foundation;
                Award ID: 800-20190571
                Categories
                Original Articles
                AcademicSubjects/MED00340

                Nephrology
                chronic kidney disease,education,mendelian randomization,socioeconomic status
                Nephrology
                chronic kidney disease, education, mendelian randomization, socioeconomic status

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