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1
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Cheng FWT, Xu W, Tang SCW, Wan EYF. Long-Term Benefits and Safety of Statins in Patients with Kidney Failure: A Target Trial Emulation Study. J Am Soc Nephrol 2025; 36:882-889. [PMID: 39480503 PMCID: PMC12059101 DOI: 10.1681/asn.0000000554] [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: 06/12/2024] [Accepted: 10/28/2024] [Indexed: 11/02/2024] Open
Abstract
Key Points Patients with kidney failure are at a higher risk of cardiovascular diseases, but the evidence for statin therapy remains inconclusive. The long-term benefits and risks of statin therapy in patients with kidney failure were analyzed using public electronic health records in Hong Kong. Statin therapy was associated with a lower risk of major cardiovascular diseases and all-cause mortality without a higher risk of major adverse events. Background Patients with kidney failure are at elevated risk of cardiovascular diseases. Although statins are commonly used to mitigate cardiovascular risk among the population with high risk, the evidence for initiating statin therapy among patients with kidney failure remains inconclusive. This study aimed to investigate the long-term benefits and risks associated with statin therapy in patients with kidney failure. Methods Using territory-wide public electronic health records in Hong Kong, 3019 statin-eligible individuals with kidney failure and elevated LDL cholesterol ≥100 mg/dl from January 2008 to December 2015 were included for analysis. The framework of target trial emulation was adopted to investigate the risk of the major cardiovascular diseases (i.e ., a composite of myocardial infarction, heart failure, and stroke), all-cause mortality, and major adverse events (i.e ., myopathies and liver dysfunction) between statin initiators and statin noninitiators. The pooled logistic model was used to obtain the hazard ratio for the outcomes of interest in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Results Significant risk reduction associated with statin therapy (hazard ratio [95% confidence interval]) was observed for major cardiovascular diseases (ITT: 0.78 [0.62 to 0.98]; PP: 0.66 [0.50 to 0.87]) and all-cause mortality (ITT: 0.80 [0.68 to 0.95]; PP: 0.60 [0.48 to 0.76]). The standardized 5- and 10-year absolute risk reduction in PP analysis was 7% (3% to 11%) and 11% (4% to 18%), respectively. No significant risks for the major adverse events were observed. Conclusions Statin therapy was associated with lower risks of cardiovascular diseases and all-cause mortality in patients with kidney failure without a higher risk of major adverse events.
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Affiliation(s)
- Franco Wing Tak Cheng
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Pharmacy Department, Gleneagles Hong Kong Hospital, Hong Kong SAR, China
| | - Wanchun Xu
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Sydney Chi Wai Tang
- Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Yuk Fai Wan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D4H), Hong Kong Science and Technology Park, Hong Kong SAR, China
- The Institute of Cardiovascular Science and Medicine (ICSM), Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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2
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Safarova MS, Weintraub S, Sadaniantz K, Kovell L, Warden BA, Garshick MS, Duell PB, Gianos E. Statin Use in Special Populations for the Prevention of Cardiovascular Disease in Adults. Curr Atheroscler Rep 2025; 27:54. [PMID: 40310600 DOI: 10.1007/s11883-025-01298-8] [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] [Accepted: 04/06/2025] [Indexed: 05/02/2025]
Abstract
PURPOSE OF REVIEW Outcome benefits for HMG-CoA reductase inhibitor (statin) use in the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established and yet, statins remain underutilized with only half of eligible individuals receiving them among certain vulnerable populations. This review critically examines available data to provide a summary of the current evidence for statin use in select populations. RECENT FINDINGS Lipid management can be more complex in patients with chronic kidney disease (CKD), organ transplants, metabolic dysfunction associated with steatotic liver disease (MASLD), and human immunodeficiency virus (HIV). Statins are generally safe and effective to reduce the burden of ASCVD among these highly heterogeneous groups of patients and should be considered with careful attention to their concomitant disease state. Herein, we focus on appropriate statin use in these challenging to treat conditions, their relationship with increased ASCVD risk, and approaches to statin use for ASCVD risk reduction. Although further research is needed to define optimal therapy in select high risk groups for ASCVD prevention, statins are proven to be clinically efficacious, safe, and cost-effective for ASCVD prevention, warranting greater efforts to increase their use.
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Affiliation(s)
- Maya S Safarova
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Spencer Weintraub
- Northwell Cardiovascular Institute, North Shore University Hospital, Manhasset, NY, USA
| | - Katherine Sadaniantz
- Department of Medicine, Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Lara Kovell
- Department of Medicine, Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Bruce A Warden
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
| | - Michael S Garshick
- Division of Cardiology, Department of Medicine and Department of Dermatology, NYU Langone Health, New York, NY, USA
| | - P Barton Duell
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
- Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health & Science University, Portland, OR, USA
| | - Eugenia Gianos
- Northwell Cardiovascular Institute, Lenox Hill Hospital, New York, NY, USA
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3
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Kowalczyk NS, Prochaska M. Mitigating heart failure risk in patients with diabetes and chronic kidney disease. Curr Opin Cardiol 2025; 40:178-183. [PMID: 39998480 DOI: 10.1097/hco.0000000000001208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
PURPOSE OF REVIEW Patients with chronic kidney disease and diabetes are at high risk of cardiovascular disease, including heart failure. Risk mitigation requires a comprehensive approach with lifestyle modifications, blood pressure management, renin-angiotensin blockade, and sodium-glucose cotransporter 2 inhibitors. Recent trials have shown that nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) should also be components of this approach. This review will discuss the comprehensive approach to mitigating risk in these high-risk patients and highlight the recent trials of ns-MRAs and GLP-1 RA. RECENT FINDINGS In recent years, large, randomized controlled trials of ns-MRA and GLP-1 RA have shown benefit in kidney and cardiovascular outcomes for patients with chronic kidney disease and diabetes. SUMMARY The substantial benefits and overall favorable safety profiles for ns-MRA and GLP-1 RA in patients with chronic kidney disease and diabetes demonstrate that these medications should be considered as a part of a comprehensive approach to cardiovascular risk reduction in this high-risk population. Future studies should consider different combination therapies and guide how and when to initiate these therapies.
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Weltman MR, Lavenburg LMU, Han Z, Alghwiri AA, Mosslemi M, Rollman BL, Fischer GS, Nolin TD, Yabes JG, Jhamb M. Population Health Management and Guideline-Concordant Care in CKD: A Secondary Analysis of Kidney Coordinated HeAlth Management Partnership. J Am Soc Nephrol 2025; 36:869-881. [PMID: 39485493 PMCID: PMC12059108 DOI: 10.1681/asn.0000000544] [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: 04/03/2024] [Accepted: 10/28/2024] [Indexed: 11/03/2024] Open
Abstract
Key Points Implementation gaps in guideline-concordant care for CKD are associated with poor clinical outcomes. A population health management–based, multidisciplinary approach improved exposure days to sodium-glucose cotransporter-2 inhibitor and glucagon-like peptide-1 receptor agonists compared with usual care. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in albuminuric patients and statin use was not improved, nor was BP control, glycemic control, or albuminuria testing. Background Gaps in guideline-concordant care for CKD lead to poor outcomes. The Kidney Coordinated HeAlth Management Partnership (K-CHAMP) cluster randomized trial tested the effect of a population health management intervention versus usual care on CKD progression and evidence-based care delivery in the primary care setting. Methods K-CHAMP included adults aged 18–85 years with eGFR<60 ml/min per 1.73 m2 and moderate-high risk of CKD progression who were not seeing a nephrologist. The multifaceted intervention included nephrology e-consult, pharmacist-led medication management, and patient education. In this post hoc analysis, we evaluate the effectiveness of K-CHAMP on guideline-concordant care processes (BP and glycemic control, annual albuminuria testing) and medication exposure days (angiotensin-converting enzyme inhibitor [ACEi]/angiotensin receptor blocker [ARB], moderate-high intensity statin, sodium-glucose cotransporter-2 inhibitor [SGLT2i], glucagon-like peptide-1 receptor agonists [GLP-1RA]). Given multiplicity of outcomes, Benjamini–Hochberg method was used to control false discovery rate. Results All 1596 (754 intervention, 842 usual care) enrolled patients (mean age 74±9 years, eGFR 37±8 ml/min per 1.73 m2, 928 [58%] female, 127 [8%] Black) were analyzed. After a median 17-month follow-up, intervention arm patients had significantly higher exposure days per year to SGLT2i (56 versus 32 days; relative benefit 1.72; 95% confidence interval [CI], 1.14 to 2.30) and GLP-1RA (78 versus 29 days; relative benefit 2.65; 95% CI, 1.59 to 3.71) compared with usual care in adjusted analysis. At study initiation in 2019, similar proportion of patients were prescribed SGLT2i and/or GLP-1RA in intervention and control arm (8% versus 6%, respectively; rate ratio 1.23; 95% CI, 0 to 2.99), but by 2022, prescription of these medications was significantly higher in intervention arm (44% versus 27%, respectively; rate ratio 1.63; 95% CI, 1.32 to 1.94). There was no significant difference in any process measures or exposure days to ACEi/ARB in patients with albuminuria or moderate-high intensity statin. Conclusions K-CHAMP was effective in accelerating implementation of SGLT2i and GLP-1RA but did not increase ACEi/ARB in patients with albuminuria or moderate-high intensity statin use or improve BP control, glycemic control, or albuminuria testing in individuals with CKD in the primary care setting. Clinical Trial registry name and registration number: K-CHAMP, NCT03832595 .
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Affiliation(s)
- Melanie R. Weltman
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania
| | - Linda-Marie U. Lavenburg
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Zhuoheng Han
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Alaa A. Alghwiri
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Mitra Mosslemi
- Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
| | - Bruce L. Rollman
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Center for Behavioral Health, Media, and Technology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Gary S. Fischer
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Thomas D. Nolin
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania
| | - Jonathan G. Yabes
- Division of General Internal Medicine, Department of Medicine and Biostatistics, Center for Research on Heath Care, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Manisha Jhamb
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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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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Iyalomhe OE, Saparamadu AADNS, Alexander GC. Use of Statins for Primary Prevention Among Individuals With CKD in the United States: A Cross-Sectional, Time-Trend Analysis. Am J Kidney Dis 2025; 85:421-431.e1. [PMID: 39743168 DOI: 10.1053/j.ajkd.2024.11.003] [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: 07/23/2024] [Revised: 10/06/2024] [Accepted: 11/18/2024] [Indexed: 01/04/2025]
Abstract
RATIONALE & OBJECTIVE Chronic kidney disease (CKD) populations face an elevated risk of cardiovascular disease (CVD), yet many remain undertreated with statins for primary prevention of CVD despite meeting eligibility criteria. We examined trends in statin use for primary prevention among individuals with CKD before and after the release of the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommending statin use for lipid management in selected adults with CKD. STUDY DESIGN Cross-sectional time-trend analysis. SETTING & PARTICIPANTS The 2001-2020 National Health and Nutrition Examination Survey (NHANES) data permitted identification of individuals eligible for statin therapy per the 2013 KDIGO guidelines based on (1) age≥50 without self-reported CVD; (2) CKD, defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 or albumin-creatinine ratio≥30mg/g; and (3) no dialysis in the previous 12 months. OUTCOME Statin use. ANALYTICAL APPROACH Poisson regression to estimate prevalence ratios (PR) comparing the periods before and after KDIGO guideline release and after accounting for NHANES's complex survey design and sampling weights. RESULTS Among eligible individuals, statin use approximately doubled from 18.6% in 2001-2002 to 36.1% in 2007-2008, increased modestly to 40.1% in 2013-2014, then subsequently plateaued. Multivariable analyses controlling for sociodemographic and clinical characteristics and secular trends demonstrated statin use for primary prevention was higher among the insured (PR, 2.48 [95% CI 1.66-3.69]), those with hypertension (PR, 1.49 [95% CI 1.28-1.74]), and those with diabetes (PR, 1.71 [95% CI 1.52-1.92]). Statin use was more common with lower eGFR (P=0.009) and higher body mass index (P=0.003) but did not differ by sex, race, or ethnicity. LIMITATIONS Statin use and CVD were self-reported, and our data did not capture statin intolerance nor patient-provider decision making information. CONCLUSIONS Statin use for primary prevention in CKD substantially increased before the 2013 release of KDIGO guidelines and subsequently plateaued. Use was higher among the insured and those with hypertension or diabetes. PLAIN-LANGUAGE SUMMARY Chronic kidney disease (CKD) affects many Americans, increasing their heart disease risk. Statins effectively reduce this risk in individuals with CKD but are underused. Our study examined statin use in individuals with CKD before and after the release of the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommending statin use for selected adults with CKD. It also examined factors influencing usage patterns. Using years of US National Health and Nutrition Examination Survey data, we found that while statin use doubled over the study period, fewer than half of eligible individuals with CKD received statins for primary prevention. Statin use was more common among those with health insurance, high blood pressure, or diabetes. This underuse highlights potential opportunities for improved risk monitoring and preventive use of statin therapy for individuals with CKD.
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Affiliation(s)
- Oshozimhede E Iyalomhe
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | | | - G Caleb Alexander
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Division of General Internal Medicine, Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland.
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7
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Bahl A, Prasad N, Sinha DP, Ganguly K, Roy S, Roy D, Rakshit S, Kumar D, Das S, Bhasin D, Raju SB, Trivedi M, Rathi M, Gulati S, Agstam S, Bhargava V, Bhalla AK, Bansal SB, Varughese S, Patel MR, Yadav R, Naik N, Bang VH, Dastidar DG, Banerjee PS. Cardiac evaluation in patients awaiting kidney transplant-position statement of the Cardiological Society of India and Indian Society of Nephrology. Indian Heart J 2025:S0019-4832(25)00058-6. [PMID: 40147817 DOI: 10.1016/j.ihj.2025.03.012] [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: 01/03/2024] [Revised: 06/25/2024] [Accepted: 03/25/2025] [Indexed: 03/29/2025] Open
Abstract
Cardiovascular diseases are a major cause of death after kidney transplantation. This statement addresses preoperative cardiac decision-making and management with the aim of assessing and reducing the risk of the kidney transplant surgery. Important issues from a clinician's perspective include the basic cardiovascular workup of these patients, coronary evaluation and management of coronary artery disease, valvular heart disease and left ventricular systolic dysfunction. Recovery left ventricular function after kidney transplant is discussed. In addition, the use of cardiovascular drugs in patients with special emphasis on antiplatelets and anticoagulants in patients planned for kidney transplant is also discussed.
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Affiliation(s)
- Ajay Bahl
- Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | | | | | - Debabrata Roy
- Department of Cardiology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India
| | - Sumit Rakshit
- Department of Cardiology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India
| | - Dilip Kumar
- Medica Superspeciality Hospital, Kolkata, India
| | - Saurav Das
- Medica Superspeciality Hospital, Kolkata, India
| | - Dinkar Bhasin
- Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sree Bhushan Raju
- Dept of Nephrology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Mayuri Trivedi
- Department of Nephrology, Lokmanya Tilak Municipal General Hospital, Mumbai, India
| | - Manish Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjeev Gulati
- Principal Director, Nephrology and Transplantation, Fortis Group Hospitals, New Delhi, India
| | - Sourabh Agstam
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Vinant Bhargava
- Department of Nephrology, Sir Gangaram Hospital, New Delhi, India
| | | | | | | | - Manas Ranjan Patel
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Yadav
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Nitish Naik
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Partha Sarathi Banerjee
- Chief Interventional Cardiologist, Manipal Hospital, Kolkata, Former Head, Department of Cardiology, Medical College, Kolkata, India
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Beaudrey T, Bedo D, Weschler C, Caillard S, Florens N. From Risk Assessment to Management: Cardiovascular Complications in Pre- and Post-Kidney Transplant Recipients: A Narrative Review. Diagnostics (Basel) 2025; 15:802. [PMID: 40218153 PMCID: PMC11988545 DOI: 10.3390/diagnostics15070802] [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: 02/14/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.
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Affiliation(s)
- Thomas Beaudrey
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Dimitri Bedo
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Célia Weschler
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
| | - Sophie Caillard
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, 67000 Strasbourg, France
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9
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Tramontano D, Bini S, Maiorca C, Di Costanzo A, Carosi M, Castellese J, Arizaj I, Commodari D, Covino S, Sansone G, Minicocci I, Arca M, D'Erasmo L. Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions. Drugs 2025:10.1007/s40265-025-02158-0. [PMID: 40106181 DOI: 10.1007/s40265-025-02158-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2025] [Indexed: 03/22/2025]
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.
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Affiliation(s)
- Daniele Tramontano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
| | - Simone Bini
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Carlo Maiorca
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessia Di Costanzo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Martina Carosi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jacopo Castellese
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ina Arizaj
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniela Commodari
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Stella Covino
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giorgia Sansone
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ilenia Minicocci
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Marcello Arca
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Laura D'Erasmo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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10
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Prabhahar A, Batta A, Hatwal J, Kumar V, Ramachandran R, Batta A. Endothelial dysfunction in the kidney transplant population: Current evidence and management strategies. World J Transplant 2025; 15:97458. [PMID: 40104196 PMCID: PMC11612885 DOI: 10.5500/wjt.v15.i1.97458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 09/04/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024] Open
Abstract
The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators. Endothelial dysfunction (ED), characterized by impaired vasodilation, inflammation, and thrombosis, triggers future cardiovascular (CV) diseases. Chronic kidney disease, a state of chronic inflammation caused by oxidative stress, metabolic abnormalities, infection, and uremic toxins damages the endothelium. ED is also associated with a decline in estimated glomerular filtration rate. After kidney transplantation, endothelial functions undergo immediate but partial restoration, promising graft longevity and enhanced CV health. However, the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED, culminating in poor CV health and graft survival. ED in kidney transplant recipients is an under-recognized and poorly studied entity. CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts. ED contributes to the pathogenesis of many of the CV diseases. Various biomarkers and vasoreactivity tests are available to study endothelial functions. With an increasing number of transplants happening every year, and improved graft rejection rates due to the availability of effective immunosuppressants, the focus has now shifted to endothelial protection for the prevention, early recognition, and treatment of CV diseases.
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Affiliation(s)
- Arun Prabhahar
- Department of Telemedicine (Internal Medicine and Nephrology), Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akshey Batta
- Department of Urology and Renal Transplant, Neelam Hospital, Rajpura 140401, Punjab, India
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Vivek Kumar
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Raja Ramachandran
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
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11
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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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12
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Concannon K, Bentz Z, Kokosa S, Berry H, Byrns J. Evaluation of lipid management practices for secondary atherosclerotic cardiovascular disease prevention in abdominal solid organ transplant recipients. J Clin Lipidol 2025:S1933-2874(25)00023-6. [PMID: 40157862 DOI: 10.1016/j.jacl.2025.02.004] [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: 09/15/2024] [Revised: 01/07/2025] [Accepted: 02/04/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND High-intensity HMG-CoA reductase inhibitors (statins) are recommended for secondary atherosclerotic cardiovascular disease (ASCVD) prevention. Solid organ transplant (SOT) recipients are at an increased risk of ASCVD events. This study evaluated if abdominal SOT recipients who experienced an ASCVD event prior to transplant received guideline-directed pharmacotherapy for secondary ASCVD prevention post-transplant. METHODS Single-center, retrospective, cohort study that evaluated lipid-lowering therapy prescribing practices in SOT recipients transplanted at Duke University Hospital. The primary objective was the percentage of patients receiving a high-intensity statin regimen during the first year post-transplant. Secondary objectives included reason for change in statin therapy, other lipid-lowering medications prescribed, percentage of patients who had lipid panel(s) drawn, safety of statin therapy, and the incidence of recurrent ASCVD or death secondary to an ASCVD event within the first year post-transplant. RESULTS Sixty-three transplant patients were included, 46 (73%) received a kidney, 12 (19%) a liver, and 5 (7.9%) a multi-organ transplant. Twenty-four patients (38.1%) were maintained on a high-intensity statin during the first year post-transplant. Reason for statin dose change included elevated lipids (35.3%), statin-related safety event (11.8%), and undocumented reason (52.9%). Statins were well tolerated. Two (3.2%) patients experienced a recurrent myocardial infarction within the first year post-transplant. CONCLUSION Less than half of the abdominal transplant patients were maintained on guideline-directed high-intensity statin therapy for secondary ASCVD prevention at 1 year post-transplant. Our findings demonstrate an opportunity to optimize the prescribing practices of lipid-lowering therapy following abdominal transplant in a high cardiovascular risk population.
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Affiliation(s)
- Kennedy Concannon
- Department of Pharmacy, University of Colorado Anschutz Medical Center, Aurora CO, USA (Dr Concannon)
| | - Zachary Bentz
- Department of Pharmacy, Carilion Clinic Roanoke Memorial Hospital, Roanoke VA, USA (Dr Bentz)
| | - Sarah Kokosa
- Department of Pharmacy, Duke University Hospital, Durham NC, USA (Drs Kokosa and Byrns)
| | - Holly Berry
- Department of Pharmacy, Durham Veterans Affairs Medical Center, Durham NC, USA (Dr Berry)
| | - Jennifer Byrns
- Department of Pharmacy, Duke University Hospital, Durham NC, USA (Drs Kokosa and Byrns).
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13
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Park Y, Hwang WM. Management of Elderly Patients with Chronic Kidney Disease. Yonsei Med J 2025; 66:63-74. [PMID: 39894039 PMCID: PMC11790406 DOI: 10.3349/ymj.2024.0178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/23/2024] [Accepted: 10/08/2024] [Indexed: 02/04/2025] Open
Abstract
Chronic kidney disease (CKD) is highly prevalent among elderly patients, and as the global population ages, the number of elderly patients with CKD is increasing. Elderly patients require additional considerations beyond those required for their younger counterparts, such as comorbidities, frailty, and geriatric syndromes. In this review, we primarily focus on these additional considerations specific to elderly patients and discuss the assessment of CKD and its management strategies, including blood pressure and glycemic control; dyslipidemia, anemia, and electrolyte and metabolic acidosis management; and medication dosage, among others, as well as polypharmacy and nonpharmacological management. Furthermore, the concept of conservative kidney management and the practical recommendations of the Korean Society of Geriatric Nephrology for elderly patients with end-stage kidney disease requiring dialysis therapy are discussed. In particular, the aging rate in Korea is exceptionally high; therefore, it is crucial to pay more attention to the increase in elderly patients with CKD. A more palliative approach, rather than intensive treatment strategies, may be necessary for these patients. In a world with an abundance of information, shared decision-making with patients is of great importance, and it is essential to keep in mind that this holds true for elderly patients as well.
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Affiliation(s)
- Yohan Park
- Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, Korea
| | - Won Min Hwang
- Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, Korea.
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14
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Bolignano D, Simeoni M, Hafez G, Pepin M, Gallo A, Altieri M, Liabeuf S, Giannakou K, De A, Capasso G. Cognitive impairment in CKD patients: a guidance document by the CONNECT network. Clin Kidney J 2025; 18:sfae294. [PMID: 40235626 PMCID: PMC11997768 DOI: 10.1093/ckj/sfae294] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Indexed: 04/17/2025] Open
Abstract
Cognitive impairment is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). This position paper, developed by the Cognitive Decline in Nephro-Neurology: European Cooperative Target network, provides guidance on the epidemiology, risk factors, pathophysiology, diagnosis and clinical management of CKD-related cognitive impairment. Cognitive impairment is significantly more common in CKD patients compared with the general population, particularly those undergoing haemodialysis. The development of cognitive impairment is influenced by a complex interplay of factors, including uraemic neurotoxins, electrolytes and acid-base disorders, anaemia, vascular damage, metabolic disturbances and comorbidities like diabetes and hypertension. Effective screening and diagnostic strategies are essential for early identification of cognitive impairment utilizing cognitive assessment tools, neuroimaging and circulating biomarkers. The impact of various drug classes, including antiplatelet therapy, oral anticoagulants, lipid-lowering treatments and antihypertensive drugs, on cognitive function is evaluated. Management strategies encompass pharmacological and non-pharmacological interventions, with recommendations for optimizing cognitive function while managing CKD-related complications. This guidance highlights the importance of addressing cognitive impairment in CKD patients through early detection, careful medication management and tailored therapeutic strategies to improve patient outcomes.
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Affiliation(s)
- Davide Bolignano
- Department of Medical and Surgical Sciences, “Magna-Graecia” University of Catanzaro, Catanzaro, Italy
| | - Mariadelina Simeoni
- Division of Nephrology and Dialysis, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Gaye Hafez
- Department of Pharmacology, Faculty of Pharmacy, Altinbas University, Istanbul, Turkey
| | - Marion Pepin
- Ambroise Paré University Hospital, APHP, Geriatric Department, Versailles St Quentin University, Boulogne Billancourt, France
- Inserm Unit 1018, CESP, Clinical Epidemiology Team, Paris Saclay University, Villejuif, France
| | - Antonio Gallo
- I Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Manuela Altieri
- I Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Sophie Liabeuf
- Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France
- MP3CV Laboratory, EA7517, Jules Verne University of Picardie, Amiens, France
| | - Konstantinos Giannakou
- Department of Health Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - Ananya De
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
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15
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Zitnik E, Streja E, Laster M. The Impact of Glomerular Disease on Dyslipidemia in Pediatric Patients Treated with Dialysis. Nutrients 2025; 17:459. [PMID: 39940317 PMCID: PMC11819668 DOI: 10.3390/nu17030459] [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: 12/26/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES Children on dialysis have a 10-fold increase in cardiovascular disease (CVD)-related mortality when compared to the general population. The development of CVD in dialysis patients is attributed to Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) and dyslipidemia. While the prevalence of dyslipidemia in adult dialysis patients has been described, there are limited data on prevalence, severity, and risk factors for pediatric dyslipidemia. METHODS Data from 1730 pediatric patients ≤ 21 years receiving maintenance hemodialysis or peritoneal dialysis with at least one lipid panel measurement were obtained from USRDS between 2001 and 2016. Disease etiology was classified as being glomerular (n = 1029) or non-glomerular (n = 701). Comparisons were made across etiologies using both linear and logistic regression models to determine the relationship between disease etiology and lipid levels. RESULTS The cohort had a mean age of 15.2 years and were 54.5% female. Adjusting for age, sex, race/ethnicity, modality, time with End Stage Kidney Disease (ESKD), and body mass index (BMI) and using non-glomerular etiology as the reference, glomerular disease [mean (95% CI)] was associated with +19% (+14.7%, +23.8%) higher total cholesterol level (183 mg/dL vs. 162 mg/dL), +21% (+14.8%, +26.6%) higher low density lipoprotein cholesterol level (108 mg/dL vs. 87 mg/dL), and +22.3% (+15.5%, +29.5%) higher triglyceride level (169 mg/dL vs. 147 mg/dL). Glomerular disease [OR (95% CI)] was associated with 3.0-fold [2.4, 3.9] higher odds of having an abnormal total cholesterol level, 3.8-fold [2.8, 5.0] higher odds of having an abnormal LDL-C level, and 1.9-fold [1.5, 2.4] higher odds of having an abnormal triglyceride level when compared to non-glomerular disease. CONCLUSIONS Pediatric dialysis patients have a high prevalence of dyslipidemia, particularly from elevated triglyceride levels. Specifically, patients with glomerular disease have an even higher risk of dyslipidemia from elevated non-HDL cholesterol and triglyceride levels than patients with non-glomerular disease. The long-term impact of this unfavorable lipid profile requires further investigation.
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Affiliation(s)
- Edward Zitnik
- Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06032, USA
| | - Elani Streja
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA;
| | - Marciana Laster
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
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16
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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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17
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Shin D, Galougahi KK, Singh M, Caron E, Cannata M, Ciftcikal Y, Gujja M, Sakai K, Moses J, Shlofmitz R, Al-Azizi K, Doshi D, Jeremias A, Shlofmitz E, Ali ZA. Coronary artery disease and percutaneous coronary intervention in patients with severe chronic kidney disease. Prog Cardiovasc Dis 2025; 88:75-79. [PMID: 39761789 DOI: 10.1016/j.pcad.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Accepted: 12/28/2024] [Indexed: 01/13/2025]
Abstract
Coronary artery disease (CAD) is the leading cause of mortality among patients with chronic kidney disease (CKD), presenting unique challenges in diagnosis and management. Advanced CKD patients often present with atypical symptoms, and conventional diagnostic and interventional approaches carry risks, including contrast-induced nephropathy and the potential need for renal replacement therapy. These risks have led to the phenomenon of "renalism," where necessary procedures may be deferred due to concerns over renal injury. Emerging techniques, such as ultra-low contrast angiography (ULCA) and zero-contrast percutaneous coronary intervention (PCI), offer promising solutions by minimizing or eliminating contrast exposure. This review discusses the clinical presentation of CAD in CKD patients, limitations of traditional diagnostic approaches, and the challenges in managing these high-risk patients. It also provides an overview of ULCA and zero-contrast PCI techniques, which have shown both safety and feasibility even in complex cases. As these techniques continue to evolve, zero-contrast PCI holds the potential to become an essential component of revascularization strategies for high-risk CKD patients, enhancing procedural safety while maintaining therapeutic efficacy.
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Affiliation(s)
- Doosup Shin
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | | | - Mandeep Singh
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA; New York Institute of Technology, Old Westbury, New York, USA
| | - Emma Caron
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Matthew Cannata
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Yasemin Ciftcikal
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Misha Gujja
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Koshiro Sakai
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Jeffrey Moses
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Richard Shlofmitz
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Karim Al-Azizi
- Baylor Scott & White The Heart Hospital - Plano, Plano, Texas, United States of America
| | - Darshan Doshi
- Massachusetts General Hospital, Boston, MA, United States of America
| | - Allen Jeremias
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Evan Shlofmitz
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA
| | - Ziad A Ali
- Department of Cardiology, St Francis Hospital and Heart Center, Roslyn, New York, USA; New York Institute of Technology, Old Westbury, New York, USA.
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18
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Kim JJ, Yang EJ, Molina David J, Cho S, Ficarella M, Pape N, Schiffer JE, Njeim R, Kim SS, Lo Re C, Fontanella A, Kaber M, Sloan A, Merscher S, Fornoni A. Ezetimibe Enhances Lipid Droplet and Mitochondria Contact Formation, Improving Fatty Acid Transfer and Reducing Lipotoxicity in Alport Syndrome Podocytes. Int J Mol Sci 2024; 25:13134. [PMID: 39684843 DOI: 10.3390/ijms252313134] [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: 10/29/2024] [Revised: 11/28/2024] [Accepted: 12/03/2024] [Indexed: 12/18/2024] Open
Abstract
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alport syndrome (AS), contributing to podocyte injury and disease progression. Ezetimibe, a lipid-lowering drug, is known to inhibit cholesterol and fatty acid uptake and to reduce triglyceride content in the kidney cortex of mice with AS. However, its effects on lipid droplet (LD) utilization by mitochondria have not been explored. Transmission electron microscopy (TEM) and mitochondrial functional assays (ATP production, mitochondrial membrane potential, and citrate synthase activity) were used to investigate the impact of ezetimibe on LD-mitochondria contact formation and mitochondrial function in Col4a3KO (AS) and wildtype (WT) podocytes. TEM analysis revealed significant mitochondrial abnormalities in AS podocytes, including swollen mitochondria and reduced cristae density, while mitochondrial function assays showed decreased ATP production and lowered mitochondrial membrane potential. AS podocytes also demonstrated a higher content of LD but with reduced LD-mitochondria contact sites. Ezetimibe treatment significantly increased the number of LD-mitochondria contact sites, enhanced fatty acid transfer efficiency, and reduced intracellular lipid accumulation. These changes were associated with a marked reduction in the markers of lipotoxicity, such as apoptosis and oxidative stress. Mitochondrial function was significantly improved, evidenced by increased basal respiration, ATP production, maximal respiration capacity, and the restoration of mitochondrial membrane potential. Additionally, mitochondrial swelling was significantly reduced in ezetimibe-treated AS podocytes. Our findings reveal a novel role for ezetimibe in enhancing LD-mitochondria contact formation, leading to more efficient fatty acid transfer, reduced lipotoxicity, and improved mitochondrial function in AS podocytes. These results suggest that ezetimibe could be a promising therapeutic agent for treating mitochondrial dysfunction and lipid metabolism abnormalities in AS.
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Affiliation(s)
- Jin-Ju Kim
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Eun-Jeong Yang
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Judith Molina David
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Sunjoo Cho
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Maria Ficarella
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Nils Pape
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Josephin Elizabeth Schiffer
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Rachel Njeim
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Stephanie S Kim
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Claudia Lo Re
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, A.O.U "G. Martino", University of Messina, 98122 Messina, Italy
| | - Antonio Fontanella
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Maria Kaber
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Alexis Sloan
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Sandra Merscher
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Alessia Fornoni
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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19
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Yen CL, Fan PC, Lee CC, Chen JJ, Chen CY, Tu YR, Chu PH, Hsiao CC, Chen YC, Chang CH. The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients. Atherosclerosis 2024; 399:119042. [PMID: 39531896 DOI: 10.1016/j.atherosclerosis.2024.119042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/29/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIMS Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. METHODS By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. RESULTS At 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69-0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65-0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54-0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80-0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. CONCLUSIONS Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.
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Affiliation(s)
- Chieh-Li Yen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Chun Fan
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Chia Lee
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jia-Jin Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chao-Yu Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Ran Tu
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pao-Hsien Chu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Ching-Chung Hsiao
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yung-Chang Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Hsiang Chang
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medicine Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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20
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Abdullah, Zaheer A, Saeed H, Arshad MK, Zabeehullah, Iftikhar U, Abid A, Khan MH, Khan AS, Akbar A. Managing Dyslipidemia in Children: Current Approaches and the Potential of Artificial Intelligence. Cardiol Rev 2024:00045415-990000000-00372. [PMID: 39601582 DOI: 10.1097/crd.0000000000000816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Dyslipidemia is abnormal lipid and lipoprotein levels in the blood, influenced mainly by genetics, lifestyle, and environmental factors. The management of lipid levels in children involves early screening, nonpharmacological interventions such as lifestyle modifications and dietary changes, nutraceuticals, and pharmacological treatments, including drug therapy. However, the prevalence of dyslipidemia in the pediatric population is increasing, particularly among obese children, which is a significant risk factor for cardiovascular complications. This narrative review analyzes current literature on the management of dyslipidemia in children and explores the potential of artificial intelligence (AI) to improve screening, diagnosis, and treatment outcomes. A comprehensive literature search was conducted using Google Scholar and PubMed databases, focusing primarily on the application of AI in managing dyslipidemia. AI has been beneficial in managing lipid disorders, including lipid profile analysis, obesity assessments, and familial hypercholesterolemia screening. Deep learning models, machine learning algorithms, and artificial neural networks have improved diagnostic accuracy and treatment efficacy. While most studies are done in the adult population, the promising results suggest further exploring AI management of dyslipidemia in children.
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Affiliation(s)
- Abdullah
- Department of Medicine, Rawalpindi Medical University, Rawalpindi
| | - Amna Zaheer
- Department of Medicine, Liaquat National Hospital and Medical College, Karachi
| | - Humza Saeed
- Department of Medicine, Rawalpindi Medical University, Rawalpindi
| | | | - Zabeehullah
- Department of Medicine, Rawalpindi Medical University, Rawalpindi
| | - Uswa Iftikhar
- Department of Medicine, Rawalpindi Medical University, Rawalpindi
| | - Areesha Abid
- Department of Medicine, Rawalpindi Medical University, Rawalpindi
| | - Muhammad Hamza Khan
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Alina Sami Khan
- Department of Medicine, Liaquat National Hospital and Medical College, Karachi
| | - Anum Akbar
- Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE
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21
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Spasovski G, Markovska ZS, Gjorgjievski N, Poposka L, Kostov J, Bosevski M, Ahmeti I, Jovanovska-Mishevska S, Milenkovic T. Diabetic Kidney Disease Position Paper of the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO), Macedonian Society of Cardiology (MSC), and Scientific Association of Endocrinologists and Diabetologists of Macedonia (SAEDM). Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2024; 45:107-116. [PMID: 39667008 DOI: 10.2478/prilozi-2024-0027] [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: 12/14/2024]
Abstract
Diabetic kidney disease (DKD) is a significant and growing global health concern, affecting a substantial proportion of individuals with diabetes mellitus. This position paper of Scientific societies of endocrinologists, nephrologists and cardiologists has been consensually brought at a couple of mutual meetings, aiming to synthesize current knowledge on screening, diagnosis and staging of DKD, emphasizing the need for an early detection and intervention in order to prevent progression to end-stage renal disease (ESRD). The role of glycemic control, blood pressure management, lipid management and the use of reno and cardioprotective agents, including angiotensin-converting enzyme inhibitors, sodium-glucose co-transporter 2 inhibitors and non-steroidal mineralocorticisteroid receptor antagonist has been entirely considered. Furthermore, we highlight the importance of a multidisciplinary approach in the care of patients with DKD, integrating lifestyle modifications and patient education into the clinical practice. This paper advocates for the implementation of standardized screening protocols and the development of personalized treatment strategies to optimize patient outcomes. By addressing the complexities of DKD, we aim to provide a comprehensive framework for healthcare professionals to enhance the quality of care for individuals at risk of or living with this condition.
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Affiliation(s)
- Goce Spasovski
- University Department of Nephrology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Zaklina Sterjova Markovska
- University Department of Nephrology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Nikola Gjorgjievski
- University Department of Nephrology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Lidija Poposka
- University Department of Cardiology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Jorgo Kostov
- University Department of Cardiology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Marijan Bosevski
- University Department of Cardiology, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Irfan Ahmeti
- University Department of Endocrinology and metabolic disease, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Sasha Jovanovska-Mishevska
- University Department of Endocrinology and metabolic disease, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
| | - Tatjana Milenkovic
- University Department of Endocrinology and metabolic disease, Medical Faculty, Sts Cyril and Methodius University in Skopje, RN Macedonia
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22
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Letts M, Chesnaye NC, Pippias M, Caskey F, Jager KJ, Dekker FW, van Diepen M, Evans M, Torino C, Vilasi A, Szymczak M, Drechsler C, Wanner C, Hole B, Hayward S. Prescribing patterns in older people with advanced chronic kidney disease towards the end of life. Clin Kidney J 2024; 17:sfae301. [PMID: 39669395 PMCID: PMC11635369 DOI: 10.1093/ckj/sfae301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Indexed: 12/14/2024] Open
Abstract
Background Advancing age and chronic kidney disease (CKD) are risk factors for polypharmacy. Polypharmacy is associated with negative healthcare outcomes. Deprescribing, the systematic rationalization of potentially inappropriate medications, is a proposed way of addressing polypharmacy. The aim of this study was to describe longitudinal prescribing patterns of oral medications in a cohort of older people with advanced CKD in their last years of life. Methods The European QUALity (EQUAL) study is a European, prospective cohort study of people ≥65 years with an incident estimated glomerular filtration rate (eGFR) of ≤20 mL/min/1.73 m2. We analysed a decedent subcohort, using generalized additive models to explore trends in the number and types of prescribed oral medications over the years preceding death. Results Data from 563 participants were analysed (comprising 2793 study visits) with a median follow-up time of 2.2 years (interquartile range 1.1-3.8) pre-death. Participants' numbers of prescribed oral medications increased steadily over the years approaching death-7.3 (95% confidence interval 6.9-7.7) 5 years pre-death and 8.7 (95% confidence interval 8.4-9.0) at death. Over the years pre-death, the proportion of people prescribed (i) proton-pump inhibitors and opiates increased and (ii) statins, calcium-channel blockers and renin-angiotensin-aldosterone system inhibitors decreased, whilst (iii) beta-blockers, diuretics and gabapentinoids remained stable. At their final visits pre-death 14.6% and 5.1% were prescribed opiates and gabapentinoids, respectively. Conclusion Elderly people with advanced CKD experienced persistent and increasing levels of polypharmacy as they approached the end of life. There was evidence of cessation of certain classes of medications, but at a population level this was outweighed by new prescriptions. This work highlights the potential for improved medication review in this setting to reduce the risks associated with polypharmacy. Future work should focus at the individual patient-clinician level to better understand the decision-making process underlying the observed prescribing patterns.
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Affiliation(s)
- Matthew Letts
- Population health sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Nicholas C Chesnaye
- ERA registry, Department of Medical Informatics, Amsterdam UMC, location Academical Medical Center, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, The Netherlands
| | - Maria Pippias
- Population health sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Fergus Caskey
- Population health sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Kitty J Jager
- ERA registry, Department of Medical Informatics, Amsterdam UMC, location Academical Medical Center, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, The Netherlands
| | - Friedo W Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Merel van Diepen
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Marie Evans
- Renal Unit, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University hospital, Stockholm, Sweden
| | - Claudia Torino
- Institute of Clinical Physiology – National Research Council, Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy
| | - Antonio Vilasi
- Institute of Clinical Physiology – National Research Council, Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy
| | - Maciej Szymczak
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | | | - Christoph Wanner
- Division of Nephrology, University Hospital of Würzburg, Würzburg, Germany
| | - Barnaby Hole
- Population health sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Samantha Hayward
- Population health sciences, Bristol Medical School, University of Bristol, Bristol, UK
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23
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Stepanova N. Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes. Biomedicines 2024; 12:2377. [PMID: 39457689 PMCID: PMC11505255 DOI: 10.3390/biomedicines12102377] [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: 09/21/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.
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Affiliation(s)
- Natalia Stepanova
- State Institution “O.O. Shalimov National Scientific Center of Surgery and Transplantology, National Academy of Medical Science of Ukraine”, 03126 Kyiv, Ukraine;
- Medical Center “Nephrocenter”, 03057 Kyiv, Ukraine
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24
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Zhao Z, Wan Y, Fu H, Ying S, Zhang P, Meng H, Song Y, Fu N. Lipid-lowering drugs and risk of rapid renal function decline: a mendelian randomization study. BMC Med Genomics 2024; 17:248. [PMID: 39379957 PMCID: PMC11463126 DOI: 10.1186/s12920-024-02020-4] [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: 10/17/2023] [Accepted: 09/25/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) patients face the risk of rapid kidney function decline leading to adverse outcomes like dialysis and mortality. Lipid metabolism might contribute to acute kidney function decline in CKD patients. Here, we utilized the Mendelian Randomization approach to investigate potential causal relationships between drug target-mediated lipid phenotypes and rapid renal function decline. METHODS In this study, we utilized two methodologies: summarized data-based Mendelian randomization (SMR) and inverse variance-weighted Mendelian randomization (IVW-MR), to approximate exposure to lipid-lowering drugs. This entailed leveraging expression quantitative trait loci (eQTL) for drug target genes and genetic variants proximal to drug target gene regions, which encode proteins associated with low-density lipoprotein (LDL) cholesterol, as identified in genome-wide association studies. The objective was to investigate causal associations with the progression of rapid kidney function decline. RESULTS The SMR analysis revealed a potential association between high expression of PCSK9 and rapid kidney function decline (OR = 1.11, 95% CI= [1.001-1.23]; p = 0.044). Similarly, IVW-MR analysis demonstrated a negative association between LDL cholesterol mediated by HMGCR and kidney function decline (OR = 0.74, 95% CI = 0.60-0.90; p = 0.003). CONCLUSION Genetically predicted inhibition of HMGCR is linked with the progression of kidney function decline, while genetically predicted PCSK9 inhibition is negatively associated with kidney function decline. Future research should incorporate clinical trials to validate the relevance of PCSK9 in preventing kidney function decline.
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Affiliation(s)
- Zhicheng Zhao
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Yu Wan
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Han Fu
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shuo Ying
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Peng Zhang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Haoyu Meng
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Yu Song
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Naikuan Fu
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China.
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25
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Hyun YY, Kim KS, Hong S, Han K, Park CY. Fenofibrate and risk of end-stage renal disease: A nationwide cohort study. Diabetes Obes Metab 2024; 26:4583-4590. [PMID: 39075919 DOI: 10.1111/dom.15815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 06/30/2024] [Accepted: 07/03/2024] [Indexed: 07/31/2024]
Abstract
AIM Previous studies have shown that fenofibrate improves outcomes such as albuminuria and estimated glomerular filtration rate decline. We hypothesize that fenofibrate has renoprotective effects and prevents or delays the development of end-stage renal disease. The objective of this study is to investigate the risk of incident end-stage renal disease in relation to fenofibrate treatment in patients who are already taking statins. MATERIALS AND METHODS We performed a nationwide population-based cohort study using data from the Korea National Health Information Database from 2010 to 2017. Among adults using statins, 413 715 fenofibrate users were compared with 413 715 fenofibrate non-users after 1:1 age, sex and triglyceride matching. The endpoint of this study was incident end-stage renal disease. RESULTS During a median 3.96-year follow-up, the incidence per 1000 person years of end-stage renal disease was lower in fenofibrate users than in fenofibrate non-users (0.885 vs. 0.960, p < 0.0001). The hazard ratio for end-stage renal disease was lower (0.763, 95% confidence interval 0.710-0.821) in fenofibrate users. This association was significant in patients with hypertension, proteinuria and an estimated glomerular filtration rate <60 mL/min/1.732. CONCLUSIONS Fenofibrate use in patients taking statins with either hypertension, proteinuria, or decreased estimated glomerular filtration rate is associated with a low risk of incident end-stage renal disease. To confirm the renoprotective effect of fenofibrate in chronic kidney disease, a randomized controlled trial is warranted.
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Affiliation(s)
- Young Youl Hyun
- Division of Nephorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sangmo Hong
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Cheol-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Młynarska E, Buławska D, Czarnik W, Hajdys J, Majchrowicz G, Prusinowski F, Stabrawa M, Rysz J, Franczyk B. Novel Insights into Diabetic Kidney Disease. Int J Mol Sci 2024; 25:10222. [PMID: 39337706 PMCID: PMC11432709 DOI: 10.3390/ijms251810222] [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: 08/20/2024] [Revised: 09/20/2024] [Accepted: 09/21/2024] [Indexed: 09/30/2024] Open
Abstract
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.
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Affiliation(s)
- Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Dominika Buławska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Witold Czarnik
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Filip Prusinowski
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Magdalena Stabrawa
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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27
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Bellos I, Lagiou P, Benetou V, Marinaki S. Efficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis. Lipids Health Dis 2024; 23:293. [PMID: 39261803 PMCID: PMC11389595 DOI: 10.1186/s12944-024-02276-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 08/28/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND Dyslipidemia represents an important risk factor for cardiovascular diseases, although its optimal management after kidney transplantation remains unclear. The present meta-analysis aimed to shed light on the efficacy and safety of statins among kidney transplant recipients, evaluating their potential effects on the risk of cardiovascular events, mortality and graft survival. METHODS Medline, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from their inception through April 20, 2024. Both randomized controlled trials and observational studies evaluating the effects of statin administration after kidney transplantation were held eligible. Random-effects models were fitted using the maximum likelihood method, while the certainty of evidence was appraised following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. RESULTS Overall, 27 studies (10 randomized controlled trials and 17 observational studies) were included. Statin use compared to no use was associated with a lower risk of major adverse cardiovascular events [Relative risk (RR): 0.87, 95% confidence interval (CI): 0.67-0.96, moderate certainty] and overall mortality (RR: 0.84, 95% CI: 0.74-0.94, low certainty). The risk of graft loss did not differ between the compared groups (RR: 0.72, 95% CI: 0.48-1.08, very low certainty). Regarding safety endpoints, statin use was associated with a lower risk of hepatotoxicity (RR: 0.81, 95% CI: 0.70-0.93, moderate certainty), but with a greater risk of rhabdomyolysis (RR: 1.37, 95% CI: 1.10-1.70, low certainty) and cataract (RR: 1.22, 95% CI: 1.14-1.31, moderate certainty). No statistically significant differences between the compared groups with and without statin use were observed concerning the risk of creatine kinase elevation, post-transplant diabetes mellitus, hip fracture, venous thromboembolism, or cancer. CONCLUSIONS Among kidney transplant recipients, statin use is associated with a lower risk of cardiovascular events and better patient survival, presenting an acceptable safety profile. Further large-scale studies are needed to determine the optimal statin dosing strategy and lipid-lowering goals, depending on comorbidities and immunosuppression regimens. REGISTRATION https://doi.org/10.17504/protocols.io.5qpvok3yzl4o/v1 .
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Affiliation(s)
- Ioannis Bellos
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias str, Athens, 115 27, Greece.
- Department of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias str, Athens, 115 27, Greece.
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias str, Athens, 115 27, Greece
| | - Vassiliki Benetou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias str, Athens, 115 27, Greece
| | - Smaragdi Marinaki
- Department of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias str, Athens, 115 27, Greece
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Torino C, Carbone F, Pizzini P, Mezzatesta S, D'Arrigo G, Gori M, Liberale L, Moriero M, Michelauz C, Frè F, Isoppo S, Gavoci A, La Rosa F, Scuricini A, Tirandi A, Ramoni D, Mallamaci F, Tripepi G, Montecucco F, Zoccali C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients. Eur J Clin Invest 2024; 54:e14235. [PMID: 38733147 DOI: 10.1111/eci.14235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 04/05/2024] [Accepted: 04/11/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. METHODS The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. RESULTS During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HRfor1ln unit increase: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HRfor1ln unit increase: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HRfor 1 ln unit increase: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HRfor1ln unit increase: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HRfor1ln unit increase: 1.88, 95% CI 1.27-2.78, p =.002; Men, HRfor1ln unit increase: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02). CONCLUSIONS PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.
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Affiliation(s)
- Claudia Torino
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Patrizia Pizzini
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
| | - Sabrina Mezzatesta
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
| | - Graziella D'Arrigo
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
| | | | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Margherita Moriero
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Cristina Michelauz
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Federica Frè
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Simone Isoppo
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Aurora Gavoci
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Federica La Rosa
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Alessandro Scuricini
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Amedeo Tirandi
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Davide Ramoni
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Francesca Mallamaci
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
- Nephrology, Hypertension and Renal Transplantation Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Giovanni Tripepi
- Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Carmine Zoccali
- Renal Research Institute, New York, USA
- IPNET, c/o Nefrologia delGrande Ospedale Metropolitano, Reggio Calabria, Italy
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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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Li SS, Liu QJ, Bao JX, Lu MT, Deng BQ, Li WW, Cao CC. Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway. Transl Res 2024; 271:26-39. [PMID: 38734063 DOI: 10.1016/j.trsl.2024.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 04/28/2024] [Accepted: 05/08/2024] [Indexed: 05/13/2024]
Abstract
Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to β-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.
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Affiliation(s)
- Shan-Shan Li
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Qiao-Juan Liu
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Jia-Xin Bao
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Meng-Ting Lu
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Bing-Quan Deng
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Wen-Wen Li
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China
| | - Chang-Chun Cao
- Department of Nephrology, Sir Run Run hospital, Nanjing Medical University, Nanjing, China.
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Mencarelli F, Azukaitis K, Kirchner M, Bayazit A, Duzova A, Canpolat N, Bulut IK, Obrycki L, Ranchin B, Shroff R, Caliskan S, Candan C, Yilmaz A, Özcakar ZB, Halpay H, Kiyak A, Erdogan H, Gellermann J, Balat A, Melk A, Schaefer F, Querfeld U. Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study. Pediatr Nephrol 2024; 39:2759-2772. [PMID: 38720111 PMCID: PMC11272819 DOI: 10.1007/s00467-024-06389-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 04/11/2024] [Accepted: 04/11/2024] [Indexed: 07/26/2024]
Abstract
BACKGROUND Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.
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Affiliation(s)
- Francesca Mencarelli
- Pediatric Nephrology Unit, Department of Pediatrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Karolis Azukaitis
- Clinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Marietta Kirchner
- Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Aysun Bayazit
- Department of Pediatric Nephrology, Cukurova University, Adana, Turkey
| | - Ali Duzova
- Division of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Nur Canpolat
- Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ipek Kaplan Bulut
- Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Lukasz Obrycki
- Department of Nephrology and Arterial Hypertension, Children's Memorial Health Institute, Warsaw, Poland
| | - Bruno Ranchin
- Pediatric Nephrology Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Université de Lyon, Lyon, France
| | - Rukshana Shroff
- UCL Great Ormond Street Institute of Child Health, London, UK
| | - Salim Caliskan
- Division of Pediatric Nephrology, Göztepe Hospital, Istanbul Medeniyet University, Istanbul, Turkey
| | - Cengiz Candan
- Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Alev Yilmaz
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Zeynep Birsin Özcakar
- Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey
| | - Harika Halpay
- Department of Pediatric Nephrology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Aysel Kiyak
- Division of Pediatric Nephrology, Department of Pediatrics, Bakirkoy Children's Hospital, Istanbul, Turkey
| | - Hakan Erdogan
- Division of Pediatric Nephrology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Jutta Gellermann
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité University Hospital, Berlin, Germany
| | - Ayse Balat
- Department of Pediatric Nephrology, Gaziantep University, Gaziantep, Turkey
| | - Anette Melk
- Department of Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Franz Schaefer
- Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany
| | - Uwe Querfeld
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité University Hospital, Berlin, Germany.
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32
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Kanbay M, Guldan M, Ozbek L, Copur S, Covic AS, Covic A. Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum. Eur J Intern Med 2024; 127:1-14. [PMID: 39030148 DOI: 10.1016/j.ejim.2024.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/25/2024] [Accepted: 07/11/2024] [Indexed: 07/21/2024]
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives.
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Affiliation(s)
- Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.
| | - Mustafa Guldan
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Lasin Ozbek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Division of Internal Medicine, Koç University School of Medicine, Istanbul, Turkey
| | | | - Adrian Covic
- University of Medicine "Grigore T Popa" Iasi, Romania
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Alasfar S, Me HM, Budhiraja P. Approach to Late Noninfectious Post-Transplant Complications. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:436-449. [PMID: 39232614 DOI: 10.1053/j.akdh.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/16/2024] [Accepted: 05/24/2024] [Indexed: 09/06/2024]
Abstract
The management of noninfectious complications in kidney transplant recipients includes a broad spectrum of conditions, including metabolic issues, cardiovascular diseases, and malignancies, each presenting unique challenges for nephrologists managing these patients. Unlike infectious complications, these noninfectious issues require nuanced, multidisciplinary approaches for prevention, diagnosis, and management, emphasizing the need for personalized care plans. Cardiovascular disease is particularly significant, standing as the primary cause of death post-transplantation, with recent data indicating an overtaking of cancer death rates over infections among kidney transplant recipients. The intricacies of managing these patients, influenced by the burden of kidney disease and immunosuppression, highlight the importance of a collaborative care model. Although nephrologists may not directly treat all these conditions, their understanding of the unique aspects of transplant recipients is crucial. They play a pivotal role in coordinating care with specialists such as cardiologists, endocrinologists, hematologists, and oncologists, ensuring comprehensive management that addresses these specific post-transplant complications. This review discusses the epidemiology, underlying mechanisms, clinical manifestations, and management strategies of various noninfectious complications post-kidney transplant, with a focus on cardiovascular, metabolic, oncologic, and hematologic complications.
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Affiliation(s)
- Sami Alasfar
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ.
| | - Hay Me Me
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ
| | - Pooja Budhiraja
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ
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Acharya PC, Alba R, Krisanapan P, Acharya CM, Suppadungsuk S, Csongradi E, Mao MA, Craici IM, Miao J, Thongprayoon C, Cheungpasitporn W. AI-Driven Patient Education in Chronic Kidney Disease: Evaluating Chatbot Responses against Clinical Guidelines. Diseases 2024; 12:185. [PMID: 39195184 DOI: 10.3390/diseases12080185] [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: 06/18/2024] [Revised: 08/10/2024] [Accepted: 08/13/2024] [Indexed: 08/29/2024] Open
Abstract
Chronic kidney disease (CKD) patients can benefit from personalized education on lifestyle and nutrition management strategies to enhance healthcare outcomes. The potential use of chatbots, introduced in 2022, as a tool for educating CKD patients has been explored. A set of 15 questions on lifestyle modification and nutrition, derived from a thorough review of three specific KDIGO guidelines, were developed and posed in various formats, including original, paraphrased with different adverbs, incomplete sentences, and misspellings. Four versions of AI were used to answer these questions: ChatGPT 3.5 (March and September 2023 versions), ChatGPT 4, and Bard AI. Additionally, 20 questions on lifestyle modification and nutrition were derived from the NKF KDOQI guidelines for nutrition in CKD (2020 Update) and answered by four versions of chatbots. Nephrologists reviewed all answers for accuracy. ChatGPT 3.5 produced largely accurate responses across the different question complexities, with occasional misleading statements from the March version. The September 2023 version frequently cited its last update as September 2021 and did not provide specific references, while the November 2023 version did not provide any misleading information. ChatGPT 4 presented answers similar to 3.5 but with improved reference citations, though not always directly relevant. Bard AI, while largely accurate with pictorial representation at times, occasionally produced misleading statements and had inconsistent reference quality, although an improvement was noted over time. Bing AI from November 2023 had short answers without detailed elaboration and sometimes just answered "YES". Chatbots demonstrate potential as personalized educational tools for CKD that utilize layman's terms, deliver timely and rapid responses in multiple languages, and offer a conversational pattern advantageous for patient engagement. Despite improvements observed from March to November 2023, some answers remained potentially misleading. ChatGPT 4 offers some advantages over 3.5, although the differences are limited. Collaboration between healthcare professionals and AI developers is essential to improve healthcare delivery and ensure the safe incorporation of chatbots into patient care.
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Affiliation(s)
- Prakrati C Acharya
- Division of Nephrology, Texas Tech Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Raul Alba
- Division of Nephrology, Texas Tech Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Pajaree Krisanapan
- Division of Nephrology, Thammasat University Hospital, Pathum Thani 12120, Thailand
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
| | - Chirag M Acharya
- Division of Nephrology, Texas Tech Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand
| | - Eva Csongradi
- Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Michael A Mao
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Iasmina M Craici
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
| | - Jing Miao
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
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Murakami T, Yagishita A, Ayabe K, Sakama S, Hee Lee K, Amino M, Yoshioka K, Ikari Y. Correlation between thromboembolic risk and prevalence of coronary artery disease in patients with atrial fibrillation and impaired renal function. IJC HEART & VASCULATURE 2024; 53:101454. [PMID: 39132304 PMCID: PMC11315156 DOI: 10.1016/j.ijcha.2024.101454] [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: 05/15/2024] [Revised: 06/17/2024] [Accepted: 06/28/2024] [Indexed: 08/13/2024]
Abstract
Background Atrial fibrillation (AF) and coronary artery disease (CAD) often co-occur. The prevalence of coincident AF and CAD, the characteristics of such patients, and the correlation with thromboembolic risk in association with renal function are unclear. Methods and Results We studied 435 consecutive patients who underwent contrast-enhanced computed tomography (CT) before catheter ablation for AF. Nineteen patients with inconclusive CT underwent coronary angiography for a calcified coronary artery. Overall, 87 of the 435 patients had CAD (20.0 %: paroxysmal AF, 63.9 %; persistent AF, 35.2 %; and longstanding AF, 0.9 %). Of these, 17.9 % were newly diagnosed with CAD. There was a stepwise increase in CAD prevalence according to the CHADS2 score (10.1 % at 0, 20.1 % at 1, 24.7 % at 2, 35.1 % at 3, and 41.7 % at ≥ 4 points). Of note, in patients with low estimated glomerular filtration rate < 50 mL/min/1.73 m2, the CAD prevalence increased for all CHADS2 scores (15.4 % at 0, 40.0 % at 1, 32.4 % at 2, 38.5 % at 3, and 50.0 % at ≥ 4 points). Conclusions The prevalence of coexisting CAD increases with the CHADS2 score. This underscores the importance of screening for coexisting CAD in patients who are at high risk for thromboembolic events, particularly in patients with impaired renal function.
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Affiliation(s)
- Tsutomu Murakami
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Atsuhiko Yagishita
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Kengo Ayabe
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Susumu Sakama
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Kyong Hee Lee
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Mari Amino
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Koichiro Yoshioka
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Yuji Ikari
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
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Österman J, Al‐Sodany E, Haugen Löfman I, Barany P, Evans M. Heart failure: the grim reaper of the cardio-renal-metabolic triad. ESC Heart Fail 2024; 11:2334-2343. [PMID: 38659273 PMCID: PMC11287351 DOI: 10.1002/ehf2.14810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 03/19/2024] [Accepted: 04/02/2024] [Indexed: 04/26/2024] Open
Abstract
AIMS Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM. METHODS AND RESULTS We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM. CONCLUSIONS In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.
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Affiliation(s)
- Joakim Österman
- Renal Medicine, Department of Clinical Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Ehab Al‐Sodany
- Renal Medicine, Department of Clinical Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Ida Haugen Löfman
- Department of Medicine Solna, Unit of Cardiology, Heart and Vascular ThemeKarolinska Institutet, Karolinska University HospitalStockholmSweden
| | - Peter Barany
- Renal Medicine, Department of Clinical Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Marie Evans
- Renal Medicine, Department of Clinical Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
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Ma L, Sun F, Zhu K, Han Q, Sun Q. The Predictive Value of Atherogenic Index of Plasma, Non- High Density Lipoprotein Cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and Lipoprotein Combine Index for Stroke Incidence and Prognosis in Maintenance Hemodialysis Patients. Clin Interv Aging 2024; 19:1235-1245. [PMID: 38978964 PMCID: PMC11230120 DOI: 10.2147/cia.s461150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 06/15/2024] [Indexed: 07/10/2024] Open
Abstract
Purpose The serum lipid level is strongly associated with atherosclerosis. However, research on the relationship between lipid-derived indices and acute ischemic stroke (AIS) occurrence in hemodialysis populations is limited. This study aimed to explore the predictive value of lipid-derived indices, including atherogenic index of plasma (AIP), Non- high density lipoprotein cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and lipoprotein combine index (LCI) in clinical practice for the occurrence and prognosis of AIS in hemodialysis patients. Methods A total of 451 patients undergoing maintenance hemodialysis were screened and 350 were enrolled in this study. The lipid parameters exhibit a progressive increase across the tertiles, with values rising from Q1 through Q3. Enrolled patients were divided into three groups (Q1, Q2, and Q3) based on tertiles of AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI values. Kaplan-Meier curves were performed to investigate the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS-free survival in hemodialysis patients. Chi-square analysis was used to explore the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS outcomes in hemodialysis patients. AIS outcomes were assessed using the modified Rankin Scale (mRS). Results Kaplan-Meier analysis revealed that the AIS-free survival rates were significantly higher in the Q1 group compared to Q2 and Q3 groups for AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI. Log rank tests showed statistically significant differences between the Q1 group and the Q2 and Q3 groups (p < 0.05 for all). The proportion of patients with a good outcome mRS was higher in the Q1 group compared to the Q2-Q3 groups (AIP: 0.818 vs 0.792; Non- HDL-C: 0.866 vs 0.767; Non- HDL-C/HDL-C: 0.867 vs 0.767; LCI: 0.938 vs 0.750). Conclusion The four lipid-derived parameters are effective predictors of AIS in patients undergoing hemodialysis, and AIP has a strongest correlation with the risk of AIS. Hemodialysis patients with elevated levels of the four lipid-derived indices had a higher incidence of AIS and poorer functional outcomes compared to those with lower levels. Our conclusions may require confirmation by further research in the future.
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Affiliation(s)
- Lijie Ma
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Fang Sun
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Kaiyi Zhu
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Qiuxia Han
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Qianmei Sun
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
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Ma BM, Elefant N, Tedesco M, Bogyo K, Vena N, Murthy SK, Bheda SA, Yang S, Tomar N, Zhang JY, Husain SA, Mohan S, Kiryluk K, Rasouly HM, Gharavi AG. Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients. Kidney Int 2024; 106:115-125. [PMID: 38521406 PMCID: PMC11410071 DOI: 10.1016/j.kint.2024.02.021] [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: 10/24/2023] [Revised: 01/18/2024] [Accepted: 02/13/2024] [Indexed: 03/25/2024]
Abstract
Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.
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Affiliation(s)
- Becky M Ma
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Division of Nephrology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
| | - Naama Elefant
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Martina Tedesco
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Kelsie Bogyo
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Natalie Vena
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Sarath K Murthy
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Shiraz A Bheda
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Sandy Yang
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Nikita Tomar
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Jun Y Zhang
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Syed Ali Husain
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA
| | - Sumit Mohan
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA
| | - Krzysztof Kiryluk
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Hila Milo Rasouly
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Ali G Gharavi
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
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Kim M, Kim SE, Lee SM, An WS. Effect of pitavastatin on erythrocyte membrane fatty acid content in patients with chronic kidney disease: two-arm parallel randomized controlled trial. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2024; 41:188-195. [PMID: 38715530 PMCID: PMC11294791 DOI: 10.12701/jyms.2024.00094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/26/2024] [Accepted: 04/02/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment. METHODS A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively. RESULTS In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment. CONCLUSION Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.
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Affiliation(s)
- Minna Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Seong Eun Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Su Mi Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Won Suk An
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
- Medical Science Research Center, Dong-A University, Busan, Korea
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Jyrkilä H, Kaartinen K, Martola L, Halminen O, Haukka J, Linna M, Mustonen P, Putaala J, Teppo K, Kinnunen J, Hartikainen J, Airaksinen KEJ, Lehto M. Comorbidity and Medication Trends in Chronic Kidney Disease and Incident Atrial Fibrillation: A Nationwide Cohort Study. Nephron Clin Pract 2024; 148:755-767. [PMID: 38861935 DOI: 10.1159/000539603] [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: 12/14/2023] [Accepted: 05/25/2024] [Indexed: 06/13/2024] Open
Abstract
INTRODUCTION Chronic kidney disease (CKD) is associated with an increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. METHODS The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168,233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124,936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. RESULTS At AF diagnosis eGFR <60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR <60 mL/min/1.73 m2 prevalence of hypertension, dyslipidaemia, and diabetes increased from 82 to 88%, from 50 to 66% and from 25 to 33%, respectively (<0.001). Throughout the observation period, lipid-lowering medication was underused. CONCLUSION More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the use of survival-affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.
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Affiliation(s)
- Heini Jyrkilä
- Helsinki University Hospital, Abdominal Center, Department of Nephrology and University of Helsinki, Helsinki, Finland
| | - Kati Kaartinen
- Helsinki University Hospital, Abdominal Center, Department of Nephrology and University of Helsinki, Helsinki, Finland
| | - Leena Martola
- Helsinki University Hospital, Abdominal Center, Department of Nephrology and University of Helsinki, Helsinki, Finland
| | - Olli Halminen
- Department of Industrial Engineering and Management, Aalto University, Espoo, Finland
| | - Jari Haukka
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Miika Linna
- University of Eastern Finland, Kuopio, Finland
| | - Pirjo Mustonen
- Department of Internal Medicine, Central Finland Health Care District, Jyväskylä, Finland
| | - Jukka Putaala
- Helsinki University Hospital, Department of Neurology and University of Helsinki, Helsinki, Finland
| | - Konsta Teppo
- Turku University Hospital, Department of Cardiology and University of Turku, Turku, Finland
| | - Janne Kinnunen
- Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Juha Hartikainen
- Kuopio University Hospital, Heart Center, Department of Cardiology and University of Eastern Finland, Kuopio, Finland
| | - K E Juhani Airaksinen
- Turku University Hospital, Department of Cardiology and University of Turku, Turku, Finland
| | - Mika Lehto
- Jorvi Hospital, HUS Helsinki University Hospital, Espoo, Finland
- University of Helsinki, Helsinki, Finland
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Edmonston D, Lydon E, Mulder H, Chiswell K, Lampron Z, Marsolo K, Goss A, Ayoub I, Shah RC, Chang AR, Ford DE, Jones WS, Fonesca V, Machineni S, Fort D, Butler J, Hunt KJ, Pitlosh M, Rao A, Ahmad FS, Gordon HS, Hung AM, Hwang W, Bosworth HB, Pagidipati NJ. Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes. JAMA Netw Open 2024; 7:e2418808. [PMID: 38922613 PMCID: PMC11208975 DOI: 10.1001/jamanetworkopen.2024.18808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 04/25/2024] [Indexed: 06/27/2024] Open
Abstract
Importance Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care. Objective To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D. Design, Setting, and Participants This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023. Exposures Demographics, lifestyle factors, comorbidities, medications, and laboratory results. Main Outcomes and Measures Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit. Results Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment. Conclusions and Relevance In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.
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Affiliation(s)
- Daniel Edmonston
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Elizabeth Lydon
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Hillary Mulder
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Karen Chiswell
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Zachary Lampron
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Keith Marsolo
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina
| | - Ashley Goss
- Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut
| | - Isabelle Ayoub
- Division of Nephrology; Department of Medicine, The Ohio State University Wexner Medical Center, Columbus
| | - Raj C. Shah
- Department of Family and Preventive Medicine, Rush University Medical Center, Chicago, Illinois
- Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois
| | - Alexander R. Chang
- Department of Population Health Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania
| | - Daniel E. Ford
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - W. Schuyler Jones
- Division of Cardiology; Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Vivian Fonesca
- Division of Endocrinology; Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Sriram Machineni
- Division of Endocrinology, University of North Carolina, Chapel Hill
| | | | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, Texas
| | - Kelly J. Hunt
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Max Pitlosh
- Department of Family & Preventive Medicine, Rush University Medical Center, Chicago, Illinois
| | - Ajaykumar Rao
- Department of Endocrinology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania
| | - Faraz S. Ahmad
- Division of Cardiology; Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Howard S. Gordon
- Division of Academic Internal Medicine and Geriatrics; Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago
| | - Adriana M. Hung
- Division of Nephrology, Department of Medicine at Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Wenke Hwang
- Division of Health Services and Behavioral Research; Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania
| | - Hayden B. Bosworth
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina
- Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Medical Center, Durham, North Carolina
- Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
- Duke University School of Nursing, Durham, North Carolina
| | - Neha J. Pagidipati
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
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Campillo S, Gutiérrez-Calabrés E, García-Miranda S, Griera M, Fernández Rodríguez L, de Frutos S, Rodríguez-Puyol D, Calleros L. Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease. Cell Commun Signal 2024; 22:264. [PMID: 38734696 PMCID: PMC11088758 DOI: 10.1186/s12964-024-01646-2] [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: 01/20/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. METHODS CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. RESULTS The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. CONCLUSIONS ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.
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Affiliation(s)
- Sofía Campillo
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain.
| | - Elena Gutiérrez-Calabrés
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
| | - Susana García-Miranda
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
| | - Mercedes Griera
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
| | - Loreto Fernández Rodríguez
- Biomedical Research Foundation and Nephrology Unit, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - Sergio de Frutos
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
| | - Diego Rodríguez-Puyol
- Department of Medicine and Medical Specialties, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
- Biomedical Research Foundation and Nephrology Unit, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - Laura Calleros
- Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain
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Yeung KC, Fryml E, Lanktree MB. How Does ADPKD Severity Differ Between Family Members? Kidney Int Rep 2024; 9:1198-1209. [PMID: 38707833 PMCID: PMC11068977 DOI: 10.1016/j.ekir.2024.01.053] [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: 09/26/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 05/07/2024] Open
Abstract
Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability in phenotype and risk of subsequent kidney failure. Despite an established genotype-phenotype correlation in cystic kidney diseases, incomplete penetrance and variable disease expressivity are present as is the case in all monogenic diseases. In family members with autosomal dominant polycystic kidney disease (ADPKD), the same causal variant is responsible in all affected family members; however, there can still be striking discordance in phenotype severity. This narrative review explores contributors to within-family discordance in ADPKD severity. Cases of biallelic and digenic inheritance, where 2 rare pathogenic variants in cystogenic genes are coexistent in one family, account for a small proportion of within-family discordance. Genetic background, including cis and trans factors and the polygenic propensity for comorbid disease, also plays a role but has not yet been exhaustively quantified. Environmental exposures, including diet; smoking; alcohol, salt, and protein intake, and comorbid diseases, including obesity, diabetes, hypertension, kidney stones, dyslipidemia, and additional coexistent kidney diseases all contribute to ADPKD phenotypic variability among family members. Given that many of the factors contributing to phenotype variability are preventable, modifiable, or treatable, health care providers and patients need to be aware of these factors and address them in the treatment of ADPKD.
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Affiliation(s)
- Klement C. Yeung
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Elise Fryml
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Matthew B. Lanktree
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of Nephrology, St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
- Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, Hamilton, Ontario, Canada
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Al-Ashwal FY, Syed Sulaiman SA, Sheikh Ghadzi SM, Harun SN, Halboup A, Kubas MA. The Impact of an Educational Intervention on Enhancing Clinical Knowledge of Physicians and Pharmacists Regarding Statins and Monitoring Parameters: The Experience of a Tertiary Teaching Hospital. ADVANCES IN MEDICAL EDUCATION AND PRACTICE 2024; 15:357-368. [PMID: 38707544 PMCID: PMC11069367 DOI: 10.2147/amep.s445610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 04/19/2024] [Indexed: 05/07/2024]
Abstract
Introduction Understanding the latest guideline recommendations is crucial for healthcare professionals to apply statin therapy effectively. Thus, the purpose of this study was to evaluate the efficacy of an educational intervention in enhancing the awareness and understanding of physicians and pharmacists concerning risk assessment of Atherosclerotic cardiovascular disease (ASCVD) and the role of statin therapy. Methods This pre- and post-intervention study was conducted in Sana'a, Yemen's capital city, at the University of Science and Technology Hospital. The study was done between 11/2021-12/2021, and two separate educational sessions were held. The McNemar's test and Wilcoxon signed-rank test were employed as necessary. Results Participants' awareness of the Framingham CVD risk calculator improved significantly from 40.4% pre-intervention to 78.7% post-intervention. Similarly, understanding of the parameters used in the 10-year ASCVD Risk calculator rose from 46.8% pre-intervention to 76.6% post-intervention. The ability to identify high, moderate, and low-intensity statin therapy, for instance, increased from 34% to 63.8% post-intervention. Regarding statins' contraindications, safety, and efficacy monitoring parameters, pre-intervention knowledge was unsatisfactory, and the educational intervention improved it significantly (p <0.05). For physicians, the median ASCVD risk assessment knowledge score was significantly improved from 4 (IQR = 3-5) pre-intervention to 7 (6.25-8) immediately post-intervention, while the statin therapy clinical knowledge median score significantly improved from 3 (1.25-6.5) to 9 (7.25-14.75) post-education intervention, p-values were 0.002 and 0.003; respectively. For pharmacists, a similar significant improvement (p <0.05) in the overall knowledge scores for both ASCVD risk assessment and statin therapy was noted. Conclusion The educational intervention improved participants' knowledge of statin therapy and ASCVD risk assessment. Therefore, further education lectures and training programs through continuing medical education on the up-to-date guidelines' recommendations should be regularly implemented to raise awareness and improve the clinical knowledge and appropriateness of statins use in clinical settings..
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Affiliation(s)
- Fahmi Y Al-Ashwal
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Science and Technology, Sana’a, Yemen
- Department of Clinical Pharmacy, College of Pharmacy, Al-Ayen Iraqi University, Thi-Qar, Iraq
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
| | - Syed Azhar Syed Sulaiman
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
| | | | - Sabariah Noor Harun
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
| | - Abdulsalam Halboup
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Science and Technology, Sana’a, Yemen
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
| | - Mohammed Abdullah Kubas
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Science and Technology, Sana’a, Yemen
- Clinical School of Pharmacy & Medical Sciences, Lebanese International University (LIU), Sana’a, Yemen
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Sundström J, Norhammar A, Karayiannides S, Bodegård J, Gustafsson S, Cars T, Eriksson Svensson M, Ärnlöv J. Are there lost opportunities in chronic kidney disease? A region-wide cohort study. BMJ Open 2024; 14:e074064. [PMID: 38643002 PMCID: PMC11033666 DOI: 10.1136/bmjopen-2023-074064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 04/03/2024] [Indexed: 04/22/2024] Open
Abstract
OBJECTIVES Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention. DESIGN AND SETTING Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020. PARTICIPANTS All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records. OUTCOME MEASURES We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population. RESULTS We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD. CONCLUSIONS While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.
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Affiliation(s)
- Johan Sundström
- Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Anna Norhammar
- Cardiology Unit, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden
- Capio S:t Görans Hospital, Stockholm, Sweden
| | - Stelios Karayiannides
- Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden
- Center for Diabetes, Academic Specialist Center, Region Stockholm, Stockholm, Sweden
| | - Johan Bodegård
- Cardiovascular, Renal and Metabolism, Medical Department, BioPharmaceuticals, AstraZeneca PLC, Oslo, Norway
| | | | | | - Maria Eriksson Svensson
- Department of Medical Sciences, Renal Medicine, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala, Sweden
| | - Johan Ärnlöv
- Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- School of Health and Social Studies, Dalarna University, Falun, Dalarna, Sweden
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Weon B, Jang Y, Jo J, Jin W, Ha S, Ko A, Oh YK, Lim CS, Lee JP, Won S, Lee J. Association between dyslipidemia and the risk of incident chronic kidney disease affected by genetic susceptibility: Polygenic risk score analysis. PLoS One 2024; 19:e0299605. [PMID: 38626061 PMCID: PMC11020804 DOI: 10.1371/journal.pone.0299605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/13/2024] [Indexed: 04/18/2024] Open
Abstract
BACKGROUND The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). METHODS We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. RESULTS In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. CONCLUSIONS This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.
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Affiliation(s)
- Boram Weon
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | | | - Jinyeon Jo
- Department of Public Health Sciences, Institute of Health & Environment, School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Wencheng Jin
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seounguk Ha
- Korea Medical Institute, Seoul, Republic of Korea
| | - Ara Ko
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yun Kyu Oh
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sungho Won
- Rexsoft Corporation, Seoul, Republic of Korea
- Department of Public Health Sciences, Institute of Health & Environment, School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Jeonghwan Lee
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
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Kratky V, Valerianova A, Hruskova Z, Tesar V, Malik J. Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy. Curr Atheroscler Rep 2024; 26:103-109. [PMID: 38289577 DOI: 10.1007/s11883-024-01191-w] [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] [Accepted: 01/18/2024] [Indexed: 04/04/2024]
Abstract
PURPOSE OF REVIEW Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. RECENT FINDINGS Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.
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Affiliation(s)
- Vojtech Kratky
- Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Anna Valerianova
- 3rd Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 499/2, 128 08, Prague, Czech Republic
| | - Zdenka Hruskova
- Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
| | - Vladimir Tesar
- Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Jan Malik
- 3rd Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 499/2, 128 08, Prague, Czech Republic
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d'Hervé Q, Girerd N, Bozec E, Lamiral Z, Panisset V, Frimat L, Huttin O, Girerd S. Factors associated with changes in echocardiographic parameters following kidney transplantation. Clin Res Cardiol 2024; 113:412-424. [PMID: 37084138 DOI: 10.1007/s00392-023-02203-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 04/11/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes. METHODS One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared. RESULTS A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m2 post-KT vs. 30.9 mL/m2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT. DISCUSSION/CONCLUSION Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling.
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Affiliation(s)
- Q d'Hervé
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - N Girerd
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116, University Hospital of Nancy, F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - E Bozec
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116, University Hospital of Nancy, F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - Z Lamiral
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116, University Hospital of Nancy, F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - V Panisset
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - L Frimat
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - O Huttin
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116, University Hospital of Nancy, F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
- Cardiology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - S Girerd
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116, University Hospital of Nancy, F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France.
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Yoon J, Han T, Heo SJ, Kwon YJ. Comprehensive assessment of the combined impact of dyslipidemia and inflammation on chronic kidney disease development: A prospective cohort study. J Clin Lipidol 2024; 18:e251-e260. [PMID: 38233308 DOI: 10.1016/j.jacl.2024.01.002] [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: 09/07/2023] [Revised: 12/28/2023] [Accepted: 01/01/2024] [Indexed: 01/19/2024]
Abstract
BACKGROUND There remains a limited comprehensive understanding of how dyslipidemia and chronic inflammation collectively contribute to the development of chronic kidney disease (CKD). OBJECTIVE We aimed to identify clusters of individuals with five variables, including lipid profiles and C-reactive protein (CRP) levels, and to assess whether the clusters were associated with incident CKD risk. METHODS We used the Korean Genome and Epidemiology Study-Ansan and Ansung data. K-means clustering analysis was performed to identify distinct clusters based on total cholesterol, triglyceride, non-high-density lipoprotein (HDL)-C, HDL-C, and CRP levels. Cox proportional hazards models were used to examine the association between incident CKD risk and the different clusters. RESULTS During the mean 10-year follow-up period, CKD developed in 1,645 participants (690 men and 955 women) among a total of 8,053 participants with a mean age of 51.8 years. Four distinct clusters were identified: C1, low cholesterol group (LC); C2, high-density lipoprotein cholesterol group (HC); C3, insulin resistance and inflammation group (IIC); and C4, dyslipidemia and inflammation group (DIC). Cluster 4 had a significantly higher risk of incident CKD compared to clusters 2 (hazard ratio (HR) 1.455 [95% confidence interval (CI) 1.234-1.715]; p < 0.001) and cluster 1 (HR 1.264 [95% CI 1.067-1.498]; p = 0.007) after adjusting for confounders. Cluster 3 had a significantly higher risk of incident CKD compared to clusters 2 and 1. CONCLUSION Clusters 4 and 3 had higher risk of incident CKD compared to clusters 2 and 1. The combination of dyslipidemia with inflammation or insulin resistance with inflammation appears to be pivotal in the development of incident CKD.
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Affiliation(s)
- Jihyun Yoon
- Department of Family Medicine, Korean University Anam Hospital, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02481, Republic of Korea (Dr Yoon)
| | - Taehwa Han
- Health-IT Center, Yonsei University Severance Hospital, Seoul, 03722, Republic of Korea (Dr Han)
| | - Seok-Jae Heo
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea (Dr Heo).
| | - Yu-Jin Kwon
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University of College of Medicine, Seoul, 03722, Republic of Korea (Dr Kwon).
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