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Ghimire A, Wanner C, Tonelli M. Closing CKD Treatment Gaps: Why Practice Guidelines and Better Drug Coverage Are Not Enough. Am J Kidney Dis 2025; 85:406-408. [PMID: 39945704 DOI: 10.1053/j.ajkd.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 03/24/2025]
Affiliation(s)
- Anukul Ghimire
- Division of Nephrology, University of Calgary, Calgary, Canada
| | - Christoph Wanner
- Division of Nephrology, University of Würzburg, Würzburg, Germany
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Abidor E, Achkar M, Al Saidi I, Lather T, Jdaidani J, Agarwal A, El-Sayegh S. Comprehensive Review of Lipid Management in Chronic Kidney Disease and Hemodialysis Patients: Conventional Approaches, and Challenges for Cardiovascular Risk Reduction. J Clin Med 2025; 14:643. [PMID: 39860649 PMCID: PMC11765848 DOI: 10.3390/jcm14020643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/12/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Lipid disorders are very prevalent in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), leading to heightened cardiovascular risk. This review examines the effectiveness of lipid-lowering agents in these populations and explores gaps in the current research. The goal of this review is to assess the efficacy of lipid-lowering therapies in CKD and ESRD patients and identify future research needs. It aims to provide a clearer understanding of how these treatments impact cardiovascular risk in high-risk populations. Methods: We conducted a literature search in Embase, PubMed, Cochrane, and Google Scholar databases using keywords including but not limited to: chronic kidney diseases, dialysis, hemodialysis, dyslipidemia, statins, ezetimibe, and lipid-lowering drugs. Findings from included studies were synthetized to provide an overview of the current management of dyslipidemia in ESRD and HD. Results: Statins show mixed results in CKD and ESRD, with limited benefits in reducing cardiovascular events in dialysis patients. Agents like PCSK9 inhibitors show promising results but require further research, while non-statin therapies like fibrates and omega-3 fatty acids have limited evidence for use in this population. Conclusions: The review underscores the need for further research into lipid-lowering agents in CKD and ESRD patients, highlighting the need for tailored lipid management strategies in vulnerable patients with unique risk factors. More studies are needed to refine treatment strategies and assess the role of exercise and accurate risk calculators in managing cardiovascular outcomes.
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Affiliation(s)
- Erica Abidor
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Michel Achkar
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Ibrahim Al Saidi
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Tanvi Lather
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Jennifer Jdaidani
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Alaukika Agarwal
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Suzanne El-Sayegh
- Department of Medicine, Division of Nephrology, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA
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Zhu Y, Lai Y, Hu Y, Fu Y, Zhang Z, Lin N, Huang W, Zheng L. The mechanisms underlying acute myocardial infarction in chronic kidney disease patients undergoing hemodialysis. Biomed Pharmacother 2024; 177:117050. [PMID: 38968794 DOI: 10.1016/j.biopha.2024.117050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/07/2024] Open
Abstract
Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD). Hemodialysis is one of the main treatments for patients with end-stage kidney disease. Epidemiological data has shown that acute myocardial infarction (AMI) accounts for the main reason for death in patients with CKD under hemodialysis therapy. Immune dysfunction and changes in metabolism (including a high level of inflammatory cytokines, a disorder of lipid and mineral ion homeostasis, accumulation of uremic toxins et al.) during CKD can deteriorate stability of atherosclerotic plaque and promote vascular calcification, which are exactly the pathophysiological mechanisms underlying the occurrence of AMI. Meanwhile, the hemodialysis itself also has adverse effects on lipoprotein, the immune system and hemodynamics, which contribute to the high incidence of AMI in these patients. This review aims to summarize the mechanisms and further promising methods of prevention and treatment of AMI in CKD patients undergoing hemodialysis, which can provide an excellent paradigm for exploring the crosstalk between the kidney and cardiovascular system.
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Affiliation(s)
- Yujie Zhu
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China
| | - Yuchen Lai
- School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Yuxuan Hu
- Hubei University of Science and Technology, Xianning 437100, China
| | - Yiwen Fu
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China
| | - Zheng Zhang
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China
| | - Nan Lin
- Department of Cardiology, Fujian Provincial Hospital, Fuzhou 350013, China
| | - Wei Huang
- Department of Cardiology, General Hospital of Central Theater Command, No.627, Wuluo Road, Wuhan 430070, China.
| | - Lemin Zheng
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Beijing Institute of Brain Disorders, The Capital Medical University, Beijing 100050, China.
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4
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Cashmore B, Tunnicliffe DJ, Palmer S, Blythen L, Boag J, Kostner K, Krishnasamy R, Lambert K, Miller A, Mullan J, Patu M, Phoon RKS, Rix L, Trompf N, Johnson DW, Walker R. Australian and New Zealand Living Guideline cholesterol-lowering therapy for people with chronic kidney disease (CARI Guidelines): Reducing the evidence-practice gap. Nephrology (Carlton) 2024; 29:495-509. [PMID: 38684481 DOI: 10.1111/nep.14295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/23/2024] [Accepted: 03/10/2024] [Indexed: 05/02/2024]
Abstract
AIM People with chronic kidney disease experience high rates of cardiovascular disease. Cholesterol-lowering therapy is a mainstay in the management but there is uncertainty in the treatment effects on patient-important outcomes, such as fatigue and rhabdomyolysis. Here, we summarise the updated CARI Australian and New Zealand Living Guidelines on cholesterol-lowering therapy in chronic kidney disease. METHODS We updated a Cochrane review and monitored newly published studies weekly to inform guideline development according to international standards. The Working Group included expertise from nephrology, cardiology, Indigenous Health, guideline development and people with lived experience of chronic kidney disease. RESULTS The guideline recommends people with chronic kidney disease (eGFR ≥15 mL/min/1.73 m2) and an absolute cardiovascular risk of 10% or higher should receive statin therapy (with or without ezetimibe) to reduce the risk of cardiovascular events and death (strong recommendation, moderate certainty evidence). The guidelines also recommends a lower absolute cardiovascular risk threshold (≥5%) for Aboriginal and Torres Strait Islander Peoples and Māori with chronic kidney disease to receive statin therapy (with or without ezetimibe) (strong recommendation, low certainty evidence). The evidence was actively surveyed from 2020-2023 and updated as required. No changes to guideline recommendations were made, with no new data on the balance and benefits of harms. CONCLUSIONS The development of living guidelines was feasible and provided the opportunity to update recommendations to improve clinical decision-making in real-time. Living guidelines provide the opportunity to transform chronic kidney disease guidelines.
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Affiliation(s)
- Brydee Cashmore
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital of Westmead, Sydney, New South Wales, Australia
| | - David J Tunnicliffe
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital of Westmead, Sydney, New South Wales, Australia
| | - Suetonia Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | | | - Jane Boag
- Consumer Partner, Australia
- School of Health, Federation University, Ballarat, Victoria, Australia
| | - Karam Kostner
- Mater Hospital, University of Queensland, St Lucia, Queensland, Australia
| | - Rathika Krishnasamy
- Department of Nephrology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia
- Centre for Kidney Disease Research, The University of Queensland, Brisbane, Queensland, Australia
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland, Australia
| | - Kelly Lambert
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia
| | - Andrea Miller
- Cape York Kidney Care, Weipa Integrated Health Services, Weipa, Queensland, Australia
| | - Judy Mullan
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia
| | - Maira Patu
- Māori/Indigenous Health Institute, University of Otago, Christchurch, New Zealand
| | - Richard K S Phoon
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Department of Renal Medicine, Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
| | - Liz Rix
- Adelaide Nursing School, University of Adelaide, Adelaide, South Australia, Australia
| | | | - David W Johnson
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland, Australia
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
- Translational Research Institute, Brisbane, Queensland, Australia
| | - Robert Walker
- Department of Medicine, University of Otago Dunedin, Dunedin, New Zealand
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5
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Nakata K, Tanaka Y, Harada M, Hitaka M, Joki N. Association between Myocardial Oxygen Supply and Demand and Myocardial Injury in Patients with End-Stage Kidney Disease. J Atheroscler Thromb 2024; 31:540-549. [PMID: 38092391 PMCID: PMC11079495 DOI: 10.5551/jat.64455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/23/2023] [Indexed: 05/03/2024] Open
Abstract
AIM In patients with end-stage kidney disease (ESKD), it is unclear whether an imbalance between myocardial oxygen supply and demand leads to myocardial injury (MI). This study clarifies the association between the balance of the rate pressure product (RPP), consisting of the systolic blood pressure multiplied by the pulse rate (PR), a marker for myocardial oxygen demand, and hemoglobin (Hb), a marker for oxygen supply, with MI. METHODS A total of 283 consecutive unselected patients for hemodialysis were enrolled in this retrospective, cross-sectional study, and were divided into four groups according to Hb levels (high or low) and RPP. Potential imbalances between myocardial oxygen supply and demand were defined as patients with simultaneous high RPP and low Hb levels. The odds ratio (OR) for MI, defined as cardiac troponin T (cTnT) of ≥ 0.15 ng/mL was investigated using logistic regression analysis between the four patient groups. RESULTS The mean age was 68.7 years, 71.3% were men, and 52.6% had diabetes. The mean Hb level was 9.0 g/dL, and 20.5% of patients were latently diagnosed with MI. The median RPP and cTnT level was 12,144 and 0.083 ng/mL, respectively. When exposed to simultaneous high RPP with low Hb, OR significantly increased compared with that of the well-balanced group (RPP ＜12,500 and Hb ≥ 9.0 g/dL; OR 3.63, p＜0.05). Similar results were obtained in multivariate analysis after adjusting for confounding variables. These associations were enhanced or weakened when the Hb cut-off level became lower (Hb=8 g/dL) or higher (Hb=10 g/dL). CONCLUSIONS As the myocardial oxygen supply and demand balance in patients with ESKD is potentially associated with MI, appropriate management for blood pressure, PR, and anemia may prevent MI.
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Affiliation(s)
- Kenji Nakata
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Yuri Tanaka
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Minako Harada
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Mai Hitaka
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Nobuhiko Joki
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
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Zhu D, Judge PK, Haynes R. Improvements in Kidney Outcomes Over the Years: Reason for Optimism but a Challenge for Trialists. Am J Kidney Dis 2024; 83:427-428. [PMID: 38260929 DOI: 10.1053/j.ajkd.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 12/17/2023] [Indexed: 01/24/2024]
Affiliation(s)
- Doreen Zhu
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Parminder K Judge
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Richard Haynes
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
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7
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Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev 2023; 11:CD007784. [PMID: 38018702 PMCID: PMC10685396 DOI: 10.1002/14651858.cd007784.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2023]
Abstract
BACKGROUND Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). OBJECTIVES To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. An updated search will be undertaken every three months. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m2) were included. DATA COLLECTION AND ANALYSIS Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m2. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I2 = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy. AUTHORS' CONCLUSIONS Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Affiliation(s)
- David J Tunnicliffe
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Suetonia C Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Brydee A Cashmore
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Valeria M Saglimbene
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | | | - Kelly Lambert
- School of Medicine, University of Wollongong, Wollongong, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia
- Translational Research Institute, Brisbane, Australia
| | - Jonathan C Craig
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Giovanni Fm Strippoli
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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Fayed A, Mohamed A, Ahmed RM, Abouzeid S, Soliman A. Study of Serum Fibroblast Growth Factor 23 as a Predictor of Endothelial Dysfunction among Egyptian Patients with Diabetic Kidney Disease. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2023; 34:305-312. [PMID: 38345585 DOI: 10.4103/1319-2442.395446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2024] Open
Abstract
Endothelial dysfunction in patients with diabetic nephropathy is caused by nontraditional factors in addition to common risk factors (e.g., hypertension) in people with normal kidney function. These nontraditional factors include factors involved in mineral bone disease in these patients. One of these factors is fibroblast growth factor 23 (FGF-23). We aimed to evaluate the relationship between flow-mediated dilatation (FMD) as a measure of endothelial dysfunction and FGF-23. This was a cross-sectional observational study that was conducted on 100 diabetic patients (Group I: 50 patients with nephropathy; Group II: 50 patients without nephropathy) and 50 healthy volunteers (Group III). Serum levels of intact FGF-23, interleukin-6, intact parathyroid hormone, and 25-hydroxyvitamin D (25-(OH)Vit D); estimated insulin resistance; and FMD were evaluated. FGF-23 was significantly higher in Group I (median: 101 pg/mL) and Group II (median: 101 pg/mL) than in Group III (median: 4 pg/mL) (P <0.001), but FGF-23 was not significantly different between Groups I and II. A significant positive correlation was found between serum levels of FGF-23 and phosphorus in Group I. A significant negative correlation was found between serum levels of FGF-23 and 25-(OH)Vit D in Group II. However, FGF-23 failed to show a significant correlation with FMD in patients with diabetic nephropathy. Our data suggest another factor that rises earlier than FGF-23 in diabetic nephropathy and causes endothelial dysfunction.
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Affiliation(s)
- Ahmed Fayed
- Department of Internal Medicine, Nephrology Unit, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
| | - AbdelAal Mohamed
- Department of Internal Medicine, Nephrology Unit, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Mahmoud Ahmed
- Department of Internal Medicine, Nephrology Unit, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
| | - Sameh Abouzeid
- Department of Nephrology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Ahmed Soliman
- Department of Internal Medicine, Nephrology Unit, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
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9
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Calice-Silva V, Muenz D, Wong MMY, McCullough K, Charytan D, Reichel H, Robinson B, Stengel B, Massy ZA, Pecoits-Filho R. International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations? Lipids Health Dis 2023; 22:67. [PMID: 37231413 PMCID: PMC10210460 DOI: 10.1186/s12944-023-01833-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 05/09/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.
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Affiliation(s)
- Viviane Calice-Silva
- Pro-Kidney Foundation, Joinville, Brazil
- University of Joinville's Region - UNIVILLE, Joinville, Brazil
| | - Daniel Muenz
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, 3989 Research Park Dr, Ann Arbor, MI, 48108, USA
| | - Michelle M Y Wong
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Keith McCullough
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, 3989 Research Park Dr, Ann Arbor, MI, 48108, USA
| | - David Charytan
- Nephrology Division, New York University Grossman School of Medicine, New York, NY, USA
| | - Helmut Reichel
- Nephrological Center Villingen-Schwenningen, Villingen-Schwenningen, Germany
| | - Bruce Robinson
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, 3989 Research Park Dr, Ann Arbor, MI, 48108, USA
| | - Benedicte Stengel
- Université Paris Saclay, Université Versailles Saint-Quentin en Yvelines, Institut National de La Santé Et de La Recherche Médicale (Inserm), Villejuif, France
- Centre de Recherche en Epidémiologie Et Santé Des Populations (CESP), Equipe Epidémiologie Clinique, Villejuif, France
| | - Ziad A Massy
- Université Paris Saclay, Université Versailles Saint-Quentin en Yvelines, Institut National de La Santé Et de La Recherche Médicale (Inserm), Villejuif, France
- Centre de Recherche en Epidémiologie Et Santé Des Populations (CESP), Equipe Epidémiologie Clinique, Villejuif, France
- Department of Nephrology, CHU Ambroise Paré, APHP, Boulogne, France
| | - Roberto Pecoits-Filho
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, 3989 Research Park Dr, Ann Arbor, MI, 48108, USA.
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10
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Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations. J Hum Hypertens 2023; 37:1-19. [PMID: 36138105 PMCID: PMC9831930 DOI: 10.1038/s41371-022-00751-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/09/2022] [Accepted: 08/31/2022] [Indexed: 01/31/2023]
Abstract
Chronic kidney disease (CKD) is a complex condition with a prevalence of 10-15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy.
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11
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Liao G, Wang X, Li Y, Chen X, Huang K, Bai L, Ye Y, Peng Y. Antidyslipidemia Pharmacotherapy in Chronic Kidney Disease: A Systematic Review and Bayesian Network Meta-Analysis. Pharmaceutics 2022; 15:pharmaceutics15010006. [PMID: 36678635 PMCID: PMC9862001 DOI: 10.3390/pharmaceutics15010006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/30/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND AND AIMS The benefits and safety of antidyslipidemia pharmacotherapy in patients with chronic kidney disease were not well defined so the latest evidence was summarized by this work. METHODS This systematic review and Bayesian network meta-analysis (NMA) included searches of PubMed, Embase, and Cochrane Library from inception to 28 February 2022, for randomized controlled trials of any antilipidaemic medications administered to adults with chronic kidney disease [CKD: defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 not undergoing transplantation], using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool to assess the certainty of the evidence. RESULTS 55 trials and 30 works of them were included in our systematic review and NMA, respectively. In comparisons with no antidyslipidemia therapy or placebo, proprotein convertase subtilisin/Kexin type 9 inhibitors plus statin (PS) was the most effective drug regimen for reducing all-cause mortality (OR 0.62, 95% CI [0.40, 0.93]; GRADE: moderate), followed by moderate-high intensity statin (HS, OR 0.76, 95% CI [0.60, 0.93]; I2 = 66.9%; GRADE: moderate). PS, HS, low-moderate statin (LS), ezetimibe plus statin (ES), and fibrates (F) significantly decreased the composite cardiovascular events. The subgroup analysis revealed the null effect of statins on death (OR 0.92, 95% CI [0.81, 1.04]) and composite cardiovascular events (OR 0.94, 95% CI [0.82, 1.07]) in dialysis patients. CONCLUSION In nondialysis CKD patients, statin-based therapies could significantly and safely reduce all-cause death and major composite cardiovascular events despite the presence of arteriosclerotic cardiovascular disease and LDL-c levels. Aggressive medication regimens, PS and HS, appeared to be more effective, especially in patients with established CAD.
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Affiliation(s)
- Guangzhi Liao
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
| | - Xiangpeng Wang
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yiming Li
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
| | - Xuefeng Chen
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
| | - Ke Huang
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Lin Bai
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
| | - Yuyang Ye
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
| | - Yong Peng
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
- Correspondence: ; Tel.: +86-28-85423362; Fax: +86-28-85423169
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12
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de Sá JR, Rangel EB, Canani LH, Bauer AC, Escott GM, Zelmanovitz T, Bertoluci MC, Silveiro SP. The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD. Diabetol Metab Syndr 2022; 14:81. [PMID: 35690830 PMCID: PMC9188192 DOI: 10.1186/s13098-022-00843-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/03/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.
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Affiliation(s)
- João Roberto de Sá
- Endocrinology Division, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil
| | - Erika Bevilaqua Rangel
- Nephrology Division, UNIFESP, São Paulo, Brazil
- Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Luis Henrique Canani
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Andrea Carla Bauer
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Gustavo Monteiro Escott
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Themis Zelmanovitz
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Marcello Casaccia Bertoluci
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Sandra Pinho Silveiro
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil.
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13
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Kim JE, Choi YJ, Oh SW, Kim MG, Jo SK, Cho WY, Ahn SY, Kwon YJ, Ko GJ. The Effect of Statins on Mortality of Patients With Chronic Kidney Disease Based on Data of the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) and Korea National Health Insurance Claims Database. FRONTIERS IN NEPHROLOGY 2022; 1:821585. [PMID: 37674813 PMCID: PMC10479676 DOI: 10.3389/fneph.2021.821585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 12/29/2021] [Indexed: 09/08/2023]
Abstract
The role of statins in chronic kidney disease (CKD) has been extensively evaluated, but it remains controversial in specific population such as dialysis-dependent CKD. This study examined the effect of statins on mortality in CKD patients using two large databases. In data from the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) from two hospitals, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/m2; we compared survival between patients with or without statin treatment. As a sensitivity analysis, the results were validated with the Korea National Health Insurance (KNHI) claims database. In the analysis of CDM datasets, statin users showed significantly lower risks of all-cause and cardiovascular mortality in both hospitals, compared to non-users. Similar results were observed in CKD patients from the KNHI claims database. Lower mortality in the statin group was consistently evident in all subgroup analyses, including patients on dialysis and low-risk young patients. In conclusion, we found that statins were associated with lower mortality in CKD patients, regardless of dialysis status or other risk factors.
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Affiliation(s)
- Ji Eun Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Yun Jin Choi
- Biomedical Research Institute, Korea University Guro Hospital, Seoul, South Korea
| | - Se Won Oh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea
| | - Myung Gyu Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea
| | - Sang Kyung Jo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea
| | - Won Yong Cho
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea
| | - Shin Young Ahn
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Young Joo Kwon
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Gang-Jee Ko
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
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14
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Marini S, Georgakis MK, Anderson CD. Interactions Between Kidney Function and Cerebrovascular Disease: Vessel Pathology That Fires Together Wires Together. Front Neurol 2021; 12:785273. [PMID: 34899586 PMCID: PMC8652045 DOI: 10.3389/fneur.2021.785273] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 10/26/2021] [Indexed: 12/15/2022] Open
Abstract
The kidney and the brain, as high-flow end organs relying on autoregulatory mechanisms, have unique anatomic and physiological hemodynamic properties. Similarly, the two organs share a common pattern of microvascular dysfunction as a result of aging and exposure to vascular risk factors (e.g., hypertension, diabetes and smoking) and therefore progress in parallel into a systemic condition known as small vessel disease (SVD). Many epidemiological studies have shown that even mild renal dysfunction is robustly associated with acute and chronic forms of cerebrovascular disease. Beyond ischemic SVD, kidney impairment increases the risk of acute cerebrovascular events related to different underlying pathologies, notably large artery stroke and intracerebral hemorrhage. Other chronic cerebral manifestations of SVD are variably associated with kidney disease. Observational data have suggested the hypothesis that kidney function influences cerebrovascular disease independently and adjunctively to the effect of known vascular risk factors, which affect both renal and cerebral microvasculature. In addition to confirming this independent association, recent large-scale human genetic studies have contributed to disentangling potentially causal associations from shared genetic predisposition and resolving the uncertainty around the direction of causality between kidney and cerebrovascular disease. Accelerated atherosclerosis, impaired cerebral autoregulation, remodeling of the cerebral vasculature, chronic inflammation and endothelial dysfunction can be proposed to explain the additive mechanisms through which renal dysfunction leads to cerebral SVD and other cerebrovascular events. Genetic epidemiology also can help identify new pathological pathways which wire kidney dysfunction and cerebral vascular pathology together. The need for identifying additional pathological mechanisms underlying kidney and cerebrovascular disease is attested to by the limited effect of current therapeutic options in preventing cerebrovascular disease in patients with kidney impairment.
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Affiliation(s)
- Sandro Marini
- Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston, MA, United States
| | - Marios K Georgakis
- Institute for Stroke and Dementia Research, University Hospital of LMU Munich, Munich, Germany.,McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, United States.,Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States
| | - Christopher D Anderson
- McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, United States.,Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States.,Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States
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15
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Moisi MI, Bungau SG, Vesa CM, Diaconu CC, Behl T, Stoicescu M, Toma MM, Bustea C, Sava C, Popescu MI. Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease. Diagnostics (Basel) 2021; 11:1518. [PMID: 34441451 PMCID: PMC8391570 DOI: 10.3390/diagnostics11081518] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/15/2021] [Accepted: 08/16/2021] [Indexed: 02/06/2023] Open
Abstract
The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation-fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient's survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.
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Affiliation(s)
- Mădălina Ioana Moisi
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.I.M.); (C.B.)
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.I.M.); (C.B.)
| | - Camelia Cristina Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Tapan Behl
- Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India;
| | - Manuela Stoicescu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.S.); (C.S.); (M.I.P.)
| | - Mirela Mărioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Cristiana Bustea
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.I.M.); (C.B.)
| | - Cristian Sava
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.S.); (C.S.); (M.I.P.)
| | - Mircea Ioachim Popescu
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.S.); (C.S.); (M.I.P.)
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16
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Kim JE, Park S, Kim MS, Kang SJ, Lee JW, Kim KS, Kim YC, Kim DK, Joo KW, Kim YS, Park M, Lee H. Statin initiation and all-cause mortality in incident statin-naïve dialysis patients. Atherosclerosis 2021; 337:59-65. [PMID: 34429195 DOI: 10.1016/j.atherosclerosis.2021.08.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 07/21/2021] [Accepted: 08/12/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND AND AIMS Cardiovascular disease is the main cause of death in end-stage kidney disease (ESKD) patients. We aimed to explore the association between statin initiation after starting dialysis and all-cause mortality in statin-naïve ESKD patients. METHODS We analyzed nationwide claims data of incident dialysis patients from 2010 to 2017 in South Korea. Patients who had previous cardiovascular events or were administered statins before dialysis were excluded. The study group included dialysis patients receiving statins within 1 year after dialysis initiation. The control group was organized after propensity-score matching with age, sex, time of dialysis initiation, and underlying diabetes mellitus and hypertension. The main outcomes were all-cause mortality and major cardiovascular events. RESULTS We included 1596 patients who started statin treatment and 1:1 matched statin-nonusers. During the 9438 person-year follow-up, 468 deaths and 264 major adverse cardiovascular events (MACEs) occurred. Statin initiation was associated with a reduced risk of all-cause mortality (adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.60-0.87, p = 0.001), but not with MACE incidence (aHR 1.06, 95% CI 0.83-1.36, p = 0.62). In particular, patients prescribed the recommended dosage of statins according to the Kidney Disease Improving Global Outcomes guidelines showed the lowest mortality risk (aHR 0.55, 95% CI 0.40-0.75, p < 0.001). CONCLUSIONS Statin initiation was associated with lower risk of all-cause mortality in statin-naïve ESKD patients. As indication bias may be present in observational study setting, further prospective studies are warranted to validate the association of statin initiation with mortality in incident dialysis cases.
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Affiliation(s)
- Ji Eun Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Sehoon Park
- Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, South Korea
| | - Myeong-Seok Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Sung Jin Kang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Jang Wook Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Kwang Soo Kim
- Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, South Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Kidney Research Institute, Seoul National University, Seoul, South Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Kidney Research Institute, Seoul National University, Seoul, South Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Kidney Research Institute, Seoul National University, Seoul, South Korea
| | - Minsu Park
- Department of Informations and Statistics, Chungnam National University, Daejeon, South Korea.
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
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17
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Speer T, Ridker PM, von Eckardstein A, Schunk SJ, Fliser D. Lipoproteins in chronic kidney disease: from bench to bedside. Eur Heart J 2021; 42:2170-2185. [PMID: 33393990 DOI: 10.1093/eurheartj/ehaa1050] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/16/2020] [Accepted: 12/08/2020] [Indexed: 12/24/2022] Open
Abstract
Chronic kidney disease (CKD) is associated with high cardiovascular risk. CKD patients exhibit a specific lipoprotein pattern termed 'uraemic dyslipidaemia', which is characterized by rather normal low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride plasma levels. All three lipoprotein classes are involved in the pathogenesis of CKD-associated cardiovascular diseases (CVDs). Uraemia leads to several modifications of the structure of lipoproteins such as changes of the proteome and the lipidome, post-translational protein modifications (e.g. carbamylation) and accumulation of small-molecular substances within the lipoprotein moieties, which affect their functionality. Lipoproteins from CKD patients interfere with lipid transport and promote inflammation, oxidative stress, endothelial dysfunction as well as other features of atherogenesis, thus contributing to the development of CKD-associated CVD. While, lipid-modifying therapies play an important role in the management of CKD patients, their efficacy is modulated by kidney function. Novel therapeutic agents to prevent the adverse remodelling of lipoproteins in CKD and to improve their functional properties are highly desirable and partially under development.
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Affiliation(s)
- Thimoteus Speer
- Translational Cardio-Renal Medicine, Saarland University, Kirrberger Strasse, Building 41, D-66421 Homburg/Saar, Germany.,Department of Internal Medicine IV, Saarland University Hospital, Nephrology and Hypertension, Kirrberger Strasse, Building 41, D-66421 Homburg/Saar, Germany
| | - Paul M Ridker
- Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA
| | - Arnold von Eckardstein
- Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland
| | - Stefan J Schunk
- Translational Cardio-Renal Medicine, Saarland University, Kirrberger Strasse, Building 41, D-66421 Homburg/Saar, Germany
| | - Danilo Fliser
- Translational Cardio-Renal Medicine, Saarland University, Kirrberger Strasse, Building 41, D-66421 Homburg/Saar, Germany
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18
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Mathew RO, Rosenson RS, Lyubarova R, Chaudhry R, Costa SP, Bangalore S, Sidhu MS. Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease. Cardiovasc Drugs Ther 2021; 35:479-489. [PMID: 32556851 DOI: 10.1007/s10557-020-07020-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.
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Affiliation(s)
- Roy O Mathew
- Columbia V.A. Health Care System, 6439 Garners Ferry Road, Columbia, SC, 29209, USA.
- University of South Carolina School of Medicine, Columbia, SC, USA.
| | | | | | | | | | | | - Mandeep S Sidhu
- Albany Medical College and Albany Medical Center, Albany, NY, USA
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19
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Lau WL. Controversies: Stroke Prevention in Chronic Kidney Disease. J Stroke Cerebrovasc Dis 2021; 30:105679. [PMID: 33640261 DOI: 10.1016/j.jstrokecerebrovasdis.2021.105679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 02/04/2021] [Accepted: 02/10/2021] [Indexed: 11/17/2022] Open
Abstract
Risk of both ischemic and hemorrhagic stroke is increased in the chronic kidney disease (CKD) population, particularly in end-stage kidney disease patients. Uremic factors that contribute to stroke risk include blood pressure variability, vascular calcification, build-up of vascular toxins, chronic inflammation, platelet dysfunction and increased brain microbleeds. This paper discusses the controversial evidence for stroke prevention strategies including blood pressure control, statins, antiplatelet agents, and anticoagulation in the CKD population. Only a few randomized clinical trials included patients with advanced CKD, thus evidence is derived mostly from observational cohorts and real-world data. Overall, targeting a lower systolic blood pressure below 120 mmHg and statin prescription do not appear to decrease stroke risk in CKD. Antiplatelet agents have not shown a clear benefit for secondary stroke prevention, but aspirin may reduce incident stroke in hypertensive CKD stage 3B-5 patients. Observational data suggests that the factor Xa inhibitor apixaban has a favorable profile over warfarin in dialysis patients with atrial fibrillation; apixaban being associated with lower stroke risk and fewer major bleeding events.
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Affiliation(s)
- Wei Ling Lau
- Division of Nephrology and Hypertension, University of California Irvine, Irvine, 333 City Blvd West, Suite 400, Orange, CA, USA.
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20
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Relationship between serum lipid concentrations and impaired renal function in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry Study. Clin Exp Nephrol 2021; 25:385-393. [PMID: 33398604 DOI: 10.1007/s10157-020-02000-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 11/20/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND Patients with chronic kidney disease (CKD) have a higher risk of atherosclerotic cardiovascular disease (ASCVD). Dyslipidemia has been established as a risk factor for ASCVD. In the present study, we aimed to determine the prevalence of dyslipidemia at each stage of CKD. METHODS We conducted a cross-sectional study among 4476 patients registered in the Fukuoka Kidney Disease Registry Study, a Japanese prospective cohort study in patients with non-dialysis-dependent CKD. Outcomes were the prevalence of hyper-low-density lipoprotein (LDL) cholesterolemia, hyper-non-high-density lipoprotein (non-HDL) cholesterolemia, hypertriglyceridemia, and hypo-high-density lipoprotein (hypo-HDL) cholesterolemia at each stage of CKD. We analyzed the relationships between CKD stage and the prevalence of dyslipidemia using logistic regression models. RESULTS Patients in the advanced stages of CKD were more likely to have hypertriglyceridemia [OR 2.16 (95% CI 1.03-4.56), OR 2.24 (95% CI 1.04-4.84), OR 2.62 (95% CI 1.19-5.78), and OR 2.47 (95% CI 1.04-5.88) for CKD stages G3a, G3b, G4, and G5, respectively] and hypo-HDL-cholesterolemia [OR 2.66 (95% CI 1.21-5.82), OR 3.10 (95% CI 1.38-6.95), OR 2.86 (95% CI 1.25-6.53), and OR 3.30 (95% CI 1.35-8.10) for CKD stages G3a, G3b, G4, and G5, respectively] as compared with patients in CKD stage G1. The prevalence of hyper-LDL-cholesterolemia and hyper-non-HDL-cholesterolemia was not related to CKD stage. CONCLUSION Patients with advanced CKD stages are more likely to have hypertriglyceridemia and hypo-HDL-cholesterolemia than those in early stages. This type of lipid profile may represent a risk factor for ASCVD in patients with CKD.
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21
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Abstract
: Chronic kidney disease (CKD) is a public health threat with impact in cardiovascular risk. All forms of cardiovascular disease and mortality are more common in CKD. Treatment of cardiovascular risk factors, hypertension, dyslipidemia and diabetes is essential for cardiovascular and kidney protection. CKD is a marker of high or very high cardiovascular risk and its presence require early treatment and specific goals. Lifestyle is a pivotal factor, stopping smoking, reducing weight in the overweight or obese, starting regular physical exercise and healthy dietary pattern are recommended. Office BP should be lowered towards 130/80 mmHg or even lower if tolerated with sodium restriction and single pill combination, including angiotensin system blocker. Out-of-office BP monitoring, mainly 24-h assessment, is recommended. Diabetes requires treatment from the moment of diagnosis, but prediabetes benefits with lifestyle changes and metformin in patients stage 2 and 3a. iSGLT2 and GLP-1RA are initially recommended in T2D patients with high or very high cardiovascular risk. Concerning dyslipidemia, for patients in stage 4, LDL-C 55 mg/dl or less (1.4 mmol/l) and an LDL-C reduction of 50% or less from baseline is recommended. In stage 3, LDL-C goal is 70 mg/dl or less (1.8 mmol/l) and an LDL-C. reduction of at least 50% from baseline. Statins are the lipid-lowering therapy of choice with or without ezetimibe. Higher doses of statins are required as GFR declines. Available evidence suggests that combined PCSK9 inhibitors with maximally tolerated dose of statins may have an emerging role in treatment of dyslipidemia in CKD patients.
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22
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Huang X, Jia Y, Zhu X, Zhang Y, Jiang L, Wei X, Zhao D, Zhao X, Du Y. Effects of Statins on Lipid Profile of Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials. BIOMED RESEARCH INTERNATIONAL 2020; 2020:9094543. [PMID: 32462035 PMCID: PMC7212277 DOI: 10.1155/2020/9094543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 03/21/2020] [Accepted: 04/07/2020] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To assess the benefits of statins on lipid profile in kidney transplant recipients via a meta-analysis. METHODS We systematically identified peer-reviewed clinical trials, review articles, and treatment guidelines from PubMed, Embase, the Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), SinoMed (CBM), and Chongqing VIP databases from inception to April 2019. In the analysis, only randomized controlled clinical trials performed in human were included. RESULTS Eight articles were included in the analysis, involving 335 kidney transplant recipients who received statins and 350 kidney transplant patients as the control group. Results revealed that statins improved the lipid profile of kidney transplant recipients. Specifically, statin therapy significantly reduced total cholesterol and low-density lipoprotein cholesterol. However, it had no effects on high-density lipoprotein cholesterol and triglyceride levels. CONCLUSIONS The present study provides valuable knowledge on the potential benefits of statins in kidney transplant recipients. This meta-analysis shows that statin therapy modifies the lipid profile in this patient population.
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Affiliation(s)
- Xiu Huang
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Yong Jia
- School of Nursing, Jilin University, Changchun 130000, China
| | - Xiaoyu Zhu
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Yangyang Zhang
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Lili Jiang
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Xuejiao Wei
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Dan Zhao
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Xiaoxia Zhao
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
| | - Yujun Du
- Department of Nephrology, The First Hospital of Jilin University, Changchun 130000, China
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23
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Law JP, Price AM, Pickup L, Radhakrishnan A, Weston C, Jones AM, McGettrick HM, Chua W, Steeds RP, Fabritz L, Kirchhof P, Pavlovic D, Townend JN, Ferro CJ. Clinical Potential of Targeting Fibroblast Growth Factor-23 and αKlotho in the Treatment of Uremic Cardiomyopathy. J Am Heart Assoc 2020; 9:e016041. [PMID: 32212912 PMCID: PMC7428638 DOI: 10.1161/jaha.120.016041] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease.
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Affiliation(s)
- Jonathan P. Law
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Anna M. Price
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Luke Pickup
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Ashwin Radhakrishnan
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
| | - Chris Weston
- Institute of Immunology and ImmunotherapyUniversity of BirminghamUnited Kingdom
- NIHR Birmingham Biomedical Research CentreUniversity Hospitals Birmingham NHS Foundation Trust and University of BirminghamUnited Kingdom
| | - Alan M. Jones
- School of PharmacyUniversity of BirminghamUnited Kingdom
| | | | - Winnie Chua
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Richard P. Steeds
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Larissa Fabritz
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Paulus Kirchhof
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Davor Pavlovic
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Jonathan N. Townend
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Charles J. Ferro
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
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Abstract
Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; “remnant particles”), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition–inflammation.Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (≤ 20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30% – 50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD (“4D”); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.
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Affiliation(s)
- Sabin Shurraw
- Division of Nephrology University of Alberta, Canada
| | - Marcello Tonelli
- Division of Nephrology University of Alberta, Canada
- Division of Critical Care Medicine, University of Alberta, Canada
- Institute of Health Economics, Edmonton, Alberta, Canada
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25
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Heimbürger O, Stenvinkel P. Statins to Treat Chronic Inflammation in Dialysis Patients — is this Feasible? Perit Dial Int 2020. [DOI: 10.1177/089686080702700308] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Olof Heimbürger
- Department of Renal Medicine Karolinska University Hospital Division of Renal Medicine Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm, Sweden
| | - Peter Stenvinkel
- Department of Renal Medicine Karolinska University Hospital Division of Renal Medicine Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm, Sweden
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Pontremoli R, Bellizzi V, Bianchi S, Bigazzi R, Cernaro V, Del Vecchio L, De Nicola L, Leoncini G, Mallamaci F, Zoccali C, Buemi M. Management of dyslipidaemia in patients with chronic kidney disease: a position paper endorsed by the Italian Society of Nephrology. J Nephrol 2020; 33:417-430. [PMID: 32065354 PMCID: PMC7220980 DOI: 10.1007/s40620-020-00707-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 01/24/2020] [Indexed: 12/19/2022]
Abstract
Chronic kidney disease (CKD) represents a major public health issue worldwide and entails a high burden of cardiovascular events and mortality. Dyslipidaemia is common in patients with CKD and it is characterized by a highly atherogenic profile with relatively low levels of HDL-cholesterol and high levels of triglyceride and oxidized LDL-cholesterol. Overall, current literature indicates that lowering LDL-cholesterol is beneficial for preventing major atherosclerotic events in patients with CKD and in kidney transplant recipients while the evidence is less clear in patients on dialysis. Lipid lowering treatment is recommended in all patients with stage 3 CKD or worse, independently of baseline LDL-cholesterol levels. Statin and ezetimibe are the cornerstones in the management of dyslipidaemia in patients with CKD, however alternative and emerging lipid-lowering therapies may acquire a central role in near future. This position paper endorsed by the Italian Society of Nephrology aims at providing useful information on the topic of dyslipidaemia in CKD and at assisting decision making in the management of these patients.
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Affiliation(s)
- Roberto Pontremoli
- Università degli Studi and I.R.C.C.S. Ospedale Policlinico San Martino, Viale Benedetto XV 6, 16132, Genoa, Italy.
| | - Vincenzo Bellizzi
- Division of Nephrology, Dialysis and Transplantation, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Via San Leonardo, 84131, Salerno, Italy
| | - Stefano Bianchi
- Nephrology and Dialysis Complex Operative Unit, Department of Internal Medicine, ASL Toscana Nordovest, Livorno, Italy
| | - Roberto Bigazzi
- Nephrology and Dialysis Complex Operative Unit, Department of Internal Medicine, ASL Toscana Nordovest, Livorno, Italy
| | - Valeria Cernaro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy
| | - Lucia Del Vecchio
- Department of Nephrology and Dialysis, A. Manzoni Hospital, ASST Lecco, Lecco, Italy
| | - Luca De Nicola
- Nephrology Division, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Giovanna Leoncini
- Università degli Studi and I.R.C.C.S. Ospedale Policlinico San Martino, Viale Benedetto XV 6, 16132, Genoa, Italy
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy.,CNR-IFC, Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Nefrologia-Ospedali Riuniti, 89100, Reggio Calabria, Italy
| | - Carmine Zoccali
- Nephrology, Dialysis and Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy
| | - Michele Buemi
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy
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27
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Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell PB, Brinton EA, Pollak A, Braun LT, Welty FK. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol 2019; 39:e38-e81. [PMID: 30580575 DOI: 10.1161/atv.0000000000000073] [Citation(s) in RCA: 449] [Impact Index Per Article: 74.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.
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Abstract
An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations.
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29
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Herrera-Gómez F, Chimeno MM, Martín-García D, Lizaraso-Soto F, Maurtua-Briseño-Meiggs Á, Grande-Villoria J, Bustamante-Munguira J, Alamartine E, Vilardell M, Ochoa-Sangrador C, Álvarez FJ. Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses. Sci Rep 2019; 9:8951. [PMID: 31222137 PMCID: PMC6586647 DOI: 10.1038/s41598-019-45431-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 06/05/2019] [Indexed: 12/11/2022] Open
Abstract
Pairwise and network meta-analyses on the relationship between the efficacy of the use of statins with or without ezetimibe and reductions in low-density lipoprotein cholesterol (LDLc) and C-reactive protein (CRP) in patients with chronic kidney disease (CKD) are presented. In the pairwise meta-analysis, statins with or without ezetimibe were shown to be efficacious in reducing major adverse cardiovascular events (MACE) in patients with CKD and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, in the context of both primary prevention [odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.50/0.40–0.64/0%/6] and primary/secondary prevention (0.66/0.57–0.76/57%/18). However, in the Bayesian network meta-analysis, compared to the placebo, only atorvastatin 80 mg daily and atorvastatin and rosuvastatin at doses equivalent to simvastatin 20 mg daily reduced the odds of MACEs in this patient population. The network meta-analysis for LDLc and CRP treatment objectives also showed that, regardless of eGFR and excluding dialysis patients, the number of MACEs decreased in patients with CKD, with reductions in both LDLc and CRP of less than 50% (surface under the cumulative ranking (SUCRA)/heterogeneity (vague)/n: 0.77/0.14/3). The evaluation of the benefits of drugs may lead to individualized therapy for CKD patients: Cholesterol-lowering treatment for CKD patients with high levels of both LDLc and CRP is suggested.
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Affiliation(s)
- Francisco Herrera-Gómez
- Pharmacological Big Data Laboratory, Pharmacology and Therapeutics, Faculty of Medicine, University of Valladolid, Valladolid, Spain. .,Nephrology, Hospital Virgen de la Concha - Sanidad de Castilla y León, Zamora, Spain.
| | - M Montserrat Chimeno
- Internal Medicine, Hospital Virgen de la Concha - Sanidad de Castilla y León, Zamora, Spain
| | - Débora Martín-García
- Cardiovascular risk unit, Hospital Clínico Universitario de Valladolid - Sanidad de Castilla y León, Valladolid, Spain
| | - Frank Lizaraso-Soto
- Instituto de Investigación de la Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Peru
| | | | - Jesús Grande-Villoria
- Nephrology, Hospital Virgen de la Concha - Sanidad de Castilla y León, Zamora, Spain
| | - Juan Bustamante-Munguira
- Cardiac Surgery, Hospital Clínico Universitario de Valladolid - Sanidad de Castilla y León, Valladolid, Spain
| | - Eric Alamartine
- Nephrology, Dialysis and Transplantation, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Priest-en-Jarez, France
| | - Miquel Vilardell
- Medicine, Faculty of Medicine, Universidad Autónoma de Barcelona, Barcelona, Spain
| | | | - F Javier Álvarez
- Pharmacological Big Data Laboratory, Pharmacology and Therapeutics, Faculty of Medicine, University of Valladolid, Valladolid, Spain.,CEIm Área de Salud Valladolid Este, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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30
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Charytan DM, Sabatine MS, Pedersen TR, Im K, Park JG, Pineda AL, Wasserman SM, Deedwania P, Olsson AG, Sever PS, Keech AC, Giugliano RP. Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial. J Am Coll Cardiol 2019; 73:2961-2970. [DOI: 10.1016/j.jacc.2019.03.513] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 03/10/2019] [Accepted: 03/19/2019] [Indexed: 10/26/2022]
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31
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Natanzon SS, Matetzky S, Beigel R, Iakobishvili Z, Goldenberg I, Shechter M. Statin therapy among chronic kidney disease patients presenting with acute coronary syndrome. Atherosclerosis 2019; 286:14-19. [PMID: 31082760 DOI: 10.1016/j.atherosclerosis.2019.05.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 04/04/2019] [Accepted: 05/03/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND AND AIMS The beneficial effect of statin therapy has been well established for both primary and secondary prevention of cardiovascular disease. Nevertheless, it remains under-used among patients with chronic kidney disease (CKD). We aimed to investigate the impact of statin therapy across a wide spectrum of CKD patients presenting with acute coronary syndrome (ACS). METHODS We included all patients with ACS enrolled in the Acute Coronary Syndrome Israel Survey (ACSIS) between the years 2006 and 2016, and allocated them to 3 groups according to their renal function based on an estimated glomerular filtration rate (eGFR) calculation on admission (MDRD formula): eGFR<30 ml/min/1.73 m2 (n = 525, 6%), eGFR 30-59 ml/min/1.73 m2 (n = 1919, 21%), and eGFR>60 ml/min/1.73 m2 (n = 6501, 73%). Primary outcome included in-hospital, 30-day, and 1-year major adverse cardiovascular events (MACE), and the independent prognostic effect of statins among CKD patients with ACS, by Cox regression analysis. RESULTS All 8945 consecutive ACS patients were included in our analysis. On hospital discharge, statin prescriptions were negatively associated with eGFR ]eGFR>60 ml/min/1.73 m2 -95%, eGFR 30-59 ml/min/1.73 m2 -90%, eGFR<30 ml/min/1.73 m2 -78% (p < 0.001 for trend). Kaplan-Meier curves demonstrated both short and long-term higher mortality rates in those prescribed compared with those not prescribed statins (p < 0.001), regardless of renal function. Cox regression analysis revealed the protective effect of discharge statins (HR-0.25, 95% C.I 0.2-0.3, p < 0.001). CONCLUSIONS In our study, the beneficial effect of statins was maintained among CKD patients presenting with ACS. Therefore, these patients should be treated with statins regardless of their eGFR.
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Affiliation(s)
- Sharon Shalom Natanzon
- Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
| | - Shlomi Matetzky
- Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Roy Beigel
- Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Zaza Iakobishvili
- Sackler Faculty of Medicine, Tel Aviv University, Israel; Cardiology Department, Rabin Medical CenterTel Aviv University, Israel
| | - Ilan Goldenberg
- Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Michael Shechter
- Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
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Aitbaev KA, Murkamilov IT, Fomin VV. Hypolipidemic Therapy and Chronic Kidney Disease: Effects on Cardiovascular Risks and Renal Dysfunction. ACTA ACUST UNITED AC 2019; 59:79-87. [PMID: 30853024 DOI: 10.18087/cardio.2019.2.10231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 03/08/2019] [Indexed: 11/18/2022]
Abstract
Steady increase in the prevalence of chronic kidney disease (CKD) is a serious public health problem, since CKD potentially leads to the development of end-stage renal disease (ESRD) that requires high-cost replacement therapy and is closely associated with increased risk of developing cardiovascular diseases (CVD), which are the cause of death in most patients. Progression of renal dysfunction and development of CVD are significantly affected by hyper- and dyslipidemia. This review contains results of studies evaluating the effect of hypolipidemic therapy on reduction of cardiovascular risk and slowdown of renal dysfunction in patients with CKD at pre-dialysis and dialysis stages of renal failure, as well as in patients with kidney transplant. In addition, recommendations on nutrition and new therapeutic approaches to lipid-lowering therapy in patients with CKD, as well as prospects for the usage of new hypolipidemic drugs are also presented.
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Affiliation(s)
- K A Aitbaev
- Research Institute of Molecular Biology and Medicine at the National Center of Cardiology and Therapy Named After acad. M. Mirrakhimov..
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Del Vecchio L, Baragetti I, Locatelli F. New agents to reduce cholesterol levels: implications for nephrologists. Nephrol Dial Transplant 2019; 35:213-218. [DOI: 10.1093/ndt/gfz013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 12/28/2018] [Indexed: 12/20/2022] Open
Affiliation(s)
- Lucia Del Vecchio
- Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, ASST-Lecco, Italy
| | - Ivano Baragetti
- Department of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano—Cinisello Balsamo, Milan, Italy
| | - Francesco Locatelli
- Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, ASST-Lecco, Italy
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Obialo CI, Ofili EO, Norris KC. Statins and Cardiovascular Disease Outcomes in Chronic Kidney Disease: Reaffirmation vs. Repudiation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:E2733. [PMID: 30518032 PMCID: PMC6313800 DOI: 10.3390/ijerph15122733] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 11/28/2018] [Accepted: 11/30/2018] [Indexed: 12/11/2022]
Abstract
Cardiovascular disease (CVD) burden is several-fold higher in patients with chronic kidney disease (CKD). Although statins have been shown to provide significant CVD benefits in both the general population and patients with CKD, this has not translated into survival advantage in patients with advanced CKD or on dialysis. It has been reported that CVD risk continues to escalate as CKD progresses to end-stage kidney disease (ESKD); however, the CVD risk reduction by statins appears to decline as patients' progress from the early to later stages of CKD. Statins have also been associated with a higher incidence of stroke in ESKD patients. Thus, the CVD benefits of statins in ESKD remain questionable.
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Affiliation(s)
- Chamberlain I Obialo
- Department of Medicine, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
| | - Elizabeth O Ofili
- Department of Medicine, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
| | - Keith C Norris
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
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Edmonston D, Morris JD, Middleton JP. Working Toward an Improved Understanding of Chronic Cardiorenal Syndrome Type 4. Adv Chronic Kidney Dis 2018; 25:454-467. [PMID: 30309463 DOI: 10.1053/j.ackd.2018.08.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 08/09/2018] [Accepted: 08/15/2018] [Indexed: 12/17/2022]
Abstract
Chronic diseases of the heart and of the kidneys commonly coexist in individuals. Certainly combined and persistent heart and kidney failure can arise from a common pathologic insult, for example, as a consequence of poorly controlled hypertension or of severe diffuse arterial disease. However, strong evidence is emerging to suggest that cross talk exists between the heart and the kidney. Independent processes are set in motion when kidney function is chronically diminished, and these processes can have distinct adverse effects on the heart. The complex chronic heart condition that results from chronic kidney disease (CKD) has been termed cardiorenal syndrome type 4. This review will include an updated description of the cardiac morphology in patients who have CKD, an overview of the most likely CKD-sourced culprits for these cardiac changes, and the potential therapeutic strategies to limit cardiac complications in patients who have CKD.
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Vanholder R, Van Laecke S, Glorieux G, Verbeke F, Castillo-Rodriguez E, Ortiz A. Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD). Toxins (Basel) 2018; 10:E237. [PMID: 29895722 PMCID: PMC6024824 DOI: 10.3390/toxins10060237] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 05/11/2018] [Indexed: 02/07/2023] Open
Abstract
The uremic syndrome, which is the clinical expression of chronic kidney disease (CKD), is a complex amalgam of accelerated aging and organ dysfunctions, whereby cardio-vascular disease plays a capital role. In this narrative review, we offer a summary of the current conservative (medical) treatment options for cardio-vascular and overall morbidity and mortality risk in CKD. Since the progression of CKD is also associated with a higher cardio-vascular risk, we summarize the interventions that may prevent the progression of CKD as well. We pay attention to established therapies, as well as to novel promising options. Approaches that have been considered are not limited to pharmacological approaches but take into account lifestyle measures and diet as well. We took as many randomized controlled hard endpoint outcome trials as possible into account, although observational studies and post hoc analyses were included where appropriate. We also considered health economic aspects. Based on this information, we constructed comprehensive tables summarizing the available therapeutic options and the number and kind of studies (controlled or not, contradictory outcomes or not) with regard to each approach. Our review underscores the scarcity of well-designed large controlled trials in CKD. Nevertheless, based on the controlled and observational data, a therapeutic algorithm can be developed for this complex and multifactorial condition. It is likely that interventions should be aimed at targeting several modifiable factors simultaneously.
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Affiliation(s)
- Raymond Vanholder
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
| | - Steven Van Laecke
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
| | - Griet Glorieux
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
| | - Francis Verbeke
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
| | | | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain.
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Shen H, Chen X, Lu J, Yang H, Xu Y, Zhu A, Zhang X, Ye F, Gu Y. Effects of statin therapy on chronic kidney disease patients with coronary artery disease. Lipids Health Dis 2018; 17:84. [PMID: 29665812 PMCID: PMC5902851 DOI: 10.1186/s12944-018-0742-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 04/09/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Long-term persistence of statin therapy provided an ongoing reduction in mortality among patients with and without a known history of CVD, and renoprotective effect on CKD patients. Until now, very few reports are available from China to address the effects of statin therapy in CKD + CAD patients. METHODS We compared the effects of long-term statin therapy (follow-up time 4 years) in terms of cardiovascular events, all-cause death, and cardiac death among 254 CKD patients with or without CAD. RESULTS Long-term statin therapy was much more effective in the CKD + CAD patients compared with CKD patients. In the CAD + CKD patients, long-term statins showed a 22.2% reduction in the CVs rate (P = 0.012). With regard to the all-cause and cardiac deaths, long-term statins had significant treatment effects on the CAD + CKD patients (reduction of about 28.1% in mortality rates, P < 0.001). In contrast, long-term statin therapy exerted no significant influence on the clinical outcomes of the CKD-only patients. CONCLUSION Long-term statin therapy more dramatically reduced the CVs and mortality rates of the CKD patients with concomitant CAD. In contrast, CKD-only patients had a good prognosis and did not appear to require statin treatment.
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Affiliation(s)
- Hao Shen
- Department of Clinical Laboratory Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Xiaodong Chen
- Department of Internal Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Jingfen Lu
- Department of Clinical Laboratory Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Honglin Yang
- Department of Clinical Laboratory Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Yan Xu
- Department of Nephrology, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Ao Zhu
- Department of Clinical Laboratory Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Xiao Zhang
- Department of Clinical Laboratory Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Fulong Ye
- Department of Internal Medicine, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
| | - Yongchun Gu
- Department of Central Laboratory, First People’s Hospital of Wujiang District, Nantong University, Suzhou, China
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Changsirikulchai S, Sangthawan P, Janma J, Sripaiboonkij N, Rattanamongkolgul S, Thinkhamrop B. National survey: Evaluation of cardiovascular risk factors in Thai patients with type 2 diabetes and chronic kidney disease after the development of cardiovascular disease. Nephrology (Carlton) 2017; 23:53-59. [DOI: 10.1111/nep.12922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 09/06/2016] [Accepted: 09/07/2016] [Indexed: 01/04/2023]
Affiliation(s)
- Siribha Changsirikulchai
- Renal Division, Department of Medicine, Faculty of Medicine; Srinakharinwirot University; Thailand
| | - Pornpen Sangthawan
- Renal Division, Department of Medicine, Faculty of Medicine; Prince of Songkla University; Thailand
| | - Jirayut Janma
- Renal Division, Department of Medicine, Faculty of Medicine; Srinakharinwirot University; Thailand
| | - Nintita Sripaiboonkij
- Ramathibodi Comprehensive Cancer Center, Faculty of Medicine; Ramathibodi Hospital; Thailand
| | - Suthee Rattanamongkolgul
- Department of Preventive and Social Medicine, Faculty of Medicine; Srinakharinwirot University; Thailand
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Stanifer JW, Charytan DM, White J, Lokhnygina Y, Cannon CP, Roe MT, Blazing MA. Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function. J Am Soc Nephrol 2017; 28:3034-3043. [PMID: 28507057 PMCID: PMC5619955 DOI: 10.1681/asn.2016090957] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 04/10/2017] [Indexed: 12/23/2022] Open
Abstract
Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
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Affiliation(s)
- John W Stanifer
- Division of Nephrology, Department of Medicine,
- Duke Clinical Research Institute, and
| | - David M Charytan
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and
- The Baim Institute, Boston, Massachusetts
| | | | | | - Christopher P Cannon
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and
- The Baim Institute, Boston, Massachusetts
| | - Matthew T Roe
- Duke Clinical Research Institute, and
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina
| | - Michael A Blazing
- Duke Clinical Research Institute, and
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina
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Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis. PLoS One 2017; 12:e0183059. [PMID: 28806769 PMCID: PMC5555708 DOI: 10.1371/journal.pone.0183059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 07/29/2017] [Indexed: 12/02/2022] Open
Abstract
Objective Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. Methods This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. Results In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962–0.996, p = 0.018). Conclusions Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.
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Abstract
BACKGROUND Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted. AIM To determine the extent to which the effectiveness of statins varies by kidney class. DESIGN Meta-analysis. METHODS We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30-59 ml/min), CKD4 (eGFR 15-29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists' Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM). RESULTS A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67-0.78) and ACM (0.82, 0.73-0.91) in CKD3; probably reduced MACE (0.78, 0.62-0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40-0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant. CONCLUSIONS Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn.
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Affiliation(s)
- C M Messow
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK
| | - C Isles
- Medical Unit, Dumfries and Galloway Royal Infirmary, Dumfries DG1 4AP, UK
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Bertoluci MC, Moreira RO, Faludi A, Izar MC, Schaan BD, Valerio CM, Bertolami MC, Chacra AP, Malachias MVB, Vencio S, Saraiva JFK, Betti R, Turatti L, Fonseca FAH, Bianco HT, Sulzbach M, Bertolami A, Salles JEN, Hohl A, Trujilho F, Lima EG, Miname MH, Zanella MT, Lamounier R, Sá JR, Amodeo C, Pires AC, Santos RD. Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM). Diabetol Metab Syndr 2017; 9:53. [PMID: 28725272 PMCID: PMC5512820 DOI: 10.1186/s13098-017-0251-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 06/30/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. MAIN BODY The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. CONCLUSIONS Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.
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Affiliation(s)
- Marcello Casaccia Bertoluci
- Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2400, Porto Alegre, RS 90035-003 Brazil
- Serviço de Medicina Interna, Hospital de Clínicas de Porto Alegre (HCPA), UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903 Brazil
| | - Rodrigo Oliveira Moreira
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rua Moncorvo Filho, 90, Rio de Janeiro, RJ 20211-340 Brazil
- Faculdade de Medicina de Valença (FMV), Rua Sebastião Dantas Moreira, 40, Valença, RJ 27600-000 Brazil
- Faculdade de Medicina da Universidade Presidente Antônio Carlos (FAME/UNIPAC), Av. Juiz de Fora, 1100, Juiz De Fora, MG 36048-000 Brazil
| | - André Faludi
- Instituto Dante Pazzanese de Cardiologia, Av. Dante Pazzanese, 500, São Paulo, SP 04012-180 Brazil
| | - Maria Cristina Izar
- Universidade Federal de São Paulo (UNIFESP), Rua Loefgren, 1350, São Paulo, SP 04040-001 Brazil
| | | | - Cynthia Melissa Valerio
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rua Moncorvo Filho, 90, Rio de Janeiro, RJ 20211-340 Brazil
| | - Marcelo Chiara Bertolami
- Instituto Dante Pazzanese de Cardiologia, Av. Dante Pazzanese, 500, São Paulo, SP 04012-180 Brazil
| | - Ana Paula Chacra
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
| | | | - Sérgio Vencio
- Universidade Federal de Goiás (UFG), 1ª Avenida, s/n, Setor Leste Universitário, Goiânia, GO 74605-020 Brazil
| | - José Francisco Kerr Saraiva
- Pontifícia Universidade Católica de Campinas (PUC-Campinas), Av. John Boyd Dunlop, s/n, Campinas, SP 13059-900 Brazil
| | - Roberto Betti
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
| | - Luiz Turatti
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
| | | | - Henrique Tria Bianco
- Universidade Federal de São Paulo (UNIFESP), Rua Loefgren, 1350, São Paulo, SP 04040-001 Brazil
| | - Marta Sulzbach
- Instituto Dante Pazzanese de Cardiologia, Av. Dante Pazzanese, 500, São Paulo, SP 04012-180 Brazil
| | - Adriana Bertolami
- Instituto Dante Pazzanese de Cardiologia, Av. Dante Pazzanese, 500, São Paulo, SP 04012-180 Brazil
| | - João Eduardo Nunes Salles
- Faculdade de Ciências, Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr, 112, São Paulo, SP 01221-020 Brazil
| | - Alexandre Hohl
- Universidade Federal de Santa Catarina (UFSC), Rua Profa. Maria Flora Pausewang, s/n, Florianópolis, SC 88040-970 Brazil
| | - Fábio Trujilho
- Clínica de Endocrinologia e Metabologia, Av. Tancredo Neves, 1632/708, Salvador, BA 41820-020 Brazil
| | - Eduardo Gomes Lima
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
| | - Marcio Hiroshi Miname
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
| | | | - Rodrigo Lamounier
- Centro de Diabetes de Belo Horizonte, Rua Niquel, 31, Belo Horizonte, MG 30220-280 Brazil
| | | | - Celso Amodeo
- Instituto Dante Pazzanese de Cardiologia, Av. Dante Pazzanese, 500, São Paulo, SP 04012-180 Brazil
| | - Antonio Carlos Pires
- Faculdade de Medicina de São José do Rio Preto, Av. Brg. Faria Lima, 5416, São José do Rio Preto, SP 15090-000 Brazil
| | - Raul D. Santos
- Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil
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Yang QQ, He XY, Wu HY, Zhang CQ, Zou SY, Lang TQ, Sun SSM, Liu QQ. Subchronic feeding study of high-free-lysine transgenic rice in Sprague-Dawley rats. Food Chem Toxicol 2017; 105:214-222. [PMID: 28442410 DOI: 10.1016/j.fct.2017.04.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 04/18/2017] [Accepted: 04/19/2017] [Indexed: 12/24/2022]
Abstract
Lysine is considered to be the first essential amino acid in rice. An elite High-Free-Lysine transgenic line HFL1 was previously produced by metabolic engineering to regulate lysine metabolism. In this study, a 90-day toxicology experiment was undertaken to investigate the potential health effect of feeding different doses of HFL1 rice to Sprague-Dawley rats. During the trial, body weight gain, food consumption and food efficiency were recorded, and no adverse effect was observed in rats fed transgenic (T) rice diets compared with non-transgenic (N) or control diets. At both midterm and final assessments, hematological parameters and serum chemistry were measured, and organ weights and histopathology were examined at the end of the trial. There was no diet-related difference in most hematological or serum chemistry parameters or organ weights between rats fed the T diets and those fed the N or control diets. Some parameters were found to differ between T groups and their corresponding N and/or control groups, but no adverse histological effect was observed. Taken together, the data from the current trial demonstrates that high lysine transgenic rice led to no adverse effect in Sprague-Dawley rats given a diet containing up to 70% HFL1 rice in 90 days.
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Affiliation(s)
- Qing-Qing Yang
- Key Laboratory of Crop Genetics and Physiology of Jiangsu Province / Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou 225009, China; State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Xiao-Yun He
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Hong-Yu Wu
- Key Laboratory of Crop Genetics and Physiology of Jiangsu Province / Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou 225009, China
| | - Chang-Quan Zhang
- Key Laboratory of Crop Genetics and Physiology of Jiangsu Province / Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou 225009, China; Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province / Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China
| | - Shi-Ying Zou
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Tian-Qi Lang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Samuel Sai-Ming Sun
- State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province / Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.
| | - Qiao-Quan Liu
- Key Laboratory of Crop Genetics and Physiology of Jiangsu Province / Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou 225009, China; Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province / Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.
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Screening for chronic kidney disease in Canadian indigenous peoples is cost-effective. Kidney Int 2017; 92:192-200. [PMID: 28433383 DOI: 10.1016/j.kint.2017.02.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 01/23/2017] [Accepted: 02/02/2017] [Indexed: 01/02/2023]
Abstract
Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Primary outcomes were presented as incremental cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life-year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in comparison to usual care. Restricting the model to screening in communities accessed only by air travel (CKD prevalence 34.4%), this ratio fell to $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was $52,480/QALY. The model was robust to changes in influential variables when tested in univariate sensitivity analyses. Probabilistic sensitivity analysis found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93% of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted screening and treatment for CKD using point-of-care testing equipment in rural Canadian indigenous populations is cost-effective, particularly in remote air access-only communities with the highest risk of CKD and kidney failure. Evaluation of targeted screening initiatives with cluster randomized controlled trials and integration of screening into routine clinical visits in communities with the highest risk is recommended.
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Chung CM, Lin MS, Hsu JT, Hsiao JF, Chang ST, Pan KL, Lin CL, Lin YS. Effects of statin therapy on cerebrovascular and renal outcomes in patients with predialysis advanced chronic kidney disease and dyslipidemia. J Clin Lipidol 2017; 11:422-431.e2. [PMID: 28502499 DOI: 10.1016/j.jacl.2017.01.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/02/2017] [Accepted: 01/02/2017] [Indexed: 01/17/2023]
Abstract
BACKGROUND Treatment with statin may be beneficial for patients with chronic kidney disease (CKD). However, the debate over the clinical importance of statin in patients with predialysis advanced CKD remains unresolved. OBJECTIVES The objective of the article was to evaluate the effect of statin on mortality, cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and dyslipidemia. METHODS Data on predialysis advanced CKD patients were retrieved from the National Health Insurance Research Database based on the guidelines for prescribing regular erythropoietin-stimulating agent in CKD patients. Patients with dyslipidemia were further selected and divided into 2 groups by their statin use after the prescribed erythropoietin-stimulating agent. All-cause mortality and cerebrovascular and renal outcomes were analyzed after propensity score matching. RESULTS There were 2016 and 14,412 patients in the statin and nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years, respectively. After 1:2 propensity score matching, the annual all-cause mortality rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per 1000 person-years; P < .001; hazard ratio: 0.73; 95% confidence interval: 0.68-080). The annual risk of ischemic stroke (P = .186) and intracranial hemorrhage (P = .322) were not significantly different between the 2 groups. The nonstatin group had a higher risk of dialysis than the statin group (1269.45 vs 1095.00 per 1000 person-years; P = .002). Adverse events were not significant between the 2 groups. CONCLUSIONS Statins may reduce the all-cause mortality and reduced the risk of dialysis in patients with predialysis advanced CKD and dyslipidemia. However, statins have no impact on ischemic-hemorrhage stroke.
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Affiliation(s)
- Chang-Min Chung
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ming-Shyan Lin
- Division of Cardiology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Jen-Te Hsu
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ju-Feng Hsiao
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Shih-Tai Chang
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Li Pan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chun-Liang Lin
- Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yu-Sheng Lin
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
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Li YH, Ueng KC, Jeng JS, Charng MJ, Lin TH, Chien KL, Wang CY, Chao TH, Liu PY, Su CH, Chien SC, Liou CW, Tang SC, Lee CC, Yu TY, Chen JW, Wu CC, Yeh HI. 2017 Taiwan lipid guidelines for high risk patients. J Formos Med Assoc 2017; 116:217-248. [PMID: 28242176 DOI: 10.1016/j.jfma.2016.11.013] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 11/26/2016] [Indexed: 12/20/2022] Open
Abstract
In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C <55 mg/dL can be considered in ACS patients with DM. After treating LDL-C to target, non-HDL-C can be considered as a secondary target for patients with TG ≥ 200 mg/dL. The suggested non-HDL-C target is < 100 mg/dL in ACS and CAD patients. For patients with ischemic stroke or transient ischemic attack presumed to be of atherosclerotic origin, statin therapy is beneficial and LDL-C < 100 mg/dL is the suggested target. For patients with symptomatic carotid stenosis or intracranial arterial stenosis, in addition to antiplatelets and blood pressure control, LDL-C should be lowered to < 100 mg/dL. Statin is necessary for DM patients with CV disease and the LDL-C target is < 70 mg/dL. For diabetic patients who are ≥ 40 years of age, or who are < 40 years of age but have additional CV risk factors, the LDL-C target should be < 100 mg/dL. After achieving LDL-C target, combination of other lipid-lowering agents with statin is reasonable to attain TG < 150 mg/dL and HDL-C >40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3-5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.
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Affiliation(s)
- Yi-Heng Li
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
| | - Kwo-Chang Ueng
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Jiann-Shing Jeng
- Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
| | - Min-Ji Charng
- Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan
| | - Tsung-Hsien Lin
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Hsing Chao
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
| | - Ping-Yen Liu
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
| | - Cheng-Huang Su
- Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Shih-Chieh Chien
- Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chia-Wei Liou
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Sung-Chun Tang
- Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Chuan Lee
- Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Tse-Ya Yu
- Department of Internal Medicine, Far-Eastern Memorial Hospital, Taipei, Taiwan
| | - Jaw-Wen Chen
- Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chau-Chung Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-I Yeh
- Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
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Khedri M, Szummer K, Carrero JJ, Jernberg T, Evans M, Jacobson SH, Spaak J. Systematic underutilisation of secondary preventive drugs in patients with acute coronary syndrome and reduced renal function. Eur J Prev Cardiol 2017; 24:724-734. [DOI: 10.1177/2047487317693950] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Masih Khedri
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Karolina Szummer
- Section of Cardiology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Juan-Jesus Carrero
- Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Tomas Jernberg
- Section of Cardiology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Marie Evans
- Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Stefan H Jacobson
- Division of Nephrology, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Spaak
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
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Cho EY, Myoung C, Park HS, Kim AJ, Ro H, Chang JH, Lee HH, Chung W, Jung JY. Efficacy of Statin Treatment in Early-Stage Chronic Kidney Disease. PLoS One 2017; 12:e0170017. [PMID: 28081262 PMCID: PMC5231363 DOI: 10.1371/journal.pone.0170017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 12/26/2016] [Indexed: 11/19/2022] Open
Abstract
Chronic kidney disease (CKD) represents a major medical challenge and frequently coexists with cardiovascular disease (CVD), which can be treated by statin trerapy. However, whether statin treatment affects renal progression and outcomes in CKD patients remains unclear. We retrospectively reviewed CKD patients at Gachon University Gil Medical Center from 2003–2013. From a total of 14,497 CKD patients, 858 statin users were paired with non-users and analyze with propensity score matching was performed. The outcomes of this study were creatinine doubling, renal death, all-cause mortality, and interactive factors for composite outcomes. Statins were prescribed to 13.5% of the study subjects. Hazard ratios (HRs) [95% confidence intervals (CIs)] for statin treatment for the doubling of serum creatinine levels were significant only in CKD patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and were 0.744 (0.635–0.873) in the unmatched cohort and 0.767 (0.596–0.986) in the matched cohort. In analyses of secondary outcomes, the HRs (95% CIs) for all-cause mortality were 0.655 (0.502–0.855) in the unmatched cohort and 0.537 (0.297–0.973) in the matched cohort. The HRs (95% CIs) for statin therapy for composite outcomes among patients with and without an eGFR ≥30 mL/min/1.73 m2 were 0.764 (0.613–0.952) and 1.232 (0.894–1.697), respectively (P for interaction, 0.017). Thus, statin treatment may have beneficial effects on renal progression and all-cause mortality only for the patients with early- stage CKD.
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Affiliation(s)
- Eun Yeong Cho
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
| | - Chana Myoung
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
| | - Hong-suk Park
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
| | - Ae Jin Kim
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
| | - Han Ro
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
| | - Jae Hyun Chang
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
| | - Hyun Hee Lee
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
| | - Wookyung Chung
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
| | - Ji Yong Jung
- Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea
- Division of Nephrology, Department of Internal Medicine Gachon University School of Medicine, Incheon, Republic of Korea
- * E-mail:
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Visconti L, Benvenga S, Lacquaniti A, Cernaro V, Bruzzese A, Conti G, Buemi M, Santoro D. Lipid disorders in patients with renal failure: Role in cardiovascular events and progression of chronic kidney disease. J Clin Transl Endocrinol 2016; 6:8-14. [PMID: 29067238 PMCID: PMC5644460 DOI: 10.1016/j.jcte.2016.08.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 07/18/2016] [Accepted: 08/16/2016] [Indexed: 12/29/2022] Open
Abstract
The spectrum of lipid disorders in chronic kidney disease (CKD) is usually characterized by high triglycerides and reduced high dense lipoprotein (HDL), associated with normal or slightly reduced low dense lipoprotein (LDL)-cholesterol. This dyslipidemia is associated with an increased risk for atherosclerotic cardiovascular disease. Keys for the cardiovascular risk reduction in these patients are lowering the number and modifying the composition of the cholesterol-carrying atherogenic lipoprotein particles. Statins have an important role in primary prevention of cardiovascular events and mortality in non-hemodialyzed CKD patients. The benefits in terms of progression of renal failure are contradictory. Patient education regarding dietary regimen should be part of the CKD clinical management.
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Affiliation(s)
- Luca Visconti
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Salvatore Benvenga
- Interdepartment Program of Molecular & Clinical Endocrinology and Women's Endocrine Health, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Antonio Lacquaniti
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Valeria Cernaro
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Annamaria Bruzzese
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Giovanni Conti
- Unit of Pediatric Nephrology, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Michele Buemi
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
| | - Domenico Santoro
- Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, University Hospital, AOU Policlinico G. Martino, Messina, Italy
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Brar S, Ye F, James M, Hemmelgarn B, Klarenbach S, Pannu N. Statin Use and Survival After Acute Kidney Injury. Kidney Int Rep 2016; 1:279-287. [PMID: 29142930 PMCID: PMC5678614 DOI: 10.1016/j.ekir.2016.08.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 07/15/2016] [Accepted: 08/08/2016] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION The incidence of acute kidney injury (AKI) in hospitalized patients is rising, and survivors are at high risk for cardiovascular events and mortality. Effective strategies that improve long-term outcomes of AKI are unknown. METHODS A retrospective cohort study was performed between 2008 and 2011. All subjects were followed until 31 March 2013, with a minimum follow-up of 2 years. Participants were adults 18 years of age or older, who developed AKI during a hospitalization and had chronic kidney disease (CKD) following discharge (n = 19,707 mean age 69.9 years, mean postdischarge estimated glomerular filtration rate (eGFR) 43.0 ml/min/1.73 m2). Exposure to statins was examined prior to the index hospitalization as well as within 2 years following hospital discharge. The primary outcome was mortality; secondary outcomes included all-cause re-hospitalization and cardiovascular events. RESULTS Within 2 years of discharge, only 38.3% of the participants were prescribed a statin. After adjustment for comorbidities, statin use prior to admission, demographics, baseline kidney function, and a number of other factors, statin use was associated with lower mortality (hazard ratio, 0.74; 95% confidence interval, 0.69, 0.79) in AKI survivors with CKD. Patients who received a statin also had a lower risk of all cause rehospitalization (adjusted hazarad ratio, 0.90; 95% confidence interval, 0.85, 0.94). Statin use was not associated with a reduction in cardiovascular events. DISCUSSION Among AKI survivors with CKD, statin use was associated with a lower risk of mortality and rehospitalization rates. This finding suggests that there is an opportunity to improve postdischarge care in AKI survivors.
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Affiliation(s)
- Sandeep Brar
- Department of Nephrology, University of Toronto, Toronto, Ontario, Canada
| | - Feng Ye
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Matthew James
- Department of Medicine, Division of Nephrology, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Brenda Hemmelgarn
- Department of Medicine, Division of Nephrology, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Scott Klarenbach
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Institute of Health Economics, Edmonton, Alberta, Canada
| | - Neesh Pannu
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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