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      Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study

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          Abstract

          Glomerular filtration rate (GFR) declines with age by approx. 1 ml/min/m 2 per year beginning in the third decade of life. At 70 years of age > 40 ml/min/m 2 of GFR will be lost. Thus, factors affecting loss of GFR have significant public health implications. Furthermore, the definition of chronic kidney disease based on GFR may not be appropriate for the elderly. We analyzed factors affecting absolute and relative change of eGFR over a 5 year period in 12,381 participants of the Gutenberg Health Study. We estimated GFR at baseline and after 5 years of follow-up by two different equations. Association with the decline of estimated GFR (eGFR) was assessed by multivariable regression analysis. We confirmed a median loss of eGFR per year of approx. 1 ml/min/m 2. Aside from albuminuria systolic blood pressure was most strongly associated with faster decline of eGFR followed by echocardiographic evidence of left ventricular diastolic dysfunction and reduced ejection fraction. White blood cell count showed a moderate association with eGFR loss. Diastolic blood pressure, serum uric acid and serum albumin were associated with slower GFR decline in multivariable analysis. Sensitivity analysis with exclusion of individuals taking diuretics, antihypertensive, antidiabetic, or lipid lowering drugs confirmed these associations.

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          CKD: A Call for an Age-Adapted Definition

          Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m 2 . This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 . Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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            Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate: A Cross-sectional Analysis of Pooled Data

            The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.
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              Molecular mechanisms of renal aging

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                Author and article information

                Contributors
                karl.lackner@unimedizin-mainz.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                13 May 2021
                13 May 2021
                2021
                : 11
                : 10165
                Affiliations
                [1 ]GRID grid.410607.4, Institute of Clinical Chemistry and Laboratory Medicine, , University Medical Center of the Johannes Gutenberg University Mainz, ; Langenbeckstrasse 1, 55131 Mainz, Germany
                [2 ]GRID grid.410607.4, Preventive Cardiology and Preventive Medicine, Center for Cardiology, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [3 ]GRID grid.410607.4, Department of Ophthalmology, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [4 ]GRID grid.410607.4, Department of Psychosomatic Medicine and Psychotherapy, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [5 ]GRID grid.410607.4, Institute of Medical Biostatistics, Epidemiology and Informatics, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [6 ]GRID grid.410607.4, Center for Cardiology - Cardiology I, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [7 ]GRID grid.410607.4, Center for Thrombosis and Hemostasis, , University Medical Center of the Johannes Gutenberg University Mainz, ; Mainz, Germany
                [8 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, DZHK (German Centre for Cardiovascular Research), ; Partner Site RhineMain, Mainz, Germany
                Article
                89442
                10.1038/s41598-021-89442-7
                8119940
                33986324
                5e2f57cf-98e3-4aa4-a721-5e2d19c402e8
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 August 2020
                : 22 April 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004346, Stiftung Rheinland-Pfalz für Innovation;
                Award ID: AZ 961-386261/733
                Funded by: FundRef http://dx.doi.org/10.13039/100008349, Boehringer Ingelheim;
                Funded by: Philips Medical Systems
                Funded by: Universitätsmedizin der Johannes Gutenberg-Universität Mainz (8974)
                Categories
                Article
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                © The Author(s) 2021

                Uncategorized
                nephrology,risk factors
                Uncategorized
                nephrology, risk factors

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