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      Relationship of diabetes with renal dysfunction in hypertensive adults

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          Abstract

          We aimed to examine the relationship of diabetes with the estimated glomerular filtration rate (eGFR)-based renal function in the Chinese hypertensive adults.

          This cross-sectional analysis included a total of 18,641 hypertensive adults aged 45 to 75 years. The relationship of diabetes (a fasting glucose ≥7.0 mmol/L or self-reported use of hypoglycemic agents or physician diagnosed diabetes) with glomerular hyperfiltration (an absolute eGFR >90th percentile after adjusting for sex, age), hypofiltration (an eGFR <10th percentile and ≥60 mL/min/1.73 m 2), and reduced eGFR (an eGFR <60 mL/min/1.73 m 2) were estimated by multiple logistic regressions.

          Both the cut-points for hyperfiltration and hypofiltration decreased with age increased, ranging from 115 to 91 mL/min/1.73 m 2 and 91 to 67 mL/min/1.73 m 2, respectively. In the multiple logistic models, diabetes was positively associated with glomerular hyperfiltration (odds ratio [OR]: 2.19, 95% confidence interval [CI]: 1.93–2.47), hypofiltration (1.24, 1.05–1.46), and reduced eGFR (2.88, 2.21–3.76). Furthermore, the stronger association between diabetes and hyperfiltration was found in those with younger age ( P for interaction <.001), or higher total cholesterol (TC) levels ( P for interaction = .008). Consistently, significant association between diabetes and hypofiltration was only observed in participants with younger age ( P for interaction = .043). And detrimentally interaction between diabetes and higher TC levels was also found ( P for interaction <.001) on the risk of reduced eGFR.

          Diabetes was significantly associated with the impairment of renal function, particularly in those with younger age or with higher TC levels. Fasting glucose should be monitored as a marker to identify those with early renal dysfunction.

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          The hyperfiltration theory: a paradigm shift in nephrology.

          Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.
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            Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study.

            Cardiovascular mortality is extremely high in end-stage renal disease. Cardiovascular mortality risk also is increased in selected (high-risk) individuals with mild to moderate impairment of renal function. It is not clear whether a similar association exists in the general population and, if so, through what mechanisms. We investigated the association of renal function with all-cause and cardiovascular mortality in a population-based cohort and explored potential mechanisms underlying any such relationship. An age-, sex-, and glucose-tolerance-stratified sample (N = 631) of a population-based cohort aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow-up, 117 subjects had died (50 of cardiovascular causes). At baseline, renal function was estimated by the serum creatinine level, the Cockcroft-Gault formula and Levey's equation. At baseline, the mean age was 64 +/- 7 years, 48% were men, 55% had hypertension, and 27% (by design) had type 2 diabetes. Serum creatinine was 91.7 +/- 19.0 micromol/L; creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2), and the glomerular filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73 m(2). Renal function was inversely associated with all-cause and with cardiovascular mortality. Relative risks (95% confidence intervals) were 1.08 (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum creatinine; 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5 mL/min/1.73 m(2) creatinine clearance; and 1.15 (1.05 to 1.26) and 1.26 (1.12 to 1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR. These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein. Analyses in diabetic and hypertensive subjects gave similar results. Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality. The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension, diabetes or hyperhomocysteinemia. Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors. Our results were obtained in a general middle-aged to elderly population, and thus have broad applicability.
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              Mortality risk stratification in chronic kidney disease: one size for all ages?

              Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria for chronic kidney disease (CKD) are intended to apply to all age groups. However, it is unclear whether different levels of estimated GFR (eGFR) have the same prognostic significance in older and younger patients. The study cohort was composed of Department of Veterans Affairs (VA) patients who were aged 18 to 100 yr and had at least one outpatient serum creatinine measurement between October 1, 2001, and September 30, 2002 (n=2583,911). Patients with ESRD were excluded. GFR was estimated using the Modification of Diet in Renal Disease equation using each patient's first outpatient creatinine measurement during the study period. The association of eGFR with survival was measured by age group. Twenty percent of cohort patients had an eGFR<60 ml/min per 1.73 m2, ranging from 3% among 18- to 44-yr-olds to as high as 49% among 85- to 100-yr-olds. Fifty-two percent (n=266,421) of cohort patients with an eGFR<60 ml/min per 1.73 m2 had "very" moderate reductions in eGFR into the 50- to 59-ml/min per 1.73 m2 range. The association of eGFR with mortality was weaker in the elderly than in younger age groups: Whereas severe reductions in eGFR were associated with an increased risk for death in all age groups, "very" moderate reductions in eGFR (50 to 59 ml/min per 1.73 m2) were associated with an increased adjusted risk for death only among patients who were younger than 65 yr. Age-related attenuation of the association of eGFR with mortality was also present among women and black patients. In the clinical setting, mortality risk stratification in elderly patients should not be based on the same eGFR cut points as for younger age groups and would benefit from finer categorization of the 30- to 59-ml/min per 1.73 m2 eGFR group.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                June 2017
                16 June 2017
                : 96
                : 24
                : e7169
                Affiliations
                [a ]Department of Emergency, Shenzhen Maternal and Child Healthcare Hospital and The Affiliated Hospital of Southern Medical University
                [b ]National Clinical Research Center of Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou
                [c ]Department of Cardiology, Peking University First Hospital, Beijing, China.
                Author notes
                []Correspondence: Xiping Xu, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (e-mail: xipingxugz@ 123456126.com ).
                Article
                MD-D-16-06706 07169
                10.1097/MD.0000000000007169
                5478339
                28614254
                4bb6afcd-6b34-4cae-95d8-1c9bf7cdc43b
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 7 November 2016
                : 16 May 2017
                : 24 May 2017
                Categories
                4400
                Research Article
                Observational Study
                Custom metadata
                TRUE

                diabetes,fasting glucose,hyperfiltration,hypofiltration,reduced egfr

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