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      Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

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          Abstract

          Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m 2/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT ( vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.

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          Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

          Josef Coresh, P Muntner, J. Smith … (2000)
          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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            Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences.

            N. Vaziri (2006)
            Chronic renal failure (CRF) results in profound lipid disorders, which stem largely from dysregulation of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein metabolism. Specifically, maturation of HDL is impaired and its composition is altered in CRF. In addition, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentrations are elevated in CRF. Impaired maturation of HDL in CRF is primarily due to downregulation of lecithin-cholesterol acyltransferase (LCAT) and, to a lesser extent, increased plasma cholesteryl ester transfer protein (CETP). Triglyceride enrichment of HDL in CRF is primarily due to hepatic lipase deficiency and elevated CETP activity. The CRF-induced hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are primarily due to downregulation of lipoprotein lipase, hepatic lipase, and the very-low-density lipoprotein receptor, as well as, upregulation of hepatic acyl-CoA cholesterol acyltransferase (ACAT). In addition, impaired HDL metabolism contributes to the disturbances of triglyceride-rich lipoprotein metabolism. These abnormalities are compounded by downregulation of apolipoproteins apoA-I, apoA-II, and apoC-II in CRF. Together, these abnormalities may contribute to the risk of arteriosclerotic cardiovascular disease and may adversely affect progression of renal disease and energy metabolism in CRF.
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              Cholesterol and the risk of renal dysfunction in apparently healthy men.

              Gary Curhan, Kathryn Rexrode, Danielle J Glynn … (2003)
              Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as /= 240 mg/dl), HDL ( /= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL /= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.
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                Author and article information

                Contributors
                Emmanuel A. Burdmann: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 4 February 2013
                Volume: 8
                Issue: 2
                Electronic Location Identifier: e55643
                Affiliations
                [1 ]Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
                [2 ]Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
                [3 ]Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
                [4 ]Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
                University of Sao Paulo Medical School, Brazil
                Author notes

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

                Data collection: MCK JJL YWC. Critical revisions: JMC SJH HCC. Conceived and designed the experiments: SCC CCH. Performed the experiments: SCC CCH MCK JJL YWC JMC SJH HCC. Analyzed the data: SCC CCH. Wrote the paper: SCC.

                Article
                Publisher ID: PONE-D-12-26212
                DOI: 10.1371/journal.pone.0055643
                PMC ID: 3563532
                PubMed ID: 23390545
                SO-VID: b2f6ad3f-34ef-4e1c-a6f7-6645ba44b565
                Copyright statement: Copyright @ 2013
                License:

                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
                Date received : 28 August 2012
                Date accepted : 28 December 2012
                Page count
                Pages: 6
                Funding
                The authors have no support or funding to report.
                Categories
                Subject: Research Article
                Subject: Biology
                Subject: Biochemistry
                Subject: Lipids
                Subject: Medicine
                Subject: Clinical Research Design
                Subject: Longitudinal Studies
                Subject: Observational Studies
                Subject: Nephrology
                Subject: Chronic Kidney Disease
                Subject: Developmental Nephrology
                Subject: Dialysis
                Subject: Renal Transplantation
                Subject: Nutrition

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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