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Kelly DM, Kelleher EM, Rothwell PM. The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease. Stroke 2025; 56:1069-1081. [PMID: 39851054 PMCID: PMC11932449 DOI: 10.1161/strokeaha.124.047070] [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] [Indexed: 01/25/2025]
Abstract
Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.
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Affiliation(s)
- Dearbhla M. Kelly
- Wolfson Centre for the Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences (D.M.K., P.M.R.)
| | - Eoin M. Kelleher
- Nuffield Department of Clinical Neurosciences (E.M.K.), University of Oxford, United Kingdom
| | - Peter M. Rothwell
- Wolfson Centre for the Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences (D.M.K., P.M.R.)
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2
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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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Xu W, Yau YK, Pan Y, Tse ETY, Lam CLK, Wan EYF. Effectiveness and safety of using statin therapy for the primary prevention of cardiovascular diseases in older patients with chronic kidney disease who are hypercholesterolemic: a target trial emulation study. THE LANCET. HEALTHY LONGEVITY 2025; 6:100683. [PMID: 40058388 DOI: 10.1016/j.lanhl.2025.100683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 01/01/2025] [Accepted: 01/03/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND There remains a scarcity of evidence on initiating statin therapy for the primary prevention of cardiovascular diseases among older adults with chronic kidney disease due to the under-representation of this population in randomised controlled trials. This study aimed to evaluate the effectiveness and safety of using statin therapy for the primary prevention of cardiovascular diseases in older adults (aged 75-84 years) and very old adults (aged ≥85 years) with chronic kidney disease. METHODS Using territory-wide public electronic health records in Hong Kong, patients older than 60 years with chronic kidney disease and with hyperlipidaemia (defined as elevated LDL cholesterol of ≥2·6 mmol/L) were identified for inclusion in the analyses and were included on a rolling basis in each calendar month from January, 2008, to December, 2015. Patients were categorised into different age groups (ie, 60-74 years, 75-84 years, and ≥85 years) for analysis, and the 60-74 years age group was used as a benchmark group to test the validity of our emulated trial since the effect of statin therapy is well established in this age group. The framework of target trial emulation was adopted to investigate the association between statin therapy and the risk of overall cardiovascular disease incidence, specific cardiovascular disease subtypes (ie, myocardial infarction, heart failure, and stroke), and all-cause mortality, as well as major adverse events (ie, myopathies and liver dysfunction). The primary outcome was overall cardiovascular disease incidence. The hazard ratios for the outcomes were estimated by pooled logistic models in the intention-to-treat analysis and the per-protocol analysis. FINDINGS 711 966 person-trials from 96 trials were eligible for inclusion in the study. 19 423 unique individuals with chronic kidney disease aged 60-74 years, 22 565 unique individuals with chronic kidney disease aged 75-84 years, and 8811 unique individuals with chronic kidney disease aged 85 years and older were identified for inclusion in the analyses. In patients aged 75-84 years, a significant risk reduction was observed for overall cardiovascular disease incidence in both the intention-to-treat analysis (hazard ratio [HR] 0·94 [95% CI 0·89-0·99]) and in the per-protocol analysis (0·86 [0·80-0·92]) and for all-cause mortality (0·87 [0·82-0·91] in the intention-to-treat analysis and 0·78 [0·72-0·84] in the per-protocol analysis). This risk reduction was also observed among patients aged 85 years and older for cardiovascular diseases (HR 0·88 [0·79-0·99] in the intention-to-treat analysis and 0·81 [0·71-0·92] in the per-protocol analysis), and for all-cause mortality (0·89 [0·81-0·98] in the intention-to-treat analysis and 0·80 [0·71-0·91] in the per-protocol analysis). Substantial risk reduction for myocardial infarction, heart failure, and stroke were also observed across all age groups. No significantly increased risk of myopathies or liver dysfunction was observed in any of the age groups. INTERPRETATION Statin therapy is beneficial for hypercholesterolemic older patients with chronic kidney disease aged 75 years and older regarding the primary prevention against cardiovascular diseases and all-cause mortality, without posing an increased risk of major adverse events. The benefits and safety persist in those aged 85 years and older. FUNDING National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau).
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Affiliation(s)
- Wanchun Xu
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Yuk Kam Yau
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Yanyu Pan
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Emily Tsui Yee Tse
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Family Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Cindy Lo Kuen Lam
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Family Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Eric Yuk Fai Wan
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health (D(2)4H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China; The Institute of Cardiovascular Science and Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Advanced Data Analytics for Medical Science, Hong Kong Special Administrative Region, China.
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4
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Yao Y, Xiong J, Wang MY. Dose-response relationship between lipids and all-cause mortality in the dialysis population: a meta-analysis. BMC Nephrol 2025; 26:55. [PMID: 39905322 PMCID: PMC11796159 DOI: 10.1186/s12882-025-03981-z] [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: 08/23/2024] [Accepted: 01/24/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND The use of lipid-lowering drugs in the dialysis population has been controversial and there is no target for the dialysis population. OBJECTIVES To elucidate the dose-response relationship between lipids and all-cause mortality in the dialysis population. METHODS Computer searches of PubMed, Embase, Web of Science, CNKI, and Wanfang. Data were conducted to collect published cohort studies on lipids and all-cause mortality in the dialysis population from home and abroad up to February 2023. Meta-analysis was applied to calculate the combined effect size (Hazard ratio) and its 95% confidence interval and dose-response relationship by applying Stata17.0. RESULTS A total of 11 publications with a cumulative total of 106,808 individuals were included. All-cause mortality was statistically different between the highest dose total cholesterol (TC) group and the low TC group (HR = 0.82, 95% CI = 0.75-0.90, P < 0.05). The TC range for lower all-cause mortality is > 140.5 mg/dL, and on this basis, TC in the range of 180-220 mg/dL may have a better prognosis for dialysis population. There was a nonlinear relationship between Non-high-density lipoprotein cholesterol (NHDL-C) cholesterol and all-cause mortality, with no statistical difference between the high and low dose group. In contrast, Low-density lipoprotein cholesterol (LDL-C) masked its association with all-cause mortality due to changes in death spectrum, differences in relative time risks, and other factors. In the 50-450 mg/dL range, all-cause mortality in the dialysis population was positively associated with triglycerides (TG), with a 2.5% increase in all-cause mortality per 50 mg/dL increase in TG (HR = 1.025, 95% CI = 1.003-1.048, P = 0.01). CONCLUSION TC is a target for monitoring the dialysis population, which has the lowest all-cause mortality in the range of 180-220 mg/dL. However, NHDL-C and LDL-C monitoring is not clinically meaningful. Increased TG can contribute to the risk of higher all-cause mortality in dialysis patients.
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Affiliation(s)
- Ye Yao
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jing Xiong
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Mi-Yuan Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Blum MF, Neuen BL, Grams ME. Risk-directed management of chronic kidney disease. Nat Rev Nephrol 2025:10.1038/s41581-025-00931-8. [PMID: 39885336 DOI: 10.1038/s41581-025-00931-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 02/01/2025]
Abstract
The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.
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Affiliation(s)
- Matthew F Blum
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brendon L Neuen
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Morgan E Grams
- New York University Grossman School of Medicine, New York, NY, USA.
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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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Jairoun AA, Ping CC, Ibrahim B, Al Jawamis DF, Al Jaberi AK, Dawoud T, Mohammed KJ, El-Dahiyat F, Shahwan M. Effect of statins and antihyperglycemics on chronic kidney disease in patients with type 2 diabetes mellitus: a retrospective cohort study with a 12-year follow-up. J Pharm Policy Pract 2024; 18:2414293. [PMID: 39776464 PMCID: PMC11703420 DOI: 10.1080/20523211.2024.2414293] [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: 04/08/2024] [Accepted: 10/02/2024] [Indexed: 01/11/2025] Open
Abstract
Background Chronic Kidney Disease (CKD) represents a significant worldwide health challenge, with far-reaching implications for both patients and healthcare systems. This study aimed to identify the incidence of CKD at stages 3-5, analyzed the impact of statin and other antihyperglycemic interventions, on the CKD progression in individuals with T2DM. Methods This was a single-center retrospective cohort study based on data derived from electronic medical records (EMR) of UAE populations with diabetes mellitus, registered at outpatient clinics at Tawam Hospital in Al Ain, UAE, between January 2011 and December 2021. T2DM patients aged ≥ 18 years who had serum HbA1c level ≥ 6.5% and using one of the statin therapies were inclusion criteria. Patients with T1DM, who had undergone permanent renal replacement therapy, with under 1 year of follow-up and missing or incomplete data were excluded from the study. The collected data encompassed socio-demographics, detailed medical history, anthropometric measurements, laboratory analyses, clinical parameters, disease characteristics, and medications. Results Our study included a cohort of 1,003 individuals. We observed 388 subjects developed CKD stages 3-5 across an average monitoring duration of 11.7 years. This resulted in a cumulative incidence of 38.7%, translating to an incidence rate of 38 cases per 1000 person-years. There was a statistically significant difference in the cumulative incidence of CKD stages 3 ± 5 according to statin therapy (P = 0.047). High intensity statin users are more likely to develop a CKD stage 3-5 compared to low/moderate intensity users and to no statin users respectively (44.3% vs 37.9%), (44.3% vs 30.9%). Conversely, the use of Biguanides was associated with a decreased probability of CKD progression (37.9% vs. 52.8%; P = 0.001), whereas Insulin users demonstrated a heightened risk (54.2% vs. 34.1%; P < 0.001). Conclusion The findings emphasise the pivotal role of personalised treatment strategies, particularly concerning statin therapy and other medications, in populations at high risk.
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Affiliation(s)
- Ammar Abdulrahman Jairoun
- Discipline of clinical pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Pulau Pinang, Malaysia
| | - Chong Chee Ping
- Discipline of clinical pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Pulau Pinang, Malaysia
| | | | | | | | - Tasnim Dawoud
- Pharmacy Department, Tawam Hospital, SEHA, Al Ain, United Arab Emirates
| | | | - Faris El-Dahiyat
- Clinical Pharmacy Program, College of Pharmacy, Al Ain University, Al Ain, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
| | - Moyad Shahwan
- College of Pharmacy and Health Sciences, Ajman University, Ajman, UAE
- Centre of Medical and Bio allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
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Lin YC, Lai TS, Chen YT, Chou YH, Chen YM, Hung KY, Tu YK. Comparative efficacy and choice of lipid-lowering drugs for cardiovascular and kidney outcomes in patients with chronic kidney disease: A systematic review and network meta-analysis. J Formos Med Assoc 2024:S0929-6646(24)00474-1. [PMID: 39389802 DOI: 10.1016/j.jfma.2024.09.037] [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: 08/08/2024] [Revised: 09/07/2024] [Accepted: 09/27/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND The effect of exact classes of lipid-lowering drugs (LLDs) on preventing major adverse cardiovascular events (MACEs) and poor renal outcomes is not well characterized in the chronic kidney disease (CKD) population. METHODS We performed a frequentist random-effects network meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effect of the LLDs in non-dialysis CKD patients. The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for relevant trials published before March 31, 2024. The primary outcome was the incidence of MACEs. The secondary outcomes comprised all-cause mortality, end-stage kidney disease, changes in estimated glomerular filtration rate (eGFR) and proteinuria, and safety. RESULTS Forty-nine eligible RCTs with 77,826 participants with non-dialysis CKD were included. With moderate confidence in the evidence, rosuvastatin and atorvastatin showed statistically significantly more efficacy in reducing the risk of MACE, with a pooled risk ratio of 0.55 (95% CI 0.33-0.91) for rosuvastatin and 0.67 (0.49-0.90) for atorvastatin, respectively, compared with the control group. For the change in the eGFR, atorvastatin (mean difference [MD], 1.40; 95% CI, 0.61 to 2.18), rosuvastatin (MD, 1.73; 95% CI, 0.63 to 2.83), and statin plus ezetimibe (MD, 2.35; 95% CI, 0.44 to 4.26) showed statistically significant increases in the mean eGFR. CONCLUSION In patients with non-dialysis CKD, there is sufficient evidence to show that rosuvastatin and atorvastatin were statistically significantly more effective and preferable in reducing the risk of MACE and increasing the mean eGFR compared with the control group.
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Affiliation(s)
- Yi-Chih Lin
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City, Taiwan
| | - Tai-Shuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Yi-Ting Chen
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsiang Chou
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yung-Ming Chen
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kuan-Yu Hung
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Kang Tu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Health Data Research Center, National Taiwan University, Taipei, Taiwan.
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Freese Ballegaard EL, Lerkevang Grove E, Kamper AL, Feldt-Rasmussen B, Gislason G, Torp-Pedersen C, Carlson N. Acute Myocardial Infarction and Chronic Kidney Disease: A Nationwide Cohort Study on Management and Outcomes from 2010 to 2022. Clin J Am Soc Nephrol 2024; 19:1263-1274. [PMID: 39024026 PMCID: PMC11469784 DOI: 10.2215/cjn.0000000000000519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/12/2024] [Indexed: 07/20/2024]
Abstract
Key Points Retrospective study of guideline-directed management of myocardial infarction in patients with and without CKD from 2010 to 2022. CKD was associated with lower rate of guideline-directed management and worse prognosis. Uptake of guideline-directed management increased and prognosis improved in both groups during the study period. Background CKD is present in >30% of patients with acute myocardial infarction (MI) and has been associated with lower rates of guideline-directed management and worse prognosis. We investigated the use of guideline-directed management and mortality risk in patients with and without CKD. Methods A nationwide cohort study based on health care registers encompassing all patients ≥18 years hospitalized with first-time MI in Denmark from 2010 to 2022 was conducted. CKD was defined as an eGFR <60 ml/min per 1.73 m2. Probability of guideline-directed management and risk of all-cause mortality in patients with and without CKD were calculated from adjusted multivariable logistic and Cox regression models with probabilities and risks standardized to the distribution of confounders in the population. Results In total, we identified 21,009 patients who met eligibility criteria. The median age was 72 years, and 61% of patients were male; the median eGFR was 82 ml/min per 1.73 m2, and 21% of patients had CKD. The 30-day probabilities of coronary angiography and revascularization were 71% (95% confidence interval [CI], 69% to 72%) and 78% (95% CI, 77% to 79%), P < 0.001 and 52% (95% CI, 50% to 54%) and 58% (95% CI, 58% to 59%), P < 0.001, in patients with and without CKD, respectively. Probabilities increased during the study period (P for trend 0.05, 0.03, 0.02, and 0.03, respectively). In patients with and without CKD, the probability of dual antiplatelet therapy was 67% (95% CI, 65% to 68%) and 70% (95% CI, 69% to 71%), P = 0.001, whereas the probability of lipid-lowering treatment was 76% (95% CI, 75% to 78%) and 82% (95% CI, 81% to 83%), P < 0.001, respectively. The associated 1-year mortality was 21% (95% CI, 20% to 22%) and 16.4% (95% CI, 16% to 17%) in patients with and without CKD, respectively. with decreasing mortality rates in both groups during the study period (P for trend 0.03 and 0.01). Conclusions Although survival after MI improved for all patients, CKD continued to be associated with lower use of guideline-directed management and higher mortality.
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Affiliation(s)
- Ellen Linnea Freese Ballegaard
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Medicine, Zealand University Hospital, Roskilde, Denmark
| | - Erik Lerkevang Grove
- Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Lise Kamper
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Gunnar Gislason
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- The Danish Heart Foundation, Copenhagen, Denmark
- Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark
| | - Christian Torp-Pedersen
- Department of Cardiology, Copenhagen University Hospital - North Zealand, Hillerød, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Nicholas Carlson
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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Wei S, Liu N, Fu Y, Sun M. Novel insights into modifiable risk factors for arteriovenous fistula failure and the importance of CKD lipid profile: A meta-analysis. J Vasc Access 2024; 25:1416-1431. [PMID: 36951426 DOI: 10.1177/11297298221115557] [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] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Arteriovenous fistula (AVF) failure can occur in patients undergoing hemodialysis (HD). In this study, we explored the correlation between hyperlipidemia and AVF failure in patients undergoing HD. Moreover, we compared the lipid profiles of patients with chronic kidney disease (CKD) with those of healthy people to provide a basis for lipid-lowering in patients undergoing HD. METHOD AND ANALYSIS We searched PubMed, Web of Science, Embase, the Cochrane library, CNKI, CBM, the China Science Periodical Database, and the China Science and Technology Journal Database. The final search was conducted on August 31, 2021, and the search period was restricted between 2000 and August 31, 2021, without publication restrictions. All studies met the inclusion criteria, and the influences of sex, age, geographical location, diagnosis method, and publication year were excluded. The data were analyzed using the random-effects model and the fixed-effects model. RESULTS Twenty-eight studies were included in the meta-analysis with 121,666 patients in the CKD group and 1714 patients in the AVF failure group. Triglyceride concentration in patients with CKD was higher than in healthy subjects (MD: -31.56, 95% CI: -41.23 to -21.90, p < 0.00001). A high total cholesterol (TC) concentration (MD: 6.97, 95% CI: 2.19-11.74, p = 0.004) and a high low-density lipoprotein cholesterol (LDL-C) concentration (MD: 23.83, 95% CI: 18.48-29.18, p < 0.00001) were associated with AVF failure. Furthermore, HDL-C was lower in the AVF failure group than in the AVF patency group (MD: -2.68, 95% CI: -4.60 to -0.76, p = 0.006). CONCLUSION Our analysis indicates that the AVF failure may be related to the increase of TC/LDL-C and the decrease of HDL-C. Although current guidelines do not consider intensive lipid-lowering therapy as necessary in patients undergoing HD, our research indicates that patients with AVF undergoing HD may need regular TC/LDL-C-lowering therapy to prevent AVF failure. However, this issue still needs well designed prospective trials.
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Affiliation(s)
- Shizhuo Wei
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
| | - Naimeng Liu
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yingli Fu
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Mindan Sun
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
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11
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Guo J, Jiang Z, Xia Y, Wang H, Tang Q, Meng B. The association between statin use and diabetic nephropathy in US adults: data from NHANES 2005 - 2018. Front Endocrinol (Lausanne) 2024; 15:1381746. [PMID: 38726340 PMCID: PMC11079199 DOI: 10.3389/fendo.2024.1381746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Background A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.
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Affiliation(s)
| | | | | | | | - Qun Tang
- Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, China
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12
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Strippoli GFM, Green SC. Actioning the findings of hard endpoint clinical trials as they emerge in the realm of chronic kidney disease care: a review and a call to action. Clin Kidney J 2024; 17:sfae035. [PMID: 38425707 PMCID: PMC10903297 DOI: 10.1093/ckj/sfae035] [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: 01/19/2024] [Indexed: 03/02/2024] Open
Abstract
Fewer than half of patients treated with hemodialysis survive 5 years. Multiple therapeutics are used to address the complications of advanced chronic kidney disease but most have not been found to improve clinical outcomes. Clinical trials of treatment innovations for chronic kidney diseases and dialysis care have been suboptimal in number and quality. Recent trials are changing this trend. Practice and policy change when new evidence emerges remains frequently impeded by resource and organizational constraints and accordingly, clinical practice guidelines are updated years or decades after definitive evidence is produced. Ultimately, practice change in health systems is slow, leading to impaired uptake of effective medical interventions and lower value healthcare, although innovations in rapid guideline production are emerging. What can be done to ensure that conclusive evidence is taken up in practice, policy and healthcare funding? We use the example of the recently published hard endpoint study "Comparison of high-dose HDF with high-flux HD" (CONVINCE) (hemodiafiltration versus hemodialysis), to explain how a new trial can impact on medical knowledge and change in practices. We (i) assess how the trial can be placed in the context of the totality of the evidence, (ii) define whether or not further trials of convective dialysis therapies are still needed and (iii) examine whether the evidence for convective therapies is now ready to inform practice, policy and funding change. When looking at CONVINCE in the context of the totality of evidence, we show that it addresses dialysis quality improvement priorities and is consistent with other trials evaluating convective dialysis therapies, and that the evidence for convective dialysis therapies is now definitive. Once updated evidence for cost-effectiveness in specific healthcare settings and patient-reported outcomes become available, we should therefore determine whether or not clinical practice guidelines should recommend uptake of convective dialysis therapies routinely, and move on to evaluating other treatments.
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Affiliation(s)
- Giovanni F M Strippoli
- Sydney School of Public Health, The University of Sydney, NSW Australia
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J) University of Bari Aldo Moro, Bari, Italy
| | - Suetonia C Green
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
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13
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Khatiwada N, Hong Z. Potential Benefits and Risks Associated with the Use of Statins. Pharmaceutics 2024; 16:214. [PMID: 38399268 PMCID: PMC10892755 DOI: 10.3390/pharmaceutics16020214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/13/2024] [Accepted: 01/22/2024] [Indexed: 02/25/2024] Open
Abstract
HMG-CoA reductase inhibitors, commonly known as statins, are the primary treatment choice for cardiovascular diseases, which stand as the leading global cause of mortality. Statins also offer various pleiotropic effects, including improved endothelial function, anti-inflammatory properties, reduced oxidative stress, anti-thrombotic effects, and the stabilization of atherosclerotic plaques. However, the usage of statins can be accompanied by a range of adverse effects, such as the development of type 2 diabetes mellitus, muscular symptoms, liver toxicity, kidney diseases, cataracts, hemorrhagic strokes, and psychiatric complications. These issues are referred to as statin-associated symptoms (SAS) and are relatively infrequent in clinical trials, making it challenging to attribute them to statin use definitively. Therefore, these symptoms can lead to significant problems, necessitating dose adjustments or discontinuation of statin therapy. This review aims to provide a comprehensive overview of the mechanism of action, potential advantages, and associated risks of statin utilization in clinical settings.
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Affiliation(s)
| | - Zhongkui Hong
- Department of Mechanical Engineering, Texas Tech University, Lubbock, TX 79409, USA;
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14
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Barayev O, Hawley CE, Wellman H, Gerlovin H, Hsu W, Paik JM, Mandel EI, Liu CK, Djoussé L, Gaziano JM, Gagnon DR, Orkaby AR. Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease. JAMA Netw Open 2023; 6:e2346373. [PMID: 38055276 PMCID: PMC10701610 DOI: 10.1001/jamanetworkopen.2023.46373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 10/24/2023] [Indexed: 12/07/2023] Open
Abstract
Importance There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). Objective To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. Design, Setting, and Participants This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Exposure Statin initiation vs none. Main Outcomes and Measures Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Results Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. Conclusions and Relevance In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.
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Affiliation(s)
- Odeya Barayev
- Ben Gurion University of the Negev, Be’er Sheva, Israel
| | - Chelsea E. Hawley
- New England Geriatric Research Education and Clinical Center, Bedford and Boston, Massachusetts
| | - Helen Wellman
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
| | - Hanna Gerlovin
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
| | - Whitney Hsu
- VA Boston Healthcare System, Department of Pharmacy, Boston, Massachusetts
| | - Julie M. Paik
- New England Geriatric Research Education and Clinical Center, Bedford and Boston, Massachusetts
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Ernest I. Mandel
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Christine K. Liu
- Section of Geriatrics, Department of Medicine, Stanford University School of Medicine, Stanford, California
- Geriatric Research Education and Clinical Center, Palo Alto VA Medical Center, Palo Alto, California
| | - Luc Djoussé
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
- Division of Aging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - J. Michael Gaziano
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
- Division of Aging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - David R. Gagnon
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
| | - Ariela R. Orkaby
- New England Geriatric Research Education and Clinical Center, Bedford and Boston, Massachusetts
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston
- Division of Aging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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15
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Lin YC, Tsao HM, Lai TS, Chen YT, Chou YH, Lin SL, Chen YM, Hung KY, Tu YK. Effect of Lipid-Lowering Drugs on Renal and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Dyslipidemia: A Retrospective Cohort Study. Clin Pharmacol Ther 2023; 114:1366-1374. [PMID: 37750432 DOI: 10.1002/cpt.3060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/16/2023] [Indexed: 09/27/2023]
Abstract
The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.
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Affiliation(s)
- Yi-Chih Lin
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City, Taiwan
| | - Hsiao-Mei Tsao
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tai-Shuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Ting Chen
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Division of Blood Purification, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Hsiang Chou
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shuei-Liong Lin
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan
- Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
| | - Yung-Ming Chen
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kuan-Yu Hung
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Kang Tu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
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16
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Virani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, Dixon DL, Fearon WF, Hess B, Johnson HM, Kazi DS, Kolte D, Kumbhani DJ, LoFaso J, Mahtta D, Mark DB, Minissian M, Navar AM, Patel AR, Piano MR, Rodriguez F, Talbot AW, Taqueti VR, Thomas RJ, van Diepen S, Wiggins B, Williams MS. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2023; 82:833-955. [PMID: 37480922 DOI: 10.1016/j.jacc.2023.04.003] [Citation(s) in RCA: 137] [Impact Index Per Article: 68.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/24/2023]
Abstract
AIM The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
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17
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Virani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, Dixon DL, Fearon WF, Hess B, Johnson HM, Kazi DS, Kolte D, Kumbhani DJ, LoFaso J, Mahtta D, Mark DB, Minissian M, Navar AM, Patel AR, Piano MR, Rodriguez F, Talbot AW, Taqueti VR, Thomas RJ, van Diepen S, Wiggins B, Williams MS. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2023; 148:e9-e119. [PMID: 37471501 DOI: 10.1161/cir.0000000000001168] [Citation(s) in RCA: 419] [Impact Index Per Article: 209.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/22/2023]
Abstract
AIM The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
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Affiliation(s)
| | | | | | | | | | | | - Dave L Dixon
- Former Joint Committee on Clinical Practice Guideline member; current member during the writing effort
| | - William F Fearon
- Society for Cardiovascular Angiography and Interventions representative
| | | | | | | | - Dhaval Kolte
- AHA/ACC Joint Committee on Clinical Data Standards
| | | | | | | | - Daniel B Mark
- Former Joint Committee on Clinical Practice Guideline member; current member during the writing effort
| | | | | | | | - Mariann R Piano
- Former Joint Committee on Clinical Practice Guideline member; current member during the writing effort
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18
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Di-(2-ethylhexyl) Phthalate Limits the Lipid-Lowering Effects of Simvastatin by Promoting Protein Degradation of Low-Density Lipoprotein Receptor: Role of PPARγ-PCSK9 and LXRα-IDOL Signaling Pathways. Antioxidants (Basel) 2023; 12:antiox12020477. [PMID: 36830035 PMCID: PMC9952605 DOI: 10.3390/antiox12020477] [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: 01/05/2023] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Dialysis prevents death from uremia in patients with end-stage renal disease (ESRD). Nevertheless, during hemodialysis, circulating levels of di-(2-ethylhexyl) phthalate (DEHP) are increased due to phthalates leaching from medical tubes. Statins are an effective therapy for reducing the risks associated with cardiovascular diseases in patients with chronic kidney disease; however, the mechanism by which statins fail to reduce cardiovascular events in hemodialysis ESRD patients remains unclear. In this study, we investigated whether DEHP and its metabolites interfere with the lipid-lowering effect of statins in hepatocytes. In Huh7 cells, treatment with DEHP and its metabolites abolished the simvastatin-conferred lipid-lowering effect. Mechanistically, DEHP down-regulated the expression of low-density lipoprotein receptor (LDLR) and led to a decrease in LDL binding, which was mediated by the activation of the PPARγ-PCSK9 and LXRα-IDOL signaling pathways. Additionally, the NOX-ROS-TRPA1 pathway is involved in the DEHP-mediated inhibition of LDLR expression and LDL binding activity. Blockage of this pathway abrogated the DEHP-mediated inhibition in the LDLR expression and LDL binding of simvastatin. Collectively, DEHP induces the activation of the NOX-ROS-TRPA1 pathway, which in turn activates PPARγ-PCSK9- and LXRα-IDOL-dependent signaling, and, ultimately, diminishes the statin-mediated lipid-lowering effect in hepatocytes.
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19
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Abdul Rahman N, Ghani M, Kausar S, Sadiqa A, Khalid A. Revealing the Connection Between Hemodialysis and Sexual Physiology in Women With End-Stage Renal Disease. Cureus 2023; 15:e35184. [PMID: 36960251 PMCID: PMC10029979 DOI: 10.7759/cureus.35184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2023] [Indexed: 02/21/2023] Open
Abstract
INTRODUCTION In the recent past, the procedure of hemodialysis has frequently been opted for patients with end-stage renal disease (ESRD) around the globe. In such patients, the concern of sexual dysfunction is highly prevalent, which causes psychological as well as social deterioration in these patients. Wretchedly, this issue has been ignored in developing countries like Pakistan because of social and cultural constraints. Objectives: The aim was to measure and compare Female Sexual Functions of Dialysis (FSFI) scores among three comparative groups: healthy controls, pre-dialysis patients, and hemodialysis patients. METHODS A comparative cross-sectional study was carried out with 60 females aged 22-50 years in which 20 were healthy (controls) and 40 were patients with ESRD; of these 40, 20 were taking only oral medicines (pre-dialysis) and 20 were also receiving hemodialysis (hemodialysis). Married women who could read Urdu and were living with live spouses were included, and those with any psychological or psychiatric illness were excluded. Data was collected through a Likert-scaled questionnaire, Urdu translation of the FSFI questionnaire, and scores of each domain were analyzed. Single-tail one-way ANOVA was used to observe the significant difference among the three comparative groups. RESULTS A strong statistical difference was observed among the hemodialysis, pre-dialysis, and healthy control groups when these three study groups were compared for the mean scores of all related domains of FSFI questtionarie. In each female sexual domain, i.e. Desire, Arousal, Lubrication, Orgasm, Satisfaction, and Pain, the diseased groups (pre-dialysis and hemodialysis) showed lower sexual scores than the healthy group. The lowest scores were observed in the pre-dialysis group (16.4 ± 6.8) and the highest were noticed in the healthy group (29.9 ± 1.8); the hemodialysis group (23.3 ± 5.0) expressed a moderate pattern of scores in each sexual domain. CONCLUSION ESRD female patients who were receiving hemodialysis along with routine oral medications showed improved sexual physiology (with better FSFI scores) compared to those who were without hemodialysis.
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Affiliation(s)
| | - Mansoor Ghani
- Internal Medicine, University of Health Sciences, Lahore, PAK
| | - Samina Kausar
- Nursing, Institute of Nursing, University of Health Sciences, Lahore, PAK
| | - Ayesha Sadiqa
- Physiology, CMH (Combined Military Hospitals) Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | - Asma Khalid
- Nursing, Gulfreen Nursing College, Avicenna Medical College Lahore, Lahore, PAK
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20
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Advances in the Pharmacological Management of Diabetic Nephropathy: A 2022 International Update. Biomedicines 2023; 11:biomedicines11020291. [PMID: 36830828 PMCID: PMC9953496 DOI: 10.3390/biomedicines11020291] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/24/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Its pathogenesis encompasses functional alterations involving elevated intraglomerular and systemic pressure, increased activity of the renin-angiotensin system (RAS) and oxidative stress, and the eventual development of renal fibrosis. The management of DN involves the optimization of blood pressure (BP) and blood glucose targets. However, treatment of these risk factors slows down but does not stop the progression of DN. Innovative pharmacologic therapies for dyslipidemia and type 2 diabetes mellitus (T2DM) could play a key role in bridging this gap and attenuating the residual risk of DN beyond traditional risk factor management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and inhibitors of mineralocorticoid receptor-mediated sodium reabsorption are recently introduced drug classes that have been shown to have positive effects on kidney function in individuals with T2DM. The aim of this review is to provide an update on the therapeutic options available in order to prevent or slow the onset and progression of DN in diabetic patients.
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Kassam N, Surani S, Hameed K, Aghan E, Mayenga R, Matei I, Jengo G, Bakshi F, Mbithe H, Orwa J, Udeani G, Somji S. Magnitude, Distribution and Contextual Risk Enhancing Predictors of High 10-Year Cardiovascular Risk Among Diabetic Patients in Tanzania. Patient Relat Outcome Meas 2023; 14:87-96. [PMID: 37152069 PMCID: PMC10162395 DOI: 10.2147/prom.s405392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 04/20/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of death worldwide. In Diabetics, ASCVD is associated with poor prognosis and a higher case fatality rate compared with the general population. Sub-Saharan Africa is facing an epidemiological transition with ASCVD being prevalent among young adults. To date, over 20 million people have been living with DM in Africa, Tanzania being one of the five countries in the continent reported to have a higher prevalence. This study aimed to identify an individual's 10-year ASCVD absolute risk among a diabetic cohort in Tanzania and define contextual risk enhancing factors. Methods A prospective observational study was conducted at the Aga Khan hospital, Mwanza, for a period of 8 months. The hospital is a 42-bed district-level hospital in Tanzania. Individuals 10-year risk was calculated based on the ASCVD 2013 risk calculator by ACC/AHA. Pearson's chi-square or Fischer's exact test was used to compare categorical and continuous variables. Multivariable analysis was applied to determine contextual factors for those who had a high 10-year risk of developing ASCVD. Results The overall cohort included 573 patients. Majority of the individuals were found to be hypertensive (n = 371, 64.7%) and obese (n = 331, 58%) having a high 10-year absolute risk (n = 343, 60%) of suffering ASCVD. The study identified duration of Diabetes Mellitus (>10 years) (OR 8.15, 95% CI 5.25-14.42), concomitant hypertension (OR 1.82 95% CI 1.06-3.06), Diabetic Dyslipidemia (OR 1.44, 95% CI 1.08-1.92) and deranged serum creatinine (OR 1.03, 95% CI 1.02-1.03) to be the risk enhancing factors amongst our population. Conclusion The study confirms the majority of diabetic individuals in the lake region of Tanzania to have a high 10-year ASCVD risk. The high prevalence of obesity, hypertension and dyslipidemia augments ASCVD risk but provides interventional targets for health-care workers to decrease these alarming projections.
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Affiliation(s)
- Nadeem Kassam
- Department of Internal Medicine, Aga Khan Hospital, Mwanza, Tanzania
- Correspondence: Nadeem Kassam, Email
| | - Salim Surani
- Department of Pharmacy, A&M University, College Station, TX, USA
| | - Kamran Hameed
- Department of Internal Medicine, Aga Khan Hospital, Dar es Salaam, Tanzania
| | - Eric Aghan
- Department of Family Medicine Aga Khan University Medical College, Dar es Salaam, Tanzania
| | - Robert Mayenga
- Department of Internal Medicine, Aga Khan Hospital, Mwanza, Tanzania
| | - Iris Matei
- Department of Internal Medicine, Aga Khan Hospital, Mwanza, Tanzania
| | - Gijsberta Jengo
- Department of Internal Medicine, Aga Khan Hospital, Mwanza, Tanzania
| | - Fatma Bakshi
- Department of Internal Medicine, Aga Khan Hospital, Dar es Salaam, Tanzania
| | - Hanifa Mbithe
- Department of Internal Medicine, Aga Khan Hospital, Dar es Salaam, Tanzania
| | - James Orwa
- Department of Population Health, Aga Khan University, Nairobi, Kenya
| | - George Udeani
- Department of Pharmacy, A&M University, College Station, TX, USA
| | - Samina Somji
- Department of Internal Medicine, Aga Khan Hospital, Dar es Salaam, Tanzania
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Sourij H, Edlinger R, Prischl FC, Kaser S, Horn S, Antlanger M, Paulweber B, Aberer F, Brix J, Cejka D, Stingl H, Kautzky-Willer A, Schmaldienst S, Clodi M, Rosenkranz A, Mayer G, Oberbauer R, Säemann M. [Diabetic kidney disease (update 2023) : Position paper of the Austrian Diabetes Association and the Austrian Society for Nephrology]. Wien Klin Wochenschr 2023; 135:182-194. [PMID: 37101040 PMCID: PMC10133372 DOI: 10.1007/s00508-022-02147-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2022] [Indexed: 04/28/2023]
Abstract
Epidemiological investigations have shown that approximately 2-3% of all Austrians have diabetes mellitus with renal involvement, leaving 250,000 people in Austria affected. The risk of occurrence and progression of this disease can be attenuated by lifestyle interventions as well as optimization of blood pressure, blood glucose control and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society of Nephrology for the diagnostic and treatment strategies of diabetic kidney disease.
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Affiliation(s)
- Harald Sourij
- Klinische Abteilung für Endokrinologie und Diabetologie, Trials Unit für Interdisziplinäre Metabolische Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.
| | - Roland Edlinger
- 3. Medizinische Abteilung mit Stoffwechselerkrankungen und Nephrologie, Klinik Hietzing, Wien, Österreich
| | - Friedrich C Prischl
- Abteilung für Innere Medizin IV, Klinikum Wels-Grieskirchen, Wels, Österreich
| | - Susanne Kaser
- Universitätsklinik für Innere Medizin I, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Sabine Horn
- Abteilung für Innere Medizin, LKH Villach, Villach, Österreich
| | - Marlies Antlanger
- Universitätsklinik für Innere Medizin 2, Kepler Universitätsklinikum Linz, Linz, Österreich
| | - Bernhard Paulweber
- Universitätsklinik für Innere Medizin I, Landeskrankenhaus Salzburg, Uniklinikum der PMU, Salzburg, Österreich
| | - Felix Aberer
- Klinische Abteilung für Endokrinologie und Diabetologie, Medizinische Universität Graz, Graz, Österreich
| | - Johanna Brix
- 1. Medizinischen Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Klinik Landstraße, Wien, Österreich
| | - Daniel Cejka
- Abteilung für Innere Medizin 3, Ordensklinikum Linz, Elisabethinen, Linz, Österreich
| | - Harald Stingl
- Abteilung für Innere Medizin, LKH Melk, Melk, Österreich
| | - Alexandra Kautzky-Willer
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | | | - Martin Clodi
- Abteilung für Innere Medizin, Krankenhaus Barmherzige Brüder Linz, Linz, Österreich
| | - Alexander Rosenkranz
- Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Gert Mayer
- Nephrologie und Hypertensiologie, Universitätsklinik für Innere Medizin IV, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Rainer Oberbauer
- Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Marcus Säemann
- 6. Medizinische Abteilung mit Nephrologie & Dialyse, Klinik Ottakring, Wien, Österreich
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Aeschbacher‐Germann M, Kaiser N, Speierer A, Blum MR, Bauer DC, Del Giovane C, Aujesky D, Gencer B, Rodondi N, Moutzouri E. Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria. J Am Heart Assoc 2022; 12:e026551. [PMID: 36565207 PMCID: PMC9973576 DOI: 10.1161/jaha.122.026551] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.
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Affiliation(s)
- Martina Aeschbacher‐Germann
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland,Institute of Primary Health Care (BIHAM)University of BernSwitzerland
| | - Nathalie Kaiser
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland,Institute of Primary Health Care (BIHAM)University of BernSwitzerland
| | - Alexandre Speierer
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland
| | - Manuel R. Blum
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland,Institute of Primary Health Care (BIHAM)University of BernSwitzerland
| | - Douglas C. Bauer
- Departments of Medicine and Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoCA
| | | | - Drahomir Aujesky
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland
| | - Baris Gencer
- Institute of Primary Health Care (BIHAM)University of BernSwitzerland,Division of CardiologyGeneva University HospitalsGenevaSwitzerland
| | - Nicolas Rodondi
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland,Institute of Primary Health Care (BIHAM)University of BernSwitzerland
| | - Elisavet Moutzouri
- Department of General Internal Medicine, InselspitalBern University Hospital, University of BernSwitzerland,Institute of Primary Health Care (BIHAM)University of BernSwitzerland
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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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Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract 2022; 28:923-1049. [PMID: 35963508 PMCID: PMC10200071 DOI: 10.1016/j.eprac.2022.08.002] [Citation(s) in RCA: 221] [Impact Index Per Article: 73.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
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Affiliation(s)
| | | | - S Sethu Reddy
- Central Michigan University, Mount Pleasant, Michigan
| | | | | | | | | | | | - Daniel Einhorn
- Scripps Whittier Diabetes Institute, La Jolla, California
| | | | | | - Rajesh Garg
- Lundquist Institute/Harbor-UCLA Medical Center, Torrance, California
| | | | | | | | | | | | - Darin Olson
- Colorado Mountain Medical, LLC, Avon, Colorado
| | | | | | - Archana R Sadhu
- Houston Methodist; Weill Cornell Medicine; Texas A&M College of Medicine; Houston, Texas
| | | | - Carla Stec
- American Association of Clinical Endocrinology, Jacksonville, Florida
| | | | - Katherine R Tuttle
- University of Washington and Providence Health Care, Seattle and Spokane, Washington
| | | | | | | | - Sandra L Weber
- University of South Carolina School of Medicine-Greenville, Prisma Health System, Greenville, South Carolina
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Hsiao CC, Yeh JK, Li YR, Sun WC, Fan PY, Yen CL, Chen JS, Lin C, Chen KH. Statin uses in adults with non-dialysis advanced chronic kidney disease: Focus on clinical outcomes of infectious and cardiovascular diseases. Front Pharmacol 2022; 13:996237. [PMID: 36249758 PMCID: PMC9561676 DOI: 10.3389/fphar.2022.996237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Background: Statins are commonly used for cardiovascular disease (CVD) prevention. Observational studies reported the effects on sepsis prevention and mortality improvement. Patients with chronic kidney disease (CKD) are at high risk for CVD and infectious diseases. Limited information is available for statin use in patients with non-dialysis CKD stage V. Method: The retrospective observational study included patients with non-dialysis CKD stage V, with either de novo statin use or none. Patients who were prior statin users and had prior cardiovascular events were excluded. The key outcomes were infection-related hospitalization, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, hospitalization for heart failure, or non-fatal stroke), and all-cause mortality. The data were retrieved from the Chang Gung Research Database (CGRD) from January 2001 to December 2019. Analyses were conducted with Cox proportional hazard regression models in the propensity score matching (PSM) cohort. Result: A total of 20,352 patients with CKD stage V were included (1,431 patients were defined as de novo statin users). After PSM, 1,318 statin users were compared with 1,318 statin non-users. The infection-related hospitalization (IRH) rate was 79.3 versus 94.3 per 1,000 person-years in statin users and statin non-users, respectively [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.74–0.93, p = 0.002]. The incidence of MACE was 38.9 versus 55.9 per 1,000 person-years in statin users and non-users, respectively (HR, 0.72; 95% CI 0.62–0.83, p < 0.001). The all-cause mortality did not differ between statin users and non-users, but statin users had lower infection-related mortality than non-users (HR, 0.59; 95% CI 0.38–0.92, p = 0.019). Conclusion:De novo use of statin in patients with non-dialysis CKD stage V reduced the incidence of cardiovascular events, hospitalization, and mortality for infectious disease. The study results reinforced the benefits of statin in a wide range of patients with renal impairment before maintenance dialysis.
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Affiliation(s)
- Ching-Chung Hsiao
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jih-Kai Yeh
- Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yan-Rong Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wei-Chiao Sun
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Yi Fan
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chieh-Li Yen
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Jung-Sheng Chen
- Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Chihung Lin
- Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- *Correspondence: Chihung Lin, ; Kuan-Hsing Chen,
| | - Kuan-Hsing Chen
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- *Correspondence: Chihung Lin, ; Kuan-Hsing Chen,
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Wang X, Li J, Wang T, Zhang Z, Li Q, Ma D, Chen Z, Ju J, Xu H, Chen K. Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials. Front Cardiovasc Med 2022; 9:929020. [PMID: 36093163 PMCID: PMC9452733 DOI: 10.3389/fcvm.2022.929020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 08/01/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease. Methods We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin. Results Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), P < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), P < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), P < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), P < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations. Conclusion Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to. Systematic review registration [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].
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Affiliation(s)
- Xinyi Wang
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jingen Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Tongxin Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zihao Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Qiuyi Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Dan Ma
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhuo Chen
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jianqing Ju
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hao Xu
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Keji Chen
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Statins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter? Int J Mol Sci 2022; 23:ijms23169326. [PMID: 36012589 PMCID: PMC9409457 DOI: 10.3390/ijms23169326] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/12/2022] [Accepted: 08/15/2022] [Indexed: 11/25/2022] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality are decreasing in high-income countries, but ASCVD remains the leading cause of morbidity and mortality in high-income countries. Over the past few decades, major risk factors for ASCVD, including LDL cholesterol (LDL-C), have been identified. Statins are the drug of choice for patients at increased risk of ASCVD and remain one of the most commonly used and effective drugs for reducing LDL cholesterol and the risk of mortality and coronary artery disease in high-risk groups. Unfortunately, doctors tend to under-prescribe or under-dose these drugs, mostly out of fear of side effects. The latest guidelines emphasize that treatment intensity should increase with increasing cardiovascular risk and that the decision to initiate intervention remains a matter of individual consideration and shared decision-making. The purpose of this review was to analyze the indications for initiation or continuation of statin therapy in different categories of patient with high cardiovascular risk, considering their complexity and comorbidities in order to personalize treatment.
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Wu X, Zhou L, Zhan X, Wen Y, Wang X, Feng X, Wang N, Peng F, Wu J. Low-Density Lipoprotein Cholesterol and Mortality in Peritoneal Dialysis. Front Nutr 2022; 9:910348. [PMID: 35938138 PMCID: PMC9351358 DOI: 10.3389/fnut.2022.910348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/25/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundIn dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients.MethodsIn this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models.ResultsOf 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72).ConclusionLow and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.
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Affiliation(s)
- Xianfeng Wu
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- Clinical Research Center for Chronic Kidney Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Xianfeng Wu,
| | - Lei Zhou
- Evergreen Tree Nephrology Association, Guangzhou, China
| | - Xiaojiang Zhan
- Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yueqiang Wen
- Department of Nephrology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaoyang Wang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoran Feng
- Department of Nephrology, Jiujiang No. 1 People’s Hospital, Jiujiang, China
| | - Niansong Wang
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- Clinical Research Center for Chronic Kidney Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Fenfen Peng
- Department of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Junnan Wu
- Department of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw Hospital, Hangzhou, China
- Junnan Wu,
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Yuan Q, Tang B, Zhang C. Signaling pathways of chronic kidney diseases, implications for therapeutics. Signal Transduct Target Ther 2022; 7:182. [PMID: 35680856 PMCID: PMC9184651 DOI: 10.1038/s41392-022-01036-5] [Citation(s) in RCA: 156] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 05/20/2022] [Accepted: 05/24/2022] [Indexed: 12/11/2022] Open
Abstract
Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that is characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity and oxidative stress are the driving force for the loss of nephron including tubules, glomerulus, and endothelium. NLRP3 inflammasome signaling, MAPK signaling, PI3K/Akt signaling, and RAAS signaling involves in lipotoxicity. The upregulated Nox expression and the decreased Nrf2 expression result in oxidative stress directly. The injured renal resident cells release proinflammatory cytokines and chemokines to recruit immune cells such as macrophages from bone marrow. NF-κB signaling, NLRP3 inflammasome signaling, JAK-STAT signaling, Toll-like receptor signaling, and cGAS-STING signaling are major signaling pathways that mediate inflammation in inflammatory cells including immune cells and injured renal resident cells. The inflammatory cells produce and secret a great number of profibrotic cytokines such as TGF-β1, Wnt ligands, and angiotensin II. TGF-β signaling, Wnt signaling, RAAS signaling, and Notch signaling evoke the activation of myofibroblasts and promote the generation of ECM. The potential therapies targeted to these signaling pathways are also introduced here. In this review, we update the key signaling pathways of lipotoxicity, oxidative stress, inflammation, and myofibroblasts activation in kidneys with chronic injury, and the targeted drugs based on the latest studies. Unifying these pathways and the targeted therapies will be instrumental to advance further basic and clinical investigation in CKD.
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Affiliation(s)
- Qian Yuan
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ben Tang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chun Zhang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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HDL and Kidney Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1377:163-170. [PMID: 35575929 DOI: 10.1007/978-981-19-1592-5_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Serum lipid profiles, as well as HDL can be altered in patients with kidney diseases. There are various types of kidney diseases, including nephrotic syndrome and chronic kidney disease. In patients with nephrotic syndrome, plasma levels of HDL cholesterol and ApoA-I were within or below the normal limits. The HDL cholesterol: total cholesterol ratio decreased compared to healthy individuals. In patients with chronic kidney disease (CKD), reverse cholesterol transport function of HDL is impaired, and CKD also affects the composition and function of HDL. Cardiovascular disease (CVD) is the severe complication of CKD. Furthermore, HDL might also be a potential target for the prevention of cardiovascular complications associated with CKD.
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Goicoechea M, Álvarez V, Segarra A, Polaina M, Martín-Reyes G, Robles NR, Escudero V, Orellana C, Bea Granell S, de Juan-Ribera J, Fernández Lucas M, Graña JM, Reque J, Sánchez Hernández R, Villamayor S, Górriz JL. Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO). Nefrologia 2022; 42:301-310. [PMID: 36210619 DOI: 10.1016/j.nefroe.2022.05.005] [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: 11/13/2020] [Revised: 05/13/2021] [Accepted: 06/13/2021] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND AND OBJECTIVE To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2 (51.7% of patients had eGFR <60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c ≥160mg/dL and 29.3% ≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use remained stable. CONCLUSION In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.
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Affiliation(s)
- Marian Goicoechea
- Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Vicente Álvarez
- Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, Spain
| | - Alfonso Segarra
- Servicio de Nefrología, Hospital Arnau de Vilanova, Lérida, Spain
| | - Manuel Polaina
- Servicio de Nefrología, Complejo Hospitalario de Jaén, Jaén, Spain
| | - Guillermo Martín-Reyes
- Unidad de Gestión Clínica de Nefrología, Hospital Regional Universitario, Universidad de Málaga, Málaga, Spain; Servicio de Nefrología, IBIMA, REDinREN (RD16/0009/0006), Málaga, Spain
| | | | - Verónica Escudero
- Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, Spain
| | - Cristhian Orellana
- Servicio de Nefrología, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Sergio Bea Granell
- Servicio de Nefrología, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
| | | | | | - Jose Maria Graña
- Servicio de Nefrología, Hospital Universitario de la Ribera, Alzira, Valencia, Spain
| | - Javier Reque
- Servicio de Nefrología, Hospital Rey Don Jaime, Castellón, Spain
| | - Rosa Sánchez Hernández
- Servicio de Nefrología, Hospital Universitario General de Villalba, Villalba, Madrid, Spain
| | | | - Jose Luis Górriz
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
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Dellepiane S, Marengo M, D'Arezzo M, Donati G, Fabbrini P, Lacquaniti A, Ronco C, Cantaluppi V. The Next Evolution of HemoDialysis eXpanded: From a Delphi Questionnaire-Based Approach to the Real Life of Italian Dialysis Units. Blood Purif 2022; 51:943-952. [PMID: 35231902 PMCID: PMC9808684 DOI: 10.1159/000522038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 01/17/2022] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Impact assessment of new technologies in chronic hemodialysis (HD) is challenging due to HD patient frailty, the complexity of HD clinical trials and practice variability among countries. Among the most recent HD innovations, medium cut-off (MCO) dialyzers present an optimized membrane geometry that provides enhanced clearances for middle and large molecular weight uremic toxins (UT). These toxins are poorly cleared by available HD techniques and largely contribute to patient morbidity and mortality. The aim of this paper is to assess the available clinical evidence about MCO membranes and to identify the next steps needed to generate conclusive data on their use in HD. METHODS With this purpose, we first reviewed and compared the current HD technologies aimed to improve the clearance of middle and large UT; subsequently, we used a Delphi questionnaire to identify and discuss the consensus about MCO efficacy within a large sample of the Italian Nephrology community. RESULTS AND CONCLUSIONS Our investigation gathered a significant degree of consensus on the beneficial role of MCO membrane and expanded HD. Finally, we used our results to propose future trial designs and clinical investigations aimed to improve evidence quality about the use of these membranes in the present clinical scenario of dialysis units.
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Affiliation(s)
- Sergio Dellepiane
- Department of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Mario D'Arezzo
- Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti − Ancona University Hospital, Ancona, Italy
| | - Gabriele Donati
- Nephrology Dialysis and Renal Transplantation Unit, St. Orsola University Hospital, Bologna, Italy
| | - Paolo Fabbrini
- Nephrology and Dialysis Unit, San Gerardo Hospital and Milano Bicocca University, Monza, Italy
| | | | - Claudio Ronco
- Department of Medicine, University of Padova, Padova, Italy
- Division of Nephrology, Dialysis and Kidney Transplantation Unit, International Renal Research Institute Vicenza (IRRIV), “San Bortolo” Hospital, Vicenza, Italy
| | - Vincenzo Cantaluppi
- Nephrology and Kidney Transplantation Unit, Department of Translational Medicine, University of Piemonte Orientale (UPO), “Maggiore della Carità” University Hospital, Novara, Italy
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Funamizu T, Iwata H, Chikata Y, Doi S, Endo H, Wada H, Naito R, Ogita M, Kato Y, Okai I, Dohi T, Kasai T, Isoda K, Okazaki S, Miyauchi K, Minamino T. A Prognostic Merit of Statins in Patients with Chronic Hemodialysis after Percutaneous Coronary Intervention-A 10-Year Follow-Up Study. J Clin Med 2022; 11:jcm11020390. [PMID: 35054080 PMCID: PMC8780570 DOI: 10.3390/jcm11020390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/04/2022] [Accepted: 01/09/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Patients with end-stage renal disease (ESRD) on chronic hemodialysis who are complicated by coronary artery disease (CAD) are at very high risk of cardiovascular (CV) events and mortality. However, the prognostic benefit of statins, which is firmly established in the general population, is still under debate in this particular population. METHODS As a part of a prospective single-center percutaneous coronary intervention (PCI) registry database, this study included consecutive patients on chronic hemodialysis who underwent PCI for the first time between 2000 and 2016 (n = 201). Participants were divided into 2 groups by following 2 factors, such as (1) with or without statin, and (2) with or without high LDL-C (> and ≤LDL-C = 93 mg/dL, median) at the time of PCI. The primary endpoint was defined as CV death, and the secondary endpoints included all-cause and non-CV death, and 3 point major cardiovascular adverse events (3P-MACE) which is the composite of CV death, non-fatal myocardial infarction and stroke. The median and range of the follow-up period were 2.8, 0-15.2 years, respectively. RESULTS Kaplan-Meier analyses showed significantly lower cumulative incidences of primary and secondary endpoints other than non-CV deaths in patients receiving statins. Conversely, no difference was observed when patients were divided by the median LDL-C at the time of PCI (p = 0.11). Multivariate Cox proportional hazard analysis identified statins as an independent predictor of reduced risk of CV death (Hazard ratio of statin use: 0.43, 95% confidence interval 0.18-0.88, p = 0.02), all-cause death (HR: 0.50, 95%CI 0.29-0.84, p = 0.007) and 3P-MACE (HR: 0.50, 95%CI 0.25-0.93, p = 0.03). CONCLUSIONS Statins were associated with reduced risk of adverse outcomes in patients with ESRD following PCI.
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Affiliation(s)
- Takehiro Funamizu
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Hiroshi Iwata
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
- Correspondence: ; Tel.: +81-3-3813-3111
| | - Yuichi Chikata
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Shinichiro Doi
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Hirohisa Endo
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Hideki Wada
- Department of Cardiology, Juntendo University Shizuoka Hospital, Izunokuni 410-2295, Japan; (H.W.); (M.O.)
| | - Ryo Naito
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Manabu Ogita
- Department of Cardiology, Juntendo University Shizuoka Hospital, Izunokuni 410-2295, Japan; (H.W.); (M.O.)
| | - Yoshiteru Kato
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Iwao Okai
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Tomotaka Dohi
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Takatoshi Kasai
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Kikuo Isoda
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Shinya Okazaki
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Katsumi Miyauchi
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
| | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (T.F.); (Y.C.); (S.D.); (H.E.); (R.N.); (Y.K.); (I.O.); (T.D.); (T.K.); (K.I.); (S.O.); (K.M.); (T.M.)
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Sanchez-Ramirez DC, Singer AG, Kosowan L, Katz A, Polimeni C. Increasing likelihood of prescribing recommended lipid management: Primary care providers' participation in cardiology continuing medical education. CANADIAN FAMILY PHYSICIAN MEDECIN DE FAMILLE CANADIEN 2022; 68:39-46. [PMID: 35063983 PMCID: PMC9810061 DOI: 10.46747/cfp.680139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To explore whether participation in a series of cardiology continuing medical education (CME) activities affects primary care providers' (PCPs') lipid management for their patients. DESIGN This retrospective cohort study used a database of participation in cardiology CME activities (2011 to 2017) linked to electronic medical records. Statistical analyses were completed using logistic regression with generalized estimating equations. SETTING Manitoba. PARTICIPANTS Patients receiving care from 225 PCPs participating in the Manitoba Primary Care Research Network. MAIN OUTCOME MEASURES Recommended lipid management was defined as prescription of statins (yes or no) among patients diagnosed with cardiovascular disease (CVD), patients diagnosed with diabetes mellitus (DM; 40 years or older), and patients diagnosed with chronic kidney disease (CKD; 50 years and older) in 2017. Treatment was identified using the ATC (Anatomical Therapeutic Chemical) system (ATC code C10AA or C10B). RESULTS After adjusting for relevant confounders, the odds of prescribing statins to patients with CVD, DM, or CKD among PCPs who did not participate in the cardiology CME activities were 50%, 55%, and 67% lower, respectively, than among PCPs who participated in 2 or more activities. The odds of prescribing statins to patients with CVD and DM among PCPs who participated in only 1 cardiology CME activity were also 67% and 63% lower, respectively, than among PCPs who participated in 2 or more activities. CONCLUSION Results suggested that PCPs who participated in 2 or more cardiology CME activities were more likely to prescribe recommended lipid management (statins) for adults with CVD, DM, or CKD.
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Affiliation(s)
- Diana C. Sanchez-Ramirez
- Assistant Professor in the College of Rehabilitation Sciences in the Rady Faculty of Health Sciences at the University of Manitoba in Winnipeg.,Correspondence Dr Diana C. Sanchez-Ramirez; e-mail
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Self-Reported Physical Activity and Survival in Adults Treated With Hemodialysis: A DIET-HD Cohort Study. Kidney Int Rep 2021; 6:3014-3025. [PMID: 34901570 PMCID: PMC8640545 DOI: 10.1016/j.ekir.2021.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 08/22/2021] [Accepted: 09/03/2021] [Indexed: 11/04/2022] Open
Abstract
Introduction Regular physical activity is associated with longevity in adults receiving hemodialysis, but it is uncertain whether this association varies by causal pathways (cardiovascular and noncardiovascular). Methods DIET-HD was a prospective, multinational study of adults undergoing hemodialysis across Europe and Argentina. We classified participants as physically inactive, occasionally active (irregularly to once a week), or frequently active (twice a week or more), using a self-reported questionnaire. Potential confounders were balanced across exposure groups using propensity scores. Weighted Cox proportional hazards models with double robust estimators evaluated the association between physical activity and all-cause, cardiovascular, and noncardiovascular mortality. Results Of 8043 participants in DIET-HD, 6147 (76%) had information on physical activity. A total of 2940 (48%) were physically inactive, 1981 (32%) occasionally active, and 1226 (20%) frequently active. In a median follow-up of 3.8 years (19,677 person-years), 2337 (38%) deaths occurred, including 1050 (45%) from cardiovascular causes. After propensity score weighting, occasional physical activity was associated with lower all-cause (adjusted hazard ratio [aHR] = 0.80, 95% CI = 0.72–0.89), cardiovascular (aHR = 0.82, 95% CI = 0.70–0.96), and noncardiovascular (aHR = 0.81, 95% CI = 0.69–0.94) mortality compared with inactivity. Frequent physical activity was associated with lower all-cause (aHR = 0.82, 95% CI = 0.71–0.95) and cardiovascular (aHR = 0.77, 95% CI = 0.62–0.94) mortality, but not noncardiovascular mortality (aHR = 0.88, 95% CI = 0.72–1.08). A dose-dependent association of physical activity with cardiovascular death was observed (P trend = 0.01). Conclusion Compared with self-reported physical inactivity, occasional and frequent physical activities were associated, dose dependently, with lower cardiovascular mortality in adults receiving hemodialysis.
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Majithia A, Bhatt DL, Friedman AN, Miller M, Steg PG, Brinton EA, Jacobson TA, Ketchum SB, Juliano RA, Jiao L, Doyle RT, Granowitz C, Budoff M, Preston Mason R, Tardif JC, Boden WE, Ballantyne CM. Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL. Circulation 2021; 144:1750-1759. [PMID: 34706555 PMCID: PMC8614567 DOI: 10.1161/circulationaha.121.055560] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Supplemental Digital Content is available in the text. Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.
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Affiliation(s)
- Arjun Majithia
- Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, Burlington, MA (A.M.)
| | - Deepak L Bhatt
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.L.B., R.P.M.)
| | - Allon N Friedman
- Department of Medicine, Indiana University School of Medicine, Indianapolis (A.N.F.)
| | - Michael Miller
- Department of Medicine, University of Maryland School of Medicine, Baltimore (M.M.)
| | - Ph Gabriel Steg
- Université de Paris, FACT (French Alliance for Cardiovascular Trials), Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148, France (P.G.S.)
| | | | - Terry A Jacobson
- Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, GA (T.A.J.)
| | - Steven B Ketchum
- Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., L.J., R.T.D., C.G.)
| | - Rebecca A Juliano
- Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., L.J., R.T.D., C.G.)
| | - Lixia Jiao
- Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., L.J., R.T.D., C.G.)
| | - Ralph T Doyle
- Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., L.J., R.T.D., C.G.)
| | - Craig Granowitz
- Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., L.J., R.T.D., C.G.)
| | - Matthew Budoff
- Division of Cardiology, Harbor UCLA Medical Center, Torrance, CA (M.B.)
| | - R Preston Mason
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.L.B., R.P.M.)
| | | | - William E Boden
- Division of Cardiovascular Medicine, Boston Medical Center, MA (W.E.B.)
| | - Christie M Ballantyne
- Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX (C.M.B.)
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Muñoz Ramos P, Gil Giraldo Y, Álvarez-Chiva V, Arroyo D, Sango Merino C, Moncho Francés F, Ocaña J, Reque J, Sánchez-Álvarez E, Górriz JL, Quiroga B. Proteinuria-Lowering Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Chronic Kidney Disease Patients: A Real-World Multicentric Study. Metabolites 2021; 11:metabo11110760. [PMID: 34822418 PMCID: PMC8618891 DOI: 10.3390/metabo11110760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/01/2021] [Accepted: 11/03/2021] [Indexed: 01/22/2023] Open
Abstract
Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) were collected. The evolution of renal function, proteinuria and lipid profile was analyzed during the 1-year follow-up. The cohort included 76 patients (68% male, mean age 66 ± 10 years). The mean baseline creatinine was 1.55 ± 0.77 mg/dL, and the mean eGFR was 52 ± 22 mL/min/1.73 m2. Reductions in LDL-cholesterol, total cholesterol and triglycerides during the first month were 51 ± 25%, 32 ± 25% and 11 ± 40%, respectively, levels that remained stable throughout the first year (p < 0.001 for LDL-cholesterol and total cholesterol trends and p = 0.002 for triglyceride trend). During follow-up, proteinuria improved from 57 (9–481) to 30 (7–520) mg/g (p = 0.021). In addition, eGFR remained stable, and no adverse events were reported. In our cohort, dyslipidemia treatment with PCSK9i was associated with decreased proteinuria in CKD patients, an effect that might be due to reduced lipid nephrotoxicity. Clinical trials are needed to further investigate whether this impact on proteinuria can significantly slow CKD progression in the long term.
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Affiliation(s)
- Patricia Muñoz Ramos
- Nephrology Department, Hospital Universitario de La Princesa, 28006 Madrid, Spain; (P.M.R.); (Y.G.G.); (V.Á.-C.)
| | - Yohana Gil Giraldo
- Nephrology Department, Hospital Universitario de La Princesa, 28006 Madrid, Spain; (P.M.R.); (Y.G.G.); (V.Á.-C.)
| | - Vicente Álvarez-Chiva
- Nephrology Department, Hospital Universitario de La Princesa, 28006 Madrid, Spain; (P.M.R.); (Y.G.G.); (V.Á.-C.)
| | - David Arroyo
- Nephrology Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain;
| | - Cristina Sango Merino
- Nephrology Department, Hospital de Cabueñes, 33394 Gijón, Spain; (C.S.M.); (E.S.-Á.)
| | - Francesc Moncho Francés
- Nephrology Department, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, 46010 Valencia, Spain; (F.M.F.); (J.L.G.)
| | - Javier Ocaña
- Nephrology Department, Fundación Hospital de Alcorcón, 28922 Madrid, Spain;
| | - Javier Reque
- Nephrology Department, Hospital General de Castellón, 12004 Castelló de la Plana, Spain;
| | | | - José Luis Górriz
- Nephrology Department, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, 46010 Valencia, Spain; (F.M.F.); (J.L.G.)
| | - Borja Quiroga
- Nephrology Department, Hospital Universitario de La Princesa, 28006 Madrid, Spain; (P.M.R.); (Y.G.G.); (V.Á.-C.)
- Correspondence: ; Tel.: +34-915-202-200
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Anderson JLC, van der Giet M, Gomes Neto AW, Bakker SJL, Tietge UJF. Statin use and incident cardiovascular events in renal transplant recipients. Eur J Clin Invest 2021; 51:e13594. [PMID: 34042174 PMCID: PMC8596424 DOI: 10.1111/eci.13594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/24/2021] [Accepted: 05/03/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Statins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users. METHOD 622 included RTR (follow-up 5.4 years) were matched based on propensity scores and dichotomized by statin use. Survival analysis was conducted. RESULTS Cox regression showed that statin use was not significantly associated with the compound CV endpoint in a fully adjusted model (HR = 0.81, 95% CI = 0.53-1.24, P = .33). Subgroup analyses in RTR using cyclosporine revealed a strong positive association of statin use with the CV compound outcome in a fully adjusted model (HR = 6.60, 95% CI 1.75-24.9, P = .005). Furthermore, statin use was positively correlated with cyclosporine trough levels (correlation coefficient 0.11, P = .04). CONCLUSION In conclusion, statin use does not significantly decrease incident CV events in an overall RTR cohort, but is independently associated with CV-specific mortality and events in cyclosporine using RTR, possibly due to a bilateral pharmacological interaction.
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Affiliation(s)
- Josephine L C Anderson
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Markus van der Giet
- Medizinische Klinik für Nephrologie und Internistische Intensivtherapie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Antonio W Gomes Neto
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Uwe J F Tietge
- Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
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Hecking M, Karaboyas A, Schernthaner GH, Wanner C. Statin initiation in dialysis patients: The hardship of non-prescription. Atherosclerosis 2021; 337:53-56. [PMID: 34663493 DOI: 10.1016/j.atherosclerosis.2021.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/05/2021] [Accepted: 10/08/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Manfred Hecking
- Department of Internal Medicine III, Clinical Division of Nephrology & Dialysis, Medical University of Vienna, Austria
| | | | - Gerit-Holger Schernthaner
- Department of Internal Medicine II, Clinical Division of Angiology, Medical University of Vienna, Austria.
| | - Christoph Wanner
- Department of Medicine I, Division of Nephrology, Universitätsklinik Würzburg, Germany
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41
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Su G, Saglimbene V, Wong G, Natale P, Ruospo M, Craig JC, Hegbrant J, Carrero JJ, Strippoli GFM. Healthy Lifestyle and Mortality Among Adults Receiving Hemodialysis: The DIET-HD Study. Am J Kidney Dis 2021; 79:688-698.e1. [PMID: 34547395 DOI: 10.1053/j.ajkd.2021.07.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/28/2021] [Indexed: 01/08/2023]
Abstract
RATIONALE & OBJECTIVE A healthy lifestyle promotes cardiovascular health and reduces cardiac-related mortality in the general population but its benefits for people receiving maintenance hemodialysis are uncertain. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 5,483 of 9,757 consecutive adults receiving maintenance hemodialysis (January 2014 to June 2017, median dialysis vintage: 3.6 yrs) in a multinational private dialysis network and with complete lifestyle data. EXPOSURES Based on the American Heart Association's recommendations for cardiovascular prevention, a modified healthy lifestyle score was the sum of four components addressing use of smoking tobacco, physical activity, diet, and control of systolic blood pressure. OUTCOMES Cardiovascular and all-cause mortality. ANALYTICAL APPROACH Adjusted proportional hazards (aHRs) regression analyses with country as a random effect to estimate the associations between lifestyle score (low [0-2 points] as the referent, medium [3-5], and high [6-8]) and mortality. Associations were expressed as aHRs with 95% confidence intervals (CIs). RESULTS During a median of 3.8 years (17,451 person-years in total), there were 2,163 deaths, of which 826 were related to cardiovascular disease. Compared to patients with a low lifestyle score, the aHRs (95% CIs) for all-cause mortality among those with medium and high lifestyle scores were 0.75 (0.65-0.85) and 0.64 (0.54-0.76), respectively. Compared to patients with a low lifestyle score, the aHRs (95% CIs) for cardiovascular mortality among those with medium and high lifestyle scores were 0.73 (0.59-0.91) and 0.65 (0.49-0.85), respectively. LIMITATIONS Self-reported lifestyle, data-driven approach. CONCLUSIONS A healthier lifestyle is associated with lower all-cause and cardiovascular mortality among patients receiving maintenance hemodialysis.
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Affiliation(s)
- Guobin Su
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Department of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou city, Guangdong Province, China; Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou city, Guangdong Province, China; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;; European Renal Nutrition Working Group of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA)
| | - Valeria Saglimbene
- Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, NSW 2006, Australia; Department of Emergency and Organ Transplantation, University of Bari, Bari, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Germaine Wong
- Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, NSW 2006, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Patrizia Natale
- Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, NSW 2006, Australia; Department of Emergency and Organ Transplantation, University of Bari, Bari, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Marinella Ruospo
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Jonathan C Craig
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Jorgen Hegbrant
- Division of Nephrology, Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Juan Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;; European Renal Nutrition Working Group of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA)
| | - Giovanni F M Strippoli
- Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, NSW 2006, Australia; Department of Emergency and Organ Transplantation, University of Bari, Bari, Piazza Giulio Cesare, 70124 Bari, Italy.
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Goicoechea M, Álvarez V, Segarra A, Polaina M, Martín-Reyes G, Robles NR, Escudero V, Orellana C, Bea Granell S, de Juan-Ribera J, Fernández Lucas M, Graña JM, Reque J, Sánchez Hernández R, Villamayor S, Górriz JL. Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO). Nefrologia 2021; 42:S0211-6995(21)00133-8. [PMID: 34389184 DOI: 10.1016/j.nefro.2021.06.004] [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: 11/13/2020] [Revised: 05/13/2021] [Accepted: 06/13/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVE To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable. CONCLUSION In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.
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Affiliation(s)
- Marian Goicoechea
- Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, España.
| | - Vicente Álvarez
- Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, España
| | - Alfonso Segarra
- Servicio de Nefrología, Hospital Arnau de Vilanova, Lérida, España
| | - Manuel Polaina
- Servicio de Nefrología, Complejo Hospitalario de Jaén, Jaén, España
| | - Guillermo Martín-Reyes
- Unidad de Gestión Clínica de Nefrología, Hospital Regional Universitario, Universidad de Málaga, Málaga, España; Servicio de Nefrología, IBIMA, REDinREN (RD16/0009/0006), Málaga, España
| | | | - Verónica Escudero
- Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, España
| | - Cristhian Orellana
- Servicio de Nefrología, Hospital Universitario Puerta del Mar, Cádiz, España
| | - Sergio Bea Granell
- Servicio de Nefrología, Consorcio Hospital General Universitario de Valencia, Valencia, España
| | | | | | - Jose Maria Graña
- Servicio de Nefrología, Hospital Universitario de la Ribera, Alzira, Valencia, España
| | - Javier Reque
- Servicio de Nefrología, Hospital Rey Don Jaime, Castellón, España
| | - Rosa Sánchez Hernández
- Servicio de Nefrología, Hospital Universitario General de Villalba, Villalba, Madrid, España
| | | | - Jose Luis Górriz
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, España
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Efficacy of Statin Treatment According to Baseline Renal Function in Korean Patients with Acute Myocardial Infarction Not Requiring Dialysis Undergoing Newer-Generation Drug-Eluting Stent Implantation. J Clin Med 2021; 10:jcm10163504. [PMID: 34441800 PMCID: PMC8396958 DOI: 10.3390/jcm10163504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/03/2021] [Accepted: 08/06/2021] [Indexed: 11/17/2022] Open
Abstract
We investigated the 2-year efficacy of statin treatment according to baseline renal function in patients with acute myocardial infarction (AMI) not requiring dialysis undergoing newer-generation drug-eluting stent (DES) implantation. A total of 18,875 AMI patients were classified into group A (statin users, n = 16,055) and group B (statin nonusers, n = 2820). According to the baseline estimated glomerular filtration rate (eGFR; ≥90, 60–89, 30–59 and <30 mL/min/1.73 m2), these two groups were sub-classified into groups A1, A2, A3 and A4 and groups B1, B2, B3 and B4. The major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI) and any repeat revascularization, were evaluated. The MACE (group A1 vs. B1, p = 0.002; group A2 vs. B2, p = 0.007; group A3 vs. B3, p < 0.001; group A4 vs. B4, p < 0.001), all-cause death (p = 0.006, p < 0.001, p < 0.001, p < 0.001, respectively) and cardiac death (p = 0.004, p < 0.001, p < 0.001, p < 0.001, respectively) rates were significantly higher in statin nonusers than those in statin users. Despite the beneficial effects of statin treatment, the MACE (group A1 vs. A2 vs. A3 vs. A4: 5.2%, 6.4%, 10.1% and 18.5%, respectively), all-cause mortality (0.9%, 1.8%, 4.6% and 12.9%, respectively) and cardiac death (0.4%, 1.0%, 2.6% and 6.8%, respectively) rates were significantly increased as eGFR decreased in group A. These results may be related to the peculiar characteristics of chronic kidney disease, including increased vascular calcification and traditional or nontraditional cardiovascular risk factors. In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function.
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Noels H, Lehrke M, Vanholder R, Jankowski J. Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations. Nat Rev Nephrol 2021; 17:528-542. [PMID: 33972752 DOI: 10.1038/s41581-021-00423-5] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2021] [Indexed: 02/06/2023]
Abstract
Chronic kidney disease (CKD) induces modifications in lipid and lipoprotein metabolism and homeostasis. These modifications can promote, modulate and/or accelerate CKD and secondary cardiovascular disease (CVD). Lipid and lipoprotein abnormalities - involving triglyceride-rich lipoproteins, LDL and/or HDL - not only involve changes in concentration but also changes in molecular structure, including protein composition, incorporation of small molecules and post-translational modifications. These alterations modify the function of lipoproteins and can trigger pro-inflammatory and pro-atherogenic processes, as well as oxidative stress. Serum fatty acid levels are also often altered in patients with CKD and lead to changes in fatty acid metabolism - a key process in intracellular energy production - that induce mitochondrial dysfunction and cellular damage. These fatty acid changes might not only have a negative impact on the heart, but also contribute to the progression of kidney damage. The presence of these lipoprotein alterations within a biological environment characterized by increased inflammation and oxidative stress, as well as the competing risk of non-atherosclerotic cardiovascular death as kidney function declines, has important therapeutic implications. Additional research is needed to clarify the pathophysiological link between lipid and lipoprotein modifications, and kidney dysfunction, as well as the genesis and/or progression of CVD in patients with kidney disease.
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Affiliation(s)
- Heidi Noels
- Institute for Molecular Cardiovascular Research, RWTH Aachen University, University Hospital, Aachen, Germany
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands
| | - Michael Lehrke
- Department of Internal Medicine I, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Raymond Vanholder
- Nephrology Section, Department of Internal Medicine and Pediatrics, University Hospital, Ghent, Belgium
| | - Joachim Jankowski
- Institute for Molecular Cardiovascular Research, RWTH Aachen University, University Hospital, Aachen, Germany.
- Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, Netherlands.
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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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46
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Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial. J Nephrol 2021; 35:517-525. [PMID: 34173940 DOI: 10.1007/s40620-021-01104-z] [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: 04/16/2021] [Accepted: 06/18/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. METHODS A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. RESULTS Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. CONCLUSIONS In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. TRIAL REGISTRATION NUMBER NCT01457001.
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Kelly DM, Ademi Z, Doehner W, Lip GYH, Mark P, Toyoda K, Wong CX, Sarnak M, Cheung M, Herzog CA, Johansen KL, Reinecke H, Sood MM. Chronic Kidney Disease and Cerebrovascular Disease: Consensus and Guidance From a KDIGO Controversies Conference. Stroke 2021; 52:e328-e346. [PMID: 34078109 DOI: 10.1161/strokeaha.120.029680] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The global health burden of chronic kidney disease is rapidly rising, and chronic kidney disease is an important risk factor for cerebrovascular disease. Proposed underlying mechanisms for this relationship include shared traditional risk factors such as hypertension and diabetes, uremia-related nontraditional risk factors, such as oxidative stress and abnormal calcium-phosphorus metabolism, and dialysis-specific factors such as cerebral hypoperfusion and changes in cardiac structure. Chronic kidney disease frequently complicates routine stroke risk prediction, diagnosis, management, and prevention. It is also associated with worse stroke severity, outcomes and a high burden of silent cerebrovascular disease, and vascular cognitive impairment. Here, we present a summary of the epidemiology, pathophysiology, diagnosis, and treatment of cerebrovascular disease in chronic kidney disease from the Kidney Disease: Improving Global Outcomes Controversies Conference on central and peripheral arterial disease with a focus on knowledge gaps, areas of controversy, and priorities for research.
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Affiliation(s)
- Dearbhla M Kelly
- Wolfson Center for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom (D.M.K.)
| | - Zanfina Ademi
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia (Z.A.)
| | - Wolfram Doehner
- Berlin Institute of Health Center for Regenerative Therapies (BCRT), and Department of Cardiology (Virchow Klinikum), German Centre for Cardiovascular Research (DZHK), Partner Site Berlin and Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Germany (W.D.)
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom (G.Y.H.L.)
| | - Patrick Mark
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, United Kingdom (P.M.)
| | - Kazunori Toyoda
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (K.T.)
| | - Christopher X Wong
- Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia (C.X.W.)
| | - Mark Sarnak
- Division of Nephrology, Tufts Medical Center, Boston, MA (M.S.)
| | - Michael Cheung
- Kidney Disease: Improving Global Outcomes, Brussels, Belgium (M.C.)
| | | | - Kirsten L Johansen
- Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN (K.L.J.)
| | - Holger Reinecke
- Department of Cardiology I, University Hospital Münster, Germany (H.R.)
| | - Manish M Sood
- Ottawa Hospital Research Institute, Department of Medicine, The Ottawa Hospital, Civic Campus, ON, Canada (M.M.S.)
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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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Fazelian S, Moradi F, Agah S, Hoseini A, Heydari H, Morvaridzadeh M, Omidi A, Pizarro AB, Ghafouri A, Heshmati J. Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol 2021; 22:160. [PMID: 33933009 PMCID: PMC8088683 DOI: 10.1186/s12882-021-02351-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 04/12/2021] [Indexed: 11/23/2022] Open
Abstract
Background Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. Methods We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian–Laird’s random-effects model. Results Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95% CI: − 0.51, − 0.02; I2 = 52.7%), TG (SMD: -0.22; 95% CI: − 0.43, − 0.02; I2 = 36.0%) and Malondialdehyde (MDA) levels (SMD: -0.91; 95% CI: − 1.29, − 0.54; I2 = 00.0%) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95% CI: 0.27, 0.90; I2 = 00.0%) and Glutathione peroxidase (GPx) (SMD: 0.50; 95% CI: 0.14, 0.86; I2 = 00.0%) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02351-9.
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Affiliation(s)
- Siavash Fazelian
- Clinical Research Development Unit, Ayatollah Kashani Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Fatemeh Moradi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akramsadat Hoseini
- Department of Education and Health Promotion,School of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hafez Heydari
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Mojgan Morvaridzadeh
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran
| | - Amirhosein Omidi
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran
| | | | - Atie Ghafouri
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Javad Heshmati
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran.
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Zhao L, Li S, Gao Y. Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis. Ren Fail 2021; 43:718-728. [PMID: 33926359 PMCID: PMC8901279 DOI: 10.1080/0886022x.2021.1915799] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background Studies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD. Methods We systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model. Results We selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: −2.04; 95%CI: −3.53 to −0.56; p = .007) and protein (WMD: −0.58; 95%CI: −0.95 to −0.21; p = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32–1.41; p = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: −0.04 to 0.79; p = .075), and serum creatinine levels (WMD: −0.07; 95%CI: −0.25, 0.12; p = .475). Conclusions We found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. Abbreviations: CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate
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Affiliation(s)
- Lin Zhao
- International Medical School, Tianjin Medical University, Tianjin, P.R. China
| | - Shu Li
- School of Public Health, Tianjin Medical University, Tianjin, P.R. China
| | - Ying Gao
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, P.R. China
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