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      Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study

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          Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old.


          To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old.


          Prospective population-based study.


          Municipality of Biella, Piedmont, Italy.


          700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008.


          GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m 2) compared to subjects with eGFR ≥60 mL/min/1.73m 2.


          Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m 2 using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m 2 showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70).


          In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR.

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          Most cited references 29

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          Prediction of creatinine clearance from serum creatinine.

          A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Chronic kidney disease and mortality risk: a systematic review.

            Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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              Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.

              The National Kidney Foundation has advocated the use of the abbreviated Modification of Diet in Renal Disease (MDRD) equation to estimate glomerular filtration rate (GFR) from serum creatinine measurements in clinical laboratories. However, healthy persons were not included in the development of the MDRD equation. To assess the accuracy of the MDRD equation in patients with chronic kidney disease compared with healthy persons and to develop a new equation that uses both patients with chronic kidney disease and healthy persons. Cross-sectional study. The Mayo Clinic, a tertiary-care medical center. Consecutive patients (n = 320) who had an iothalamate clearance test specifically for chronic kidney disease evaluation and consecutive healthy persons (n = 580) who had an iothalamate clearance test specifically for kidney donor evaluation. Serum creatinine levels, GFR, demographic characteristics, and clinical characteristics were abstracted from the medical record. The MDRD equation underestimated GFR by 6.2% in patients with chronic kidney disease and by 29% in healthy persons. Re-estimated coefficients for serum creatinine and sex were similar to the original MDRD equation in the chronic kidney disease series but not in the healthy series. At the same serum creatinine level, age, and sex, GFR was on average 26% higher in healthy persons than in patients with chronic kidney disease (P < 0.001). A quadratic GFR equation was developed to estimate logarithmic GFR from the following covariates: 1/SCr, 1/SCr2, age, and sex (where SCr = serum creatinine). The new equation was not developed in a general population sample. Elderly and African-American persons were underrepresented. The MDRD equation systematically underestimates GFR in healthy persons. A new equation developed with patients who have chronic kidney disease and healthy persons may be a step toward accurately estimating GFR when the diagnosis of chronic kidney disease is unknown.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                28 August 2015
                : 10
                : 8
                [1 ]Laboratory of Geriatric Neuropsychiatry, IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
                [2 ]Laboratory of Analysis, Ospedale degli Infermi, Biella, Italy
                [3 ]County Cancer Registry, Local Health Authority, Biella, Italy
                University Jean MONNET of SAINT-ETIENNE, UNITED STATES
                Author notes

                Competing Interests: The IRCCS-Istituto di Ricerche Farmacologiche Mario Negri received a research grant from Amgen Italia for the "Health and Anemia Study." The authors have declared that they had/have no financial (employment, consultancy, patents, products in development, marketed products, etc.) and non-financial competing interests. The fact that IRFMN received a grant from Amgen does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: SM ER MT UL. Performed the experiments: SM ER MT PD AG UL. Analyzed the data: SM ER MT PD AG UL. Wrote the paper: SM ER MT UL.


                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                Page count
                Figures: 3, Tables: 5, Pages: 16
                The “Health and Anemia Study” was supported by an unrestricted grant from Amgen. The sponsor had no role in the conception and design of the study; collection, management, analysis or interpretation of data; writing of the report; or the decision to submit the article for publication.
                Research Article
                Custom metadata
                Since in the study consent forms signed by the subjects, the possibility that the subjects’ data could be made available upon request by others was not foreseen, we will first need to submit these possible requests for data to the local Ethics Committee for approval. Data are from the "HEALTH AND ANEMIA" study whose author Emma Riva may be contacted at the following mail address: emma.riva@ 123456marionegri.it .



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