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      Association Between Serum High‐Density Lipoprotein Cholesterol Levels and Progression of Chronic Kidney Disease: Results From the KNOW‐CKD

      research-article
      , MD 1 , 2 , , MD, PhD 4 , , MD 1 , , MD 1 , , MD 1 , , MD 1 , , MD 1 , , MD, PhD 1 , , MD, PhD 1 , , MD, PhD 5 , , MD, PhD 6 , , MD, PhD 7 , , MD, PhD 8 , , MD, PhD 9 , , MD, PhD 1 , 3 , , MD, PhD 1 , , MD, PhD 7 , , MD, PhD 1 , , the KNOW‐CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease) Investigators
      Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
      John Wiley and Sons Inc.
      chronic kidney disease, high‐density lipoprotein, high‐density lipoprotein cholesterol, kidney, kidney disease progression, Lipids and Cholesterol, Nephrology and Kidney

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          Abstract

          Background

          High‐density lipoprotein cholesterol ( HDL‐C) levels are generally decreased in patients with chronic kidney disease ( CKD). However, studies on the relationship between HDL‐C and CKD progression are scarce.

          Methods and Results

          We studied the association between serum HDL‐C levels and the risk of CKD progression in 2168 participants of the KNOWCKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). The primary outcome was the composite of a 50% decline in estimated glomerular filtration rate from baseline or end‐stage renal disease. The secondary outcome was the onset of end‐stage renal disease. During a median follow‐up of 3.1 (interquartile range, 1.6–4.5) years, the primary outcome occurred in 335 patients (15.5%). In a fully adjusted Cox model, the lowest category with HDL‐C of <30 mg/dL (hazard ratio, 2.21; 95% CI, 1.30–3.77) and the highest category with HDL‐C of ≥60 mg/dL (hazard ratio, 2.05; 95% CI, 1.35–3.10) were associated with a significantly higher risk of the composite renal outcome, compared with the reference category with HDL‐C of 50 to 59 mg/dL. This association remained unaltered in a time‐varying Cox analysis. In addition, a fully adjusted cubic spline model with HDL‐C being treated as a continuous variable yielded similar results. Furthermore, consistent findings were obtained in a secondary outcome analysis for the development of end‐stage renal disease.

          Conclusions

          A U‐shaped association was observed between serum HDL‐C levels and adverse renal outcomes in this large cohort of patients with CKD. Our findings suggest that both low and high serum HDL‐C levels may be detrimental to patients with nondialysis CKD.

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          Most cited references33

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          Update on Inflammation in Chronic Kidney Disease

          Background: Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting. Summary: The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials. Key Messages: Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in children).
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            Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

            Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends
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              Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

              The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.
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                Author and article information

                Contributors
                hansh@yuhs.ac
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                12 March 2019
                19 March 2019
                : 8
                : 6 ( doiID: 10.1002/jah3.2019.8.issue-6 )
                : e011162
                Affiliations
                [ 1 ] Department of Internal Medicine College of Medicine Institute of Kidney Disease Research Yonsei University Seoul Korea
                [ 2 ] Division of Integrated Medicine Department of Internal Medicine College of Medicine Yonsei University Seoul Korea
                [ 3 ] Department of Internal Medicine College of Medicine Severance Biomedical Science Institute Brain Korea 21 PLUS Yonsei University Seoul Korea
                [ 4 ] Department of Internal Medicine National Health Insurance Service Medical Center Ilsan Hospital Goyang‐si Gyeonggi‐do Korea
                [ 5 ] Department of Internal Medicine Eulji General Hospital Eulji School of Medicine Seoul Korea
                [ 6 ] Department of Internal Medicine Sungkyunkwan University School of Medicine Kangbuk Samsung Hospital Seoul Korea
                [ 7 ] Department of Internal Medicine Seoul National University Hospital Seoul Korea
                [ 8 ] Department of Internal Medicine Chonnam National University Hospital and Medical School Gwangju Korea
                [ 9 ] Department of Prevention and Management Inha University School of Medicine Incheon Korea
                Author notes
                [*] [* ] Correspondence to: Seung Hyeok Han, MD, PhD, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, 50‐1 Yonsei‐ro, Seodaemun‐gu, Seoul 03722, Korea. E‐mail: hansh@ 123456yuhs.ac
                [†]

                Dr Nam and Dr Chang contributed equally to this work.

                [‡]

                A complete list of the KNOW‐CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease) Investigators is given in Appendix  S1.

                Article
                JAH33947
                10.1161/JAHA.118.011162
                6475054
                30859896
                adf6d989-796a-4584-a070-cb316ca68dcd
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 08 October 2018
                : 11 February 2019
                Page count
                Figures: 5, Tables: 4, Pages: 14, Words: 10398
                Funding
                Funded by: Korea Centers for Disease Control and Prevention
                Award ID: 2011E3300300
                Award ID: 2012E3301100
                Award ID: 2013E3301600
                Award ID: 2013E3301601
                Award ID: 2013E3301602
                Award ID: 2016E3300200
                Categories
                Original Research
                Original Research
                Kidney in Cardiovascular Disease
                Custom metadata
                2.0
                jah33947
                19 March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:19.03.2019

                Cardiovascular Medicine
                chronic kidney disease,high‐density lipoprotein,high‐density lipoprotein cholesterol,kidney,kidney disease progression,lipids and cholesterol,nephrology and kidney

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