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      Variability of the Estimated Glomerular Filtration Rate in the First Year after Kidney Transplantation Is an Independent Risk Factor for Poor Renal Allograft Outcomes: A Retrospective Cohort Study

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          Abstract

          Renal function in the first year after kidney transplantation (KT) can predict long-term renal graft survival. This study investigated whether estimated glomerular filtration rate (eGFR) variability during the first year after KT is a risk factor for poor renal allograft outcomes. This retrospective cohort study included 3077 patients who underwent repeated eGFR measurements for 1 year after KT at Severance Hospital Transplantation Center between 1979 and 2012. The eGFR variability during the first year after KT was the predictor. The patients were divided into four quartile groups of eGFR variability according to the coefficient of variation for eGFR (eGFR-CV). We selected a cutoff of eGFR-CV for graft failure and performed the sensitivity analyses. The graft outcome was worse in the highest quartile group of eGFR variability than in the other groups among all patients (Q4: HR 1.631, 95% CI 1.278–2.081; p < 0.0001) and among patients without AR (Q4: HR 1.425, 95% CI 1.024–1.982; p = 0.0358) after adjusting for eGFR at 1 year after KT and other covariates. Additionally, all-cause mortality was higher in this highest quartile group than in the other groups among all patients but not among patients without AR. Higher eGFR-CVs than the cutoff were significantly associated with a high risk of graft failure among all patients (HR 1.670, 95% CI 1.395–2.000; p < 0.0001) and among patients without AR (HR 1.899, 95% CI 1.457–2.477; p < 0.0001) after fully adjusting for covariates. For all-cause mortality, a higher eGFR-CV was an independent risk factor among all patients but not among patients without AR after adjusting for covariates. eGFR variability in the first year after KT is an independent risk factor for poor renal allograft outcomes.

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          Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.

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            Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

            Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.
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              Long-term survival in renal transplant recipients with graft function.

              Long-term survival in renal transplant recipients with graft function. Death with graft function (DWGF) is a common cause of graft loss. The risks and determinants of DWGF have not been studied in a recent cohort of renal transplant recipients. We performed a population-based survival analysis of U.S. patients with end-stage renal disease (ESRD) transplanted between 1988 and 1997. Registry data were used to evaluate long-term patient survival and cause-specific risks of DWGF in 86,502 adult (>/=18 years) renal transplant recipients. Out of 18,482 deaths, 38% (N = 7040) were deaths with graft function. This accounts for 42. 5% of all graft loss. Patient survival with graft function was 97, 91, and 86% at 1, 5, and 10 years, respectively. The risk of DWGF decreased by 67% (RR = 0.33, P 30%, African American donor race, age> 45 years, and donor death caused by cerebrovascular disease. Patients with graft function have a high long-term survival. Although DWGF is a major cause of graft loss, the risk has declined substantially since 1990. Cardiovascular disease was the predominant reported cause of DWGF. Other causes vary by post-transplant time period. Attention to atherosclerotic risk factors may be the most important challenge to further improve the longevity of patients with successful renal transplants.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 December 2016
                2016
                : 11
                : 12
                : e0168337
                Affiliations
                [1 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [2 ]Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea
                [3 ]The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
                [4 ]Department of Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
                University of Toledo, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: HYC BSK.

                • Data curation: HYC BSK MKS.

                • Formal analysis: MSK HYC BSK.

                • Investigation: HYC BSK.

                • Methodology: HYC BSK MKS.

                • Resources: KHH JGL MSK YSK.

                • Supervision: MSK YSK.

                • Validation: HYC MKS MSK YSK BSK.

                • Visualization: HYC BSK.

                • Writing – original draft: HYC BSK.

                • Writing – review & editing: HYC KHH JGL MSK BSK.

                Article
                PONE-D-16-34712
                10.1371/journal.pone.0168337
                5156409
                27973553
                a3fe1d98-b2e8-420e-b816-ca27b9f59709
                © 2016 Choi et al

                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.

                History
                : 30 August 2016
                : 10 November 2016
                Page count
                Figures: 3, Tables: 4, Pages: 12
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Urinary System Procedures
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Graft Survival
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Regression Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Regression Analysis
                Biology and Life Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Anatomy
                Renal System
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Biology and Life Sciences
                Physiology
                Renal Physiology
                Glomerular Filtration Rate
                Medicine and Health Sciences
                Physiology
                Renal Physiology
                Glomerular Filtration Rate
                Custom metadata
                Data are only available from the Insitutional Data Access for researchers who meet the criteria for access to confidential data. Therefore, our data are available upon request only after permission from the institutional review board of Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, because of ethical and legal restrictions.

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