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Nishimoto M, Hasegawa T, Murashima M, Noma H, Nishiwaki H, Yamada S, Mizukami A, Saito H, Kimura H, Taniguchi M, Hamano T, Fukagawa M. Efficacy and Safety of Phosphate-Lowering Agents for Adult Patients with CKD Requiring Dialysis: A Network Meta-Analysis. Clin J Am Soc Nephrol 2025; 20:676-696. [PMID: 40085178 PMCID: PMC12097192 DOI: 10.2215/cjn.0000000665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 03/06/2025] [Indexed: 03/16/2025]
Abstract
Key Points Sevelamer was associated with lower all-cause mortality compared with calcium-based agents. Sucroferric oxyhydroxide and tenapanor were estimated to rank high in lowering all-cause mortality compared with other phosphate-lowering agents. Sucroferric oxyhydroxide and lanthanum were associated with slower progression of coronary artery calcium score compared with calcium-based agents. Background It is necessary to update the evidence of each phosphate-lowering agent on dialysis patients. Methods From the CENTRAL, MEDLINE, Embase, and ClinicalTrial.gov databases, randomized controlled trials using oral phosphate-lowering agents on adult patients requiring maintenance dialysis were extracted. The treatment period was required for 8 or more weeks, and the risk of bias was assessed according to the Cochrane Collaboration method. The outcomes were all-cause mortality, cardiovascular mortality, gastrointestinal events, fracture, coronary artery calcium score (CACS), serum calcium, phosphate, intact parathyroid hormone, and bicarbonate levels. A network meta-analyses using multivariate random-effects models were performed for assessing the comparative effectiveness. The ranking of the phosphate-lowering agents was assessed using a surface under the cumulative ranking curve. Results A total of 70 randomized controlled trials involving 15,551 participants were included. Eleven phosphate-lowering agents including calcium-based agents, sevelamer, bixalomer, lanthanum, sucroferric oxyhydroxide, ferric citrate, tenapanor, magnesium, nicotinamide, aluminum, and sucralfate were assessed. Sevelamer was significantly associated with lower all-cause mortality compared with calcium-based agents (risk ratio [95% confidence interval]: 0.59 [0.37 to 0.94]), and sucroferric oxyhydroxide and tenapanor were estimated to rank high in lowering all-cause mortality on the basis of the surface under the cumulative ranking curve. The risk of gastrointestinal events was the highest with nicotinamide, followed by sucroferric oxyhydroxide. Compared with calcium-based agents, CACS was significantly lower among those on lanthanum and sucroferric oxyhydroxide (standardized mean difference [95% confidence interval]: −0.26 [−0.52 to −0.01] and −0.50 [−0.95 to−0.06], respectively). Serum calcium levels were higher, and serum intact parathyroid hormone levels were lower in patients treated with calcium-based agents. Except for sevelamer, serum bicarbonate levels for all other agents were higher compared with placebo. Conclusions Compared with calcium-based agents, sevelamer was associated with lower all-cause mortality, and sucroferric oxyhydroxide and lanthanum were associated with slower progression of CACS. Potential benefits and harms should be considered when selecting phosphate-lowering agents (International prospective register of systematic reviews: CRD42022328388).
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Affiliation(s)
| | - Takeshi Hasegawa
- Institute of Clinical Epidemiology (iCE), Showa Medical University, Tokyo, Japan
- Department of Hygiene, Public Health and Preventive Medicine, Showa University Graduate School of Medicine, Tokyo, Japan
- Department of Nephrology, Showa University Graduate School of Medicine, Tokyo, Japan
- Showa University Research Administration Center, Showa Medical University, Japan
| | - Miho Murashima
- Division of Nephrology, Department of Internal Medicine, Kindai University Faculty of Medicine, Osaka, Japan
| | - Hisashi Noma
- Department of Interdisciplinary Statistical Mathematics, The Institute of Statistical Mathematics, Tokyo, Japan
| | - Hiroki Nishiwaki
- Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Shunsuke Yamada
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Aya Mizukami
- Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Hirotaka Saito
- Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima, Japan
| | - Hiroshi Kimura
- Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima, Japan
| | | | - Takayuki Hamano
- Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
- Department of Nephrology, The University of Osaka Graduate School of Medicine, Osaka, Japan
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Kanagawa, Japan
- Department of Internal Medicine, Ikegami General Hospital, Tokyo, Japan
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Akiyama T, Iwazu Y, Usui J, Ebihara I, Ishizu T, Kobayashi M, Maeda Y, Kobayashi H, Yamagata K, Kuro-O M. Serum calciprotein particle-to-phosphate ratio as a predictor of cardiovascular events in incident hemodialysis patients. Ther Apher Dial 2025; 29:178-188. [PMID: 39229751 DOI: 10.1111/1744-9987.14203] [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: 02/23/2024] [Revised: 07/18/2024] [Accepted: 08/16/2024] [Indexed: 09/05/2024]
Abstract
INTRODUCTION Recent studies have identified increased blood calciprotein particle (CPP) levels as risk factors for vascular calcification and cardiovascular events in patients undergoing maintenance hemodialysis. Although positively correlated with serum phosphate levels, serum CPP levels vary considerably among patients with similar serum phosphate levels. We investigated the capacity of the ratio of serum CPP levels to serum phosphate levels (CPP/Pi ratio) to predict cardiovascular events in incident hemodialysis patients compared to the serum calcification propensity test (T50). METHODS AND RESULTS The association between the CPP/Pi ratio and major adverse cardiac and cerebrovascular events (MACCE) was investigated in 174 incident hemodialysis patients. Multivariate analysis revealed that the CPP/Pi ratio was independently associated with MACCE [hazard ratio 1.60, 95% confidence interval (1.15-2.23), p = 0.006] but serum T50 levels were not. CONCLUSIONS The CPP/Pi ratio is a useful, novel biomarker for predicting the risk of cardiovascular events in patients undergoing incident hemodialysis.
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Affiliation(s)
- Tomoki Akiyama
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yoshitaka Iwazu
- Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Joichi Usui
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Itaru Ebihara
- Department of Nephrology, Mito Saiseikai General Hospital, Mito, Japan
| | - Takashi Ishizu
- Department of Renal and Dialysis Medicine, Tsukuba Central Hospital, Ushiku, Japan
- Central Jin Clinic, Ryugasaki, Japan
| | - Masaki Kobayashi
- Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Yoshitaka Maeda
- Nephrology Division, Department of Internal Medicine, JA Toride Medical Center, Toride, Japan
| | - Hiroaki Kobayashi
- Department of Nephrology, Ibaraki Prefectural Central Hospital, Kasama, Japan
| | - Kunihiro Yamagata
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Makoto Kuro-O
- Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan
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Jinnouchi H, Sakakura K, Fujita H. Deep dive into intravascular coronary imaging in calcified lesions. Cardiovasc Interv Ther 2025; 40:234-244. [PMID: 39899261 DOI: 10.1007/s12928-025-01096-8] [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] [Received: 01/11/2025] [Accepted: 01/14/2025] [Indexed: 02/04/2025]
Abstract
Percutaneous coronary intervention has been developed for patients with coronary artery disease. Calcified lesions are recognized as an unsolved issue where many clinical devices have evolved and some disappeared. Understanding intracoronary imaging of the calcified lesions can help operators to make decisions during the procedure. There are several potential stories of progression of calcification, although a precise mechanism of progression of calcification remains unknown. In the process of a large calcification, it is histologically believed that lipid is replaced by calcification. This process can be observed by intracoronary imaging devices, i.e., intravascular ultrasound and optical coherence tomography. Calcified nodule is a unique type of calcifications. Among the calcified lesions, especially calcified nodule has serious clinical outcomes such as target lesion revascularization (TLR) with stent under-expansion. Additionally, in-stent calcified nodule is a distinctive type of restenosis pattern after stenting to calcified nodule, leading to malignant cycle of repeated TLR. Recently, calcified nodule is divided into two types based on the surface irregularity: (1) eruptive and (2) non-eruptive calcified nodule. Eruptive calcified nodule has higher rate of target vessel revascularization than non-eruptive calcified nodule despite greater stent expansion in eruptive calcified nodule. It is thought that there are differences of component such as the amount of fibrin and the size of calcific nodules between both, although it is common for both to include calcific nodules and fibrin. Histopathological understanding calcified nodule can be helpful to choose the treatment devices during the procedure in the area where there is no correct answer.
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Affiliation(s)
- Hiroyuki Jinnouchi
- Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, Japan.
| | - Kenichi Sakakura
- Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, Japan
| | - Hideo Fujita
- Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, Japan
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Li Y, Ma C, Sheng Y, Huang S, Sun H, Ti Y, Wang Z, Wang F, Chen F, Li C, Guo H, Tang M, Song F, Wang H, Zhong M. TRIB3 mediates vascular calcification by facilitating self-ubiquitination and dissociation of Smurf1 in chronic kidney disease. J Clin Invest 2025; 135:e175972. [PMID: 39932798 PMCID: PMC11957692 DOI: 10.1172/jci175972] [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: 10/03/2023] [Accepted: 02/04/2025] [Indexed: 02/13/2025] Open
Abstract
The osteogenic environment promotes vascular calcium phosphate deposition and aggregation of unfolded and misfolded proteins, resulting in ER stress in chronic kidney disease (CKD). Controlling ER stress through genetic intervention is a promising approach for treating vascular calcification. In this study, we demonstrated a positive correlation between ER stress-induced tribble homolog 3 (TRIB3) expression and progression of vascular calcification in human and rodent CKD. Increased TRIB3 expression promoted vascular smooth muscle cell (VSMC) calcification by interacting with the C2 domain of the E3 ubiquitin-protein ligase Smurf1, facilitating its K48-related self-ubiquitination at Lys381 and Lys383 and subsequent dissociation from the plasma membrane and nuclei. This degeneration of Smurf1 accelerated the stabilization of the osteogenic transcription factors RUNX family transcription factor 2 (Runx2) and SMAD family member 1 (Smad1). C/EBP homologous protein and activating transcription factor 4 are upstream transcription factors of TRIB3 in an osteogenic environment. Genetic KO of TRIB3 or rescue of Smurf1 ameliorated VSMC and vascular calcification by stabilizing Smurf1 and enhancing the degradation of Runx2 and Smad1. Our findings shed light on the vital role of TRIB3 as a scaffold in ER stress and vascular calcification and offer a potential therapeutic option for CKD.
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Affiliation(s)
- Yihui Li
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
- Department of Critical Care Medicine, Qilu Hospital, Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University, Jinan, China
| | - Chang Ma
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Yanan Sheng
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Shanying Huang
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Huaibing Sun
- Department of Organ Transplantation, Qilu Hospital, and
| | - Yun Ti
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Zhihao Wang
- Department of Geriatric Medicine, Qilu Hospital, Shandong University, Jinan, China
| | - Feng Wang
- Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, Shandong, China
| | - Fangfang Chen
- Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China
| | - Chen Li
- Department of Critical Care Medicine, Qilu Hospital, Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University, Jinan, China
| | - Haipeng Guo
- Department of Critical Care Medicine, Qilu Hospital, Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University, Jinan, China
| | - Mengxiong Tang
- Department of Emergency, Qilu Hospital, Shandong University, Jinan, China
| | - Fangqiang Song
- Department of Critical Care Medicine, Affiliated Tengzhou Hospital of Xuzhou Medical University/Tengzhou Central People’s Hospital, Shandong, China
| | - Hao Wang
- Department of Critical Care Medicine, Qilu Hospital, Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University, Jinan, China
| | - Ming Zhong
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
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Hénaut L, Candellier A, Huish S, Issa N, Sinha S, Massy ZA. Valvular calcification in chronic kidney disease: new insights from recent clinical and preclinical studies. Clin Kidney J 2025; 18:i27-i45. [PMID: 40083956 PMCID: PMC11903095 DOI: 10.1093/ckj/sfae421] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Indexed: 03/16/2025] Open
Abstract
Valvular calcification, developing either in the mitral or the aortic valve, is highly prevalent in patients suffering from chronic kidney disease (CKD), in whom their presence correlates with higher cardiovascular and all-cause mortality risk. To date, the exact mechanisms that promote heart valve calcification remain unclear, and none of the treatments tested so far have shown efficacy in preventing valvular fibrocalcific remodelling. It is therefore essential to improve our understanding of the mechanisms involved in the pathological process if we are to find new, effective therapies. The purpose of this review is to (i) summarize our current knowledge of the mechanisms by which CKD and related therapies affect valvular cell activity, (ii) present the latest therapeutic targets identified in preclinical studies, and (iii) discuss the most recent clinical trials evaluating the efficacy of therapies aimed at preventing valvular calcification in CKD.
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Affiliation(s)
- Lucie Hénaut
- MP3CV Laboratory, UR UPJV 7517, CURS, University of Picardie Jules Verne, Amiens, France
| | - Alexandre Candellier
- MP3CV Laboratory, UR UPJV 7517, CURS, University of Picardie Jules Verne, Amiens, France
| | - Sharon Huish
- Department of Nephrology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Donal O'Donoghue Renal Research Centre, Northern Care Alliance NHS Foundation Trust, Salford, UK
| | - Nervana Issa
- MP3CV Laboratory, UR UPJV 7517, CURS, University of Picardie Jules Verne, Amiens, France
| | - Smeeta Sinha
- Donal O'Donoghue Renal Research Centre, Northern Care Alliance NHS Foundation Trust, Salford, UK
- Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
| | - Ziad A Massy
- INSERM Unit 1018, Team 5, CESP, Hôpital Paul Brousse, Paris-Saclay University and Versailles Saint-Quentin-en-Yvelines University (UVSQ), Villejuif, France
- Association pour l'Utilisation du Rein Artificiel dans la région parisienne (AURA), Paris, Paris, France
- Ambroise Paré University Hospital, APHP, Department of Nephrology Boulogne-Billancourt/Paris, Boulogne-Billancourt/Paris, France
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Macias-Cervantes HE, Ocampo-Apolonio MA, Guardado-Mendoza R, Baron-Manzo M, Pereyra-Nobara TA, Hinojosa-Gutiérrez LR, Escalante-Gutiérrez SE, Castillo-Velázquez MA, Aguilar-Guerrero R. Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial. J Nephrol 2025; 38:511-519. [PMID: 39680321 DOI: 10.1007/s40620-024-02154-9] [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: 08/11/2024] [Accepted: 11/05/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Chronic kidney disease (CKD) is associated with several adverse cardiovascular outcomes, including coronary heart disease, heart failure, and arrhythmias. The severity of arterial calcifications predicts the risk of coronary heart disease and increases the risk of premature cardiovascular death. In experimental models, vitamin K1 supplementation appears to reduce coronary artery calcifications. METHODS In this single-center clinical trial (NCT04247087 on 07/09/2019), we randomized 60 Mexican patients on chronic hemodialysis and a coronary calcification score > 10 Agatston units to receive 10 mg intravenous vitamin K1 or placebo at the end of the hemodialysis session thrice weekly for 12 months. The primary outcome was the progression of coronary artery calcifications as assessed by the absolute change in Agatston and coronary calcium volume scores. RESULTS The baseline coronary calcium score was 112.50 (14-2027) Agatston units in the vitamin K1 group and 177 (10-2843); Agatston units in the placebo group (p = 0.71), and after 12 months, the coronary calcium score in the vitamin K1 group was 78.50 (10-1915) Agatston units in the vitamin K1 group versus 344 (10-3323); Agatston units (p = 0.05) in the placebo group. Progression of coronary calcification was 20.8% in the vitamin K1 group versus 44% in the placebo group, with a relative risk (RR) of 0.45 (CI 95% 0.18-1.15). CONCLUSIONS In the Mexican hemodialysis cohort enrolled in this study intravenous vitamin K1 supplementation reduced the progression of coronary artery calcifications by 55% compared with placebo over a 12-month follow-up period.
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Affiliation(s)
- Hilda Elizabeth Macias-Cervantes
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México.
| | - Marco Antonio Ocampo-Apolonio
- Nephrology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | | | - Miguel Baron-Manzo
- Radiology Departament, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Texar Alfonso Pereyra-Nobara
- Director of Health Education and Research, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Luis Ricardo Hinojosa-Gutiérrez
- Radiology Departament, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Sergio Edgardo Escalante-Gutiérrez
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Mario Alberto Castillo-Velázquez
- Cardiology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Rodolfo Aguilar-Guerrero
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
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Kobayashi S, Ohtake T, Mochida Y, Ishioka K, Oka M, Maesato K, Moriya H, Hidaka S. Asymmetric Dimethylarginine (ADMA) as a Novel Risk Factor for Progression of Coronary Artery Calcification in Patients with Chronic Kidney Disease. J Clin Med 2025; 14:1051. [PMID: 40004582 PMCID: PMC11856865 DOI: 10.3390/jcm14041051] [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: 01/08/2025] [Revised: 02/03/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. Methods: We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. Results: The median annual increase in CACS was 23.7 (IQR 2.0-73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values <0.51 and those with ADMA values >0.51 (p < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. Conclusions: ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD.
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Affiliation(s)
| | - Takayasu Ohtake
- Department of Kidney Disease & Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan; (S.K.); (Y.M.); (K.I.); (M.O.); (K.M.); (H.M.); (S.H.)
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Singh PG, Kilari S, Negm AS, Pedersen JM, Montonye DR, McGee KP, Collins JD, Misra S. Development of a Porcine Model of Arteriovenous Fistula Venous Stenosis Treated with Percutaneous Transluminal Angioplasty. J Vasc Interv Radiol 2025; 36:332-339.e10. [PMID: 39461616 PMCID: PMC11995300 DOI: 10.1016/j.jvir.2024.10.020] [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: 02/05/2024] [Revised: 09/27/2024] [Accepted: 10/17/2024] [Indexed: 10/29/2024] Open
Abstract
PURPOSE To develop a porcine model for arteriovenous fistula (AVF) venous stenosis (VS) treated with percutaneous transluminal angioplasty (PTA), and to compare outcomes of plain ordinary balloon angioplasty (POBA) to paclitaxel drug-coated balloon (DCB) angioplasty. MATERIALS AND METHODS Twelve castrated male Yorkshire pigs (4-5 months, 35-45 kg) underwent renal artery embolization to induce chronic kidney disease (CKD). Twenty-eight days later, AVF was created by anastomosing the left external jugular vein to left common carotid artery. The pigs were divided into a pilot group (n = 6) for optimizing the AVF technique (euthanized at Day 4) and a definitive group (n = 6) for validating PTA outcomes (euthanized at Day 42). Stenosis developed at juxta-anastomosis 28 days later and was treated with POBA (pilot group, n = 6; definitive group, n = 3) or DCB (definitive group only, n = 3). The definitive group underwent biweekly 4-dimensional flow magnetic resonance (MR) imaging. RESULTS All animals developed CKD, with significant increases in the levels of blood urea nitrogen (increase of median from 2.6 to 3.2 mmol/L; P < .001) and creatinine (increase of median from 10 to 187 μmol/L, P < .001). In the pilot group, 1 animal had an infected fistula, and AVF patency was 1/5. In the definitive group, the patency was 5/6 because the AVF technique was modified by resecting the sternomastoid muscle and increasing the spatulation. At Day 42 after PTA, the DCB-treated AVF outflow vein showed increasing but statistically insignificant blood flow compared with POBA (DCB, 209.8 mm2 ± 64.4, vs POBA, 170.9 mm2 ± 95.5; P = .934). CONCLUSIONS A porcine model of AVF VS treated with PTA was developed, with blood flow trends favoring DCB over POBA.
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Affiliation(s)
- Prabh G Singh
- Vascular and Interventional Radiology Translational Research Lab, Mayo Clinic, Rochester, Minnesota
| | - Sreenivasulu Kilari
- Vascular and Interventional Radiology Translational Research Lab, Mayo Clinic, Rochester, Minnesota
| | - Ahmed S Negm
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | - Joanne M Pedersen
- Department of Comparative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Dan R Montonye
- Department of Comparative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Kiaran P McGee
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | | | - Sanjay Misra
- Vascular and Interventional Radiology Translational Research Lab, Mayo Clinic, Rochester, Minnesota; Department of Radiology, Mayo Clinic, Rochester, Minnesota.
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9
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Hayashi M, Kato T, Fujimoto K, Watanabe T, Okura H. A case report of left ventricular outflow tract obstruction due to early growth of a calcified amorphous tumour despite normal renal function. Eur Heart J Case Rep 2025; 9:ytae703. [PMID: 39925777 PMCID: PMC11804242 DOI: 10.1093/ehjcr/ytae703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/29/2024] [Accepted: 12/30/2024] [Indexed: 02/11/2025]
Abstract
Background Calcified amorphous tumours (CAT) are non-neoplastic cardiac masses that have been the focus of several recent studies. Moreover, CAT is frequently observed in women and in patients undergoing dialysis. Case summary A woman in her 70 s with normal renal function was referred to our hospital with a chief complaint of shortness of breath upon effort. Echocardiography and contrast-enhanced CT revealed a cardiac mass with calcification in the intervalvular fibrosa (IVF) of the anterior mitral valve, resulting in left ventricular outflow tract (LVOT) obstruction. One year later, the cardiac mass expanded, and the LVOT obstruction worsened. The patient underwent surgical resection of the mass and double-valve replacement with reconstruction of the IVF (commando operation) and myectomy. Histological examination confirmed that the mass was CAT. Discussion We encountered a patient who underwent valve replacement and a commando operation due to rapidly progressive CAT and consequent progression of LVOT obstruction despite normal renal function. In patients with normal renal function, factors other than calcium and phosphate metabolism contribute to the formation of CAT. Understanding the accumulation of CAT is crucial for understanding its pathogenesis.
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Affiliation(s)
- Misayo Hayashi
- Department of Cardiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Takayoshi Kato
- Department of Cardiovascular Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Keita Fujimoto
- Department of Radiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Takatomo Watanabe
- Department of Cardiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Hiroyuki Okura
- Department of Cardiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
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10
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Siracusa C, Carabetta N, Morano MB, Manica M, Strangio A, Sabatino J, Leo I, Castagna A, Cianflone E, Torella D, Andreucci M, Zicarelli MT, Musolino M, Bolignano D, Coppolino G, De Rosa S. Understanding Vascular Calcification in Chronic Kidney Disease: Pathogenesis and Therapeutic Implications. Int J Mol Sci 2024; 25:13096. [PMID: 39684805 DOI: 10.3390/ijms252313096] [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: 10/25/2024] [Revised: 12/04/2024] [Accepted: 12/04/2024] [Indexed: 12/18/2024] Open
Abstract
Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease.
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Affiliation(s)
- Chiara Siracusa
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Nicole Carabetta
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Maria Benedetta Morano
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Marzia Manica
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Antonio Strangio
- Department of Experimental and Clinical Medicine, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Jolanda Sabatino
- Department of Experimental and Clinical Medicine, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Isabella Leo
- Department of Experimental and Clinical Medicine, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Alberto Castagna
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Eleonora Cianflone
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Daniele Torella
- Department of Experimental and Clinical Medicine, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Michele Andreucci
- Department of Health Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Maria Teresa Zicarelli
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Michela Musolino
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Davide Bolignano
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Giuseppe Coppolino
- Department of Health Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
| | - Salvatore De Rosa
- Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy
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11
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Ding UZ, Ooi L, Wu HH, Chinnadurai R. Infective Endocarditis in Patients Receiving Hemodialysis: A Current Review. KIDNEY DISEASES (BASEL, SWITZERLAND) 2024; 10:519-530. [PMID: 39664341 PMCID: PMC11631043 DOI: 10.1159/000540513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 07/20/2024] [Indexed: 12/13/2024]
Abstract
Background Cardiovascular and infective complications are commonly observed in patients receiving hemodialysis (HD) with cardiovascular events and infection-related complications being the first and second leading causes of death. Infective endocarditis (IE) is characterized by inflammation of the endocardium caused by infection, typically affecting the cardiac valves and can be in acute, subacute, or chronic forms. It is a serious complication within the HD population due to their predisposition for both infection and valvular damage. Considering the frailty and burden of comorbidities in those receiving HD, management of IE in the HD population is very challenging. There has been continuous discussion and debate on optimizing the diagnostic and treatment approach of IE in this patient group to improve their clinical outcomes. Currently, reported outcomes are relatively poor and there are updates from numerous guidelines relating to advances in IE management. Summary In this review, we will evaluate the evidence in relation to the epidemiology of HD-associated IE and discuss the important risk factors of IE in patients requiring dialysis. We will also evaluate the current recommendations regarding diagnosis and treatment for suspected or confirmed IE cases amongst HD patients and present the updated data regarding clinical outcomes relating to HD-associated IE. Key Messages The incidence of IE in HD patients is expected to increase going forward as HD becomes more easily accessible alongside an emerging uptake of home HD. A more thorough insight into this topic is required to improve clinical practice relating to IE prevention and management in the HD population, given relatively poor clinical outcomes.
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Affiliation(s)
- UZhe Ding
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford, UK
| | - LiJin Ooi
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford, UK
| | - Henry H.L. Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital and The University of Sydney, Sydney, NSW, Australia
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford, UK
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
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12
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Chen L, Xu R, Xu H, Yang Z, Zhang Y, Li Z, Xia C, Rao L, Guo Y. Myocardial involvement in end-stage renal disease patients with anemia as assessed by cardiovascular magnetic resonance native T1 mapping: An observational study. Medicine (Baltimore) 2024; 103:e39724. [PMID: 39560547 PMCID: PMC11575988 DOI: 10.1097/md.0000000000039724] [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: 01/20/2024] [Accepted: 08/26/2024] [Indexed: 11/20/2024] Open
Abstract
Cardiovascular disease has become to the main cause of death in the patients with end-stage renal disease (ESRD), and anemia is associated with increased cardiovascular morbidity and mortality in these patients. This study aimed to explore the impact of anemia on myocardial fibrosis using T1 mapping technique in patients with ESRD. A total of 128 subjects including 98 ESRD patients (65 with anemia, 33 without anemia) and 30 normal controls were enrolled. All subjects were underwent cardiovascular magnetic resonance to obtain cardiac cine and T1 mapping images. As potential markers of fibrosis, native T1 values and global longitudinal strain derived by feature-tracking technique were compared. Differences between 3 groups were analyzed using one-way analysis of variance. Associations between variables were assessed by Pearson and Spearman correlation coefficient appropriately. An independent association was identified by the multiple stepwise linear regression analysis. Intraclass correlation was applied to assess observer variability. In all ESRD patients, native T1 values were significantly longer than those of normal controls (global T1, 1357 ± 42 ms vs 1275 ± 48 ms, P < .001). Global T1 value in ESRD patients with anemia was significantly higher (1375 ± 36 ms) compared to that in ESRD patients without anemia (1322 ± 25 ms) and normal controls (1275 ± 48 ms), respectively (all P < .001). Global T1 correlated with hemoglobin negatively (R= -0.499, P < .001). Multiple stepwise linear regression analysis presented the anemia is independently associated with global T1 (R = 0.607, P < .001). Global longitudinal strain was remarkably reduced in ESRD patients with anemia in comparison to those without anemia (P < .001). Diffuse myocardial fibrosis could be detected by native T1 mapping in ESRD patients with long-term anemia. Anemia is an important factor in myocardial fibrosis in ESRD patients, and the evaluation of myocardial involvement is worth considering for clinical management.
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Affiliation(s)
- Lin Chen
- Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jinagsu, China
| | - Rong Xu
- Department of Radiology, West China Second University Hospital, Sichuan University, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, China
| | - Huayan Xu
- Department of Radiology, West China Second University Hospital, Sichuan University, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, China
| | - Zhigang Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yi Zhang
- Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Zhenlin Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunchao Xia
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Li Rao
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yingkun Guo
- Department of Radiology, West China Second University Hospital, Sichuan University, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, China
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13
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Ozoe S, Koyama Y, Inagaki M, Tomita S. Rapid growth of calcified amorphous tumor with mitral annulus calcification: a case report. GENERAL THORACIC AND CARDIOVASCULAR SURGERY CASES 2024; 3:39. [PMID: 39517092 PMCID: PMC11533609 DOI: 10.1186/s44215-024-00164-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 08/06/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Calcified amorphous tumor (CAT) of the heart is a rare, non-neoplastic cardiac mass with mitral valves and annuli being the most common sites. The presence of mitral annular calcification (MAC) is associated with an increased risk of stroke or other systemic embolisms. Here, we report a case of CAT showing rapid growth with MAC and investigate the link between the two. CASE PRESENTATION A 71-year-old man presented at our hospital with dyspnea and had been undergoing hemodialysis for 26 years for chronic glomerulonephritis. Transthoracic echocardiography (TTE) revealed moderate mitral stenosis with bulky MAC. Two months later, the patient developed progressive dyspnea, and follow-up TTE revealed a highly mobile mass (8 × 5 mm) attached to the left ventricular (LV) side of the posterior MAC. He underwent surgery because of congestive heart failure and a high risk of embolization. Surgical inspection revealed that the tumor was attached beneath the P3 segment of the mitral valve on the LV side and was removed. When removing the MAC, toothpaste-like contents drained from the encapsulated mass inside the MAC at the P3 segment, where the tumor was located. After reconstructing the posterior mitral annulus defect with a bovine pericardial patch, mitral valve replacement with a mechanical prosthesis, a maze procedure, and left appendage closure were performed. Histopathological examination revealed that the excised tumor contained fibrin and calcium deposits. The mass was diagnosed as a CAT. CONCLUSIONS CAT may be one of the causes of stroke induced by MAC. Routine follow-up echocardiography should be recommended for patients with MAC, especially those undergoing hemodialysis.
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Affiliation(s)
- Satoki Ozoe
- Department of Cardiovascular Surgery, Gifu Heart Canter, 4-14-4 Yabuta minami, Gifu-shi, Gifu, Japan.
| | - Yutaka Koyama
- Department of Cardiovascular Surgery, Gifu Heart Canter, 4-14-4 Yabuta minami, Gifu-shi, Gifu, Japan
| | - Masahiro Inagaki
- Department of Cardiovascular Surgery, Gifu Heart Canter, 4-14-4 Yabuta minami, Gifu-shi, Gifu, Japan
| | - Shinji Tomita
- Department of Cardiovascular Surgery, Gifu Heart Canter, 4-14-4 Yabuta minami, Gifu-shi, Gifu, Japan
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14
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Wang D, Chu X, Cao J, Peng Y. Correlation of serum Klotho, fetuin-A, and MGP levels with coronary artery calcification in maintenance hemodialysis patients. Clinics (Sao Paulo) 2024; 79:100417. [PMID: 39089098 PMCID: PMC11342211 DOI: 10.1016/j.clinsp.2024.100417] [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: 10/18/2023] [Revised: 04/24/2024] [Accepted: 06/11/2024] [Indexed: 08/03/2024] Open
Abstract
OBJECTIVE This study was to investigate the role of serum Klotho, fetuin-A, and Matrix Gla Protein (MGP) in Coronary Artery Calcification (CAC) in patients with Maintenance Hemodialysis (MHD) and their predictive value for CAC. METHODS 100 patients receiving MHD were selected. Serum Klotho, fetuin-A, and MGP levels were detected by ELISA. CAC scores were assessed by coronary CT scan. Multifactor analysis was used to evaluate the risk factors affecting CAC. The ability of serum Klotho, fetuin-A, and MGP levels to diagnose CAC was evaluated by receiver operating characteristic curves. RESULTS Serum Klotho, fetuin-A, and MGP were independent risk factors for CAC. Serum Klotho, fetuin-A, and MGP were valuable in the diagnosis of CAC in MHD patients. CONCLUSION There is a close relationship between Klotho, fetuin-A, and MGP levels in MHD patients and CAC.
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Affiliation(s)
- Dan Wang
- Department of East Hospital Nephrology, Yantaishan Hospital, Yantai City, Shandong Province, China
| | - XiuLin Chu
- Department of Nephrology, The People's Hospital of Xushui, Baoding City, Hebei Province, China
| | - JuHua Cao
- Department of Outpatient, The General Hospital of Western Theater Command of Chinese people's liberation army, Chengdu City, Sichuan Province, China
| | - YunHua Peng
- Department of Nephrology, Dafeng People's Hospital, Yancheng City, JiangSu Province, China.
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15
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Li P, Li Q, Tang M, Hu X, Tian J, Zhang J, Yang C, Zhu B. Associations of phosphorus concentrations with medial arterial calcification in lower-extremity arteries and diabetic foot in people with diabetes: a retrospective cross-sectional study. Cardiovasc Diabetol 2024; 23:275. [PMID: 39061014 PMCID: PMC11282733 DOI: 10.1186/s12933-024-02361-5] [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: 04/14/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. METHODS We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. CONCLUSIONS Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.
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Affiliation(s)
- Peishan Li
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Qingxian Li
- Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
| | - Mingyu Tang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Xingyun Hu
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Jing Tian
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Jianbin Zhang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Chuan Yang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
| | - Baile Zhu
- Zhongshan People's Hospital, Zhongshan, 528403, China.
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16
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Li Q, Li P, Xu Z, Lu Z, Yang C, Ning J. Association of diabetes with cardiovascular calcification and all-cause mortality in end-stage renal disease in the early stages of hemodialysis: a retrospective cohort study. Cardiovasc Diabetol 2024; 23:259. [PMID: 39026232 PMCID: PMC11264609 DOI: 10.1186/s12933-024-02318-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/16/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis. METHODS A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves. RESULTS Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds. CONCLUSIONS In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.
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Affiliation(s)
- Qingxian Li
- Department of Endocrinology, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
| | - Peishan Li
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zigan Xu
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
| | - ZeYuan Lu
- Department of Endocrinology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518033, China
| | - Chuan Yang
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
| | - Jie Ning
- Department of Endocrinology, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China.
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17
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Li X, Du H, Cheng Y, Li X, Gao Q, Chen X. Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification. Nutr Metab Cardiovasc Dis 2024; 34:1696-1702. [PMID: 38664122 DOI: 10.1016/j.numecd.2024.03.013] [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: 07/26/2023] [Revised: 03/02/2024] [Accepted: 03/09/2024] [Indexed: 06/12/2024]
Abstract
BACKGROUND AND AIM The aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. METHODS AND RESULTS A total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0-5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04-3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). CONCLUSIONS High levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).
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Affiliation(s)
- Xuelong Li
- Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
| | - Heng Du
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
| | - Yangyang Cheng
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
| | - Xianliang Li
- Institute of Neuroscience, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Qingchun Gao
- Institute of Neuroscience, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Xiangyan Chen
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
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18
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Sasaki S, Fujisaki K, Nishimura M, Nakano T, Abe M, Hanafusa N, Joki N. Association Between Disturbed Serum Phosphorus Levels and QT Interval Prolongation. Kidney Int Rep 2024; 9:1792-1801. [PMID: 38899225 PMCID: PMC11184388 DOI: 10.1016/j.ekir.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 02/09/2024] [Accepted: 03/04/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation. Methods A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome. Results A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve. Conclusion Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD.
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Affiliation(s)
- Sho Sasaki
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto City, Kyoto, Japan
- Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan
| | | | | | - Toshiaki Nakano
- Department of Medical and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masanori Abe
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Norio Hanafusa
- Department of Blood Purification, Tokyo Women`s Medical University, Tokyo, Japan
| | - Nobuhiko Joki
- Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
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19
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He M, Ren S, Lin Y, Zeng X. Correlation between serum phosphate and all-cause mortality in critically ill patients with coronary heart disease accompanied by chronic kidney disease: a retrospective study using the MIMIC-IV database. Front Cardiovasc Med 2024; 11:1371000. [PMID: 38883990 PMCID: PMC11176493 DOI: 10.3389/fcvm.2024.1371000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/13/2024] [Indexed: 06/18/2024] Open
Abstract
Background The adverse clinical endpoints of cardiovascular and kidney diseases are correlated with increased serum phosphate levels. However, in critically ill patients with coronary heart disease (CHD) accompanied by chronic kidney disease (CKD), the prognostic value of serum phosphate remains unclear. Methods Patients' medical records from the Medical Information Mart for Intensive Care IV database who had concomitant CKD and CHD were classified into four distinct groups in this large retrospective observational cohort study based on the quartiles of serum phosphate levels. Vital status and the duration of hospital and ICU stays within the short-term follow-up periods of 30 and 90 days constituted the primary outcomes. All-cause mortality in the intensive care unit (ICU) and hospital constituted the secondary outcomes. Further, the Cox proportional hazard and restricted cubic spline (RCS) regression models were employed to ascertain how serum phosphate levels correlated with the primary outcomes. In addition, the occurrence rate of the secondary outcomes across the four quartiles was determined utilizing the Kaplan-Meier method. Results Among the total 3,557 patients (67.6% male) included, the hospital and ICU all-cause mortality rates were 14.6% and 10%, separately. Higher quartiles of serum phosphate concentrations were associated with shorter short-term survival rates, as shown by the Kaplan-Meier curves. Additionally, the Cox proportional hazards analysis illustrated that serum phosphate was independently linked to a higher death risk in the hospital [HR, 1.10 (95% CI: 1.03-1.18), P = 0.007] and ICU [HR, 1.14 (95% CI: 1.07-1.22), P < 0.001]. Lastly, the RCS regression models suggested a robust non-linear correlation between serum phosphate concentrations and death risk in the ICU and hospital (both P for non-linearity <0.001). Conclusions The prognostic value of serum phosphate is significant in critically ill patients with CHD accompanied by CKD. Furthermore, serum phosphate is potentially valuable for identifying patients with this concomitant condition.
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Affiliation(s)
- Min He
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Siyu Ren
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yongqi Lin
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaocong Zeng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Guangxi Key Laboratory Base of Precision Medicine in Cardiocerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, Guangxi, China
- School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China
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20
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Yang C, Wei Z, Shi W, Xing J, Zhang X. SNF472: a novel therapeutic agent for vascular calcification and calciphylaxis. J Nephrol 2024; 37:851-863. [PMID: 38512376 DOI: 10.1007/s40620-024-01909-8] [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: 10/16/2023] [Accepted: 01/15/2024] [Indexed: 03/23/2024]
Abstract
Vascular calcification is a common complication in patients with chronic kidney disease (CKD) and is strongly associated with an increased risk of cardiovascular events and all-cause mortality. Calciphylaxis is a specific and life-threatening manifestation of vascular calcifications that usually affects individuals with advanced kidney function impairment or those undergoing dialysis. Currently, the treatment of vascular calcification and calciphylaxis in CKD lacks approved treatments and focuses on controlling risk factors. SNF472, the intravenous formulation of myo-inositol hexaphosphate, is a novel vascular calcification inhibitor currently undergoing phase 3 clinical trials, demonstrating its ability to directly inhibit the formation of calcium and phosphorus crystals, thereby blocking the production and deposition of ectopic calcium. The efficacy and safety of SNF472 in inhibiting vascular calcification have been confirmed in recent clinical studies. This review summarizes the results of studies related to SNF472 to provide a comprehensive overview of its mechanism of action, efficacy, safety, and ongoing clinical studies.
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Affiliation(s)
- Canlin Yang
- Department of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zhiyuan Wei
- Department of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Wen Shi
- Department of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jie Xing
- Department of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiaoliang Zhang
- Department of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
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21
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Merra G, Dominici F, Gualtieri P, Capacci A, Cenname G, Esposito E, Dri M, Di Renzo L, Marchetti M. Role of vitamin K2 in bone-vascular crosstalk. INT J VITAM NUTR RES 2024; 94:143-152. [PMID: 36039403 DOI: 10.1024/0300-9831/a000761] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Vitamin K (VK) is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs). It has been shown to play an important role in the proper calcium deposit at the bone level, hindering that on the vascular walls. The deficiency of this vitamin in European populations is frequent and unknown. It is related to several factors, poor dietary intake, altered intestinal absorption or altered production by bacteria, indicating possible dysbiosis. For Vitamin K2 (VK2), there is currently no official reference daily intake (RDI). However, the effects of VK2 on the improvement of health in cardiovascular diseases, on bone metabolism, on chronic kidney diseases have been the subject of research in recent decades. The microbiota in the gastrointestinal tract plays an important role: Bacteroides are primarily capable of synthetizing very long chain forms of menaquinones and, in addition to the bacteria present in the intestinal flora, VK2 is also produced by bacteria used in food fermentation processes. This review provides an update on the current literature regarding the origin of VK2 and its implications in what is called the "calcium paradox", namely the lack of calcium in the bone and its storage in the wall of the vessel.
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Affiliation(s)
- Giuseppe Merra
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Francesca Dominici
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Paola Gualtieri
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Annunziata Capacci
- Department of Medical and Surgical Sciences, Agostino Gemelli General Hospital Foundation-IRCCS, Rome, Italy
| | - Giuseppe Cenname
- Comando Generale Arma Carabinieri, Direzione di Sanità, Rome, Italy
| | - Ernesto Esposito
- General Directorate, Department of Human Policies of Basilicata Region, Potenza, Italy
| | - Maria Dri
- Department of Surgical Sciences, School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Laura Di Renzo
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Marco Marchetti
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
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22
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Kotsugi M, Nakagawa I, Sasaki H, Okamoto A, Nakase K, Maeoka R, Yokoyama S, Yamada S, Nakase H. Thin Calcification Predicts Lipid Component in Carotid Plaque-Relationship Between Lipid Distribution and Thin Calcification. World Neurosurg 2024; 183:e715-e721. [PMID: 38191057 DOI: 10.1016/j.wneu.2024.01.011] [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: 07/29/2023] [Accepted: 01/02/2024] [Indexed: 01/10/2024]
Abstract
BACKGROUND Accurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS. METHODS Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS. RESULTS Strong negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P < 0.001) and lipid core burden index (LCBI) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008). CONCLUSIONS Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.
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Affiliation(s)
- Masashi Kotsugi
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Ichiro Nakagawa
- Departments of Neurosurgery, Nara Medical University, Nara, Japan.
| | - Hiromitsu Sasaki
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Ai Okamoto
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Kenta Nakase
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Ryosuke Maeoka
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Shohei Yokoyama
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Shuichi Yamada
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
| | - Hiroyuki Nakase
- Departments of Neurosurgery, Nara Medical University, Nara, Japan
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23
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Perelló J, Alberti J, Torres JV, Ferrer MD, Perez MM, Bassissi F, Gold A, Raggi P, Chertow GM, Salcedo C. Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification. Front Pharmacol 2024; 15:1325186. [PMID: 38384289 PMCID: PMC10879272 DOI: 10.3389/fphar.2024.1325186] [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: 10/24/2023] [Accepted: 01/24/2024] [Indexed: 02/23/2024] Open
Abstract
Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52 weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple Emax model for maximum concentration (Cmax) and PD effect, and linear and non-linear Emax models for exposure-efficacy among individual average Cmax and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo (n = 15), 300 mg (n = 20), or 600 mg (n = 20), average Cmax across visits was not quantifiable (<0.76 μM), 15 μM, and 46 μM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a Cmax ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple Emax models described 80% maximal effect at exposures >21.9 µM and a plateau in exposure-efficacy above the third quartile of Cmax (≥32 µM). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028.
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Affiliation(s)
- Joan Perelló
- Sanifit Therapeutics S.A., Palma, Spain
- Department of Chemistry, University of the Balearic Islands, Palma, Spain
| | | | | | - Miguel D. Ferrer
- Sanifit Therapeutics S.A., Palma, Spain
- Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma, Spain
| | | | | | - Alex Gold
- Sanifit Therapeutics S.A., Palma, Spain
- Department of Medicine, Stanford University, Palo Alto, CA, United States
| | - Paolo Raggi
- Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Glenn M. Chertow
- Department of Medicine, Stanford University, Palo Alto, CA, United States
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24
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Rafiee MJ, Bandegi P, Taylor JL. Extensive myocardial calcifications in a dialysis patient: A porcelain heart manifesting with abdominal pain. Radiol Case Rep 2024; 19:523-530. [PMID: 38044898 PMCID: PMC10686893 DOI: 10.1016/j.radcr.2023.10.081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/28/2023] [Accepted: 10/30/2023] [Indexed: 12/05/2023] Open
Abstract
This case report describes a 41-year-old male patient with chronic kidney disease on peritoneal dialysis presenting with upper abdominal pain and mild thigh numbness. CT chest demonstrated extensive myocardial calcifications and left atrial thrombus. This case emphasizes the clinical relevance of myocardial calcifications, especially in patients with end-stage renal disease. It also highlights the potential association between these calcifications and complications such as atrial fibrillation and thromboembolic events. The findings emphasize the need for diagnostic vigilance and an improved understanding of the pathophysiology of myocardial calcifications in the context of renal disease.
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Affiliation(s)
- Moezedin Javad Rafiee
- Department of Diagnostic Radiology, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
- Research Institute, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
| | - Pouya Bandegi
- Department of Diagnostic Radiology, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
| | - Jana Lyn Taylor
- Research Institute, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
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25
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Kojima S, Usui N, Shigetake M, Uehata A, Inatsu A, Ando S, Matsuzawa R, Suzuki Y, Nakata J, Tsuchiya T, Hisadome H, Mawatari T, Tsubaki A. Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients. Nephrol Dial Transplant 2024; 39:286-296. [PMID: 37458763 DOI: 10.1093/ndt/gfad169] [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: 12/20/2022] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.
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Affiliation(s)
- Sho Kojima
- Department of Rehabilitation, Kisen Hospital, Tokyo, Katsushika-ku, Japan
- Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, Niigata-city, Niigata, Japan
| | - Naoto Usui
- Department of Rehabilitation, Kisen Hospital, Tokyo, Katsushika-ku, Japan
- Department of Nephrology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Masato Shigetake
- Department of Radiology, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Akimi Uehata
- Division of Cardiology, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Akihito Inatsu
- Division of Nephrology, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Shuji Ando
- Department of Information Sciences, Tokyo University of Science, Noda-city, Chiba, Japan
| | - Ryota Matsuzawa
- Department of Physical Therapy, School of Rehabilitation, Kobe-city, Hyogo Medical University, Hyogo, Japan
| | - Yusuke Suzuki
- Department of Nephrology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Junichiro Nakata
- Department of Nephrology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Takahiko Tsuchiya
- Division of Internal Medicine, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Hideki Hisadome
- Division of Cardiology, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Takayuki Mawatari
- Division of Internal Medicine, Kisen Hospital, Katsushika-ku, Tokyo, Japan
| | - Atsuhiro Tsubaki
- Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, Niigata-city, Niigata, Japan
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26
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Zaslow SJ, Oliveira-Paula GH, Chen W. Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights. Int J Mol Sci 2024; 25:1155. [PMID: 38256228 PMCID: PMC10816532 DOI: 10.3390/ijms25021155] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 01/24/2024] Open
Abstract
Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions.
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Affiliation(s)
- Shari J. Zaslow
- Department of Medicine, Nephrology Division, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT 05405, USA
| | - Gustavo H. Oliveira-Paula
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Wei Chen
- Department of Medicine, Nephrology Division, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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27
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Yang KJ, Fu HY, Chang CJ, Wang TC, Wang CH, Chou NK, Wu IH, Hsu RB, Huang SC, Yu HY, Chen YS, Chi NH. Long-term outcomes of mitral valve replacement in dialysis patients: evidence from a nationwide database. Int J Surg 2023; 109:3778-3787. [PMID: 37678297 PMCID: PMC10720870 DOI: 10.1097/js9.0000000000000684] [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: 05/30/2023] [Accepted: 08/04/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND To compare the late outcomes between mechanical and bioprostheses after isolated mitral valve replacement (MVR) in dialysis-dependent patients. METHODS A nationwide propensity-matched retrospective cohort study was conducted involving dialysis patients who underwent primary mitral replacement between 2001 and 2018. Ten-year postoperative outcomes were compared between mitral bioprosthesis and mechanical prosthesis using the Cox proportional hazard model and restricted mean survival time (RMST). RESULTS The all-cause mortality was 20.8 and 13.0 events per 100 person-years, with a 10-year RMST of 7.40 and 7.31 years for bioprosthesis and mechanical prosthesis, respectively. Major bleeding was the most common adverse event for both bioprosthesis and mechanical prosthesis, with an incidence rate of 19.5 and 19.1 events per 100 person-years, respectively. The incidence of valve reoperation was higher among those who received bioprosthesis (0.55 events per 100 person-years). After 1:1 matching, the all-cause mortality was 15.45 and 14.54 events per 100 person-years for bioprosthesis and mechanical prosthesis, respectively. The RMST at 10 years was comparable between the two groups after matching (5.10 years for bioprosthesis vs. 4.59 years for mechanical prosthesis), with an RMST difference of -0.03. Further, no difference was observed in the incidence of major adverse valve-related events between bioprosthesis and mechanical valves. However, bioprosthesis was associated with a higher incidence of mitral valve reoperation among all major adverse events (RMST difference -0.24 years, 95% CI -0.48 to -0.01, P =0.047). CONCLUSIONS This study found no association between valve selection and long-term survival outcomes in dialysis patients after MVR. However, bioprosthetic valves may be associated with a slightly higher incidence of reoperation, while other valve-related adverse events, including major bleeding and stroke, were comparable between the two types of prostheses.
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Affiliation(s)
- Kelvin J. Yang
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Hsun-Yi Fu
- Department of Cardiovascular Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu
| | - Chia-Jui Chang
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University
- Department of Pharmacy, National Taiwan University Cancer Center
| | - Ting-Chuan Wang
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Chih-Hsien Wang
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Nai-Kuan Chou
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - I-Hui Wu
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Ron-Bin Hsu
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Shu-Chien Huang
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Hsi-Yu Yu
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Yih-Sharng Chen
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
| | - Nai-Hsin Chi
- Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei
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28
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Saito T, Shiono Y, Nagamine S, Fujita M, Okimoto T, Okabe T, Keida T, Ohira H, Kawase Y, Murata N, Yamashita J, Matsuo A, Fujita H, Takashima H, Amano T, Hokama Y, Matsuo H, Tanaka N, Akasaka T. Prognostic Values of Fractional Flow Reserve Based on Clinical Outcomes in Patients on Chronic Hemodialysis. Am J Cardiol 2023; 207:441-447. [PMID: 37797551 DOI: 10.1016/j.amjcard.2023.08.135] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/17/2023] [Accepted: 08/20/2023] [Indexed: 10/07/2023]
Abstract
The fractional flow reserve (FFR) cut-off values of 0.75 or 0.8 have been widely used; however, whether they apply to patients on hemodialysis remains unknown. We aimed to investigate the cut-off value of FFR associated with clinical outcomes in patients on hemodialysis. Using the Japanese multicenter registry, we analyzed data of patients on hemodialysis with measured FFR between January 2010 and December 2016. Survival classification and regression tree analysis for the composite primary outcome of cardiovascular mortality, myocardial infarction, and target vessel revascularization revealed a threshold FFR of 0.83. Multivariate Cox regression analyses were performed for the clinical outcomes. Additionally, the primary outcome was analyzed using propensity score matching by dividing the patients into complete and incomplete revascularization groups according to the presence of residual lesions with an FFR of ≤0.83 after the intervention. Of the 212 included patients, 112 (52.8%) had lesions with an FFR of ≤0.83. After adjusting for confounders, an FFR of ≤0.83 was associated with a higher risk for the primary outcome (adjusted hazard ratio 2.01, 95% confidence interval 1.11 to 3.66, p = 0.021). Propensity score matching showed that complete revascularization for lesions with an FFR of ≤0.83 was associated with a reduced risk for the primary outcome compared with incomplete revascularization (hazard ratio 0.38, 95% confidence interval 0.20 to 0.71, log-rank p = 0.0016). In conclusion, an FFR of ≤0.83 was an independent predictor of clinical events in patients on hemodialysis. Furthermore, complete revascularization was associated with better clinical outcomes. Thus, this population may require a distinct FFR cut-off value.
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Affiliation(s)
- Tetsuya Saito
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan.
| | - Yasutsugu Shiono
- Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan
| | - Sho Nagamine
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan
| | - Masaki Fujita
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan
| | | | - Teruo Okabe
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan
| | - Takehiko Keida
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan
| | - Hiroshi Ohira
- Department of Cardiology, Edogawa Hospital, Tokyo, Japan
| | - Yoshiaki Kawase
- Department of Cardiovascular Medicine. Gifu Heart Center, Gifu, Japan
| | - Naotaka Murata
- Department of Cardiology, Tokyo Medical University, Tokyo, Japan
| | - Jun Yamashita
- Department of Cardiology, Tokyo Medical University, Tokyo, Japan
| | - Akiko Matsuo
- Department of Cardiology, Kyoto City Hospital, Kyoto, Japan
| | - Hiroshi Fujita
- Department of Cardiology, Kyoto City Hospital, Kyoto, Japan
| | | | - Tetsuya Amano
- Department of Cardiology, Aichi Medical University, Aichi, Japan
| | - Yohei Hokama
- Department of Cardiology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
| | - Hitoshi Matsuo
- Department of Cardiovascular Medicine. Gifu Heart Center, Gifu, Japan
| | - Nobuhiro Tanaka
- Department of Cardiology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
| | - Takashi Akasaka
- Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan
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Iyengar A, Song C, Weingarten N, Rekhtman D, Herbst DA, Shin M, Helmers MR, Atluri P. Prosthesis Choice in Dialysis Patients Undergoing Mitral Valve Replacement. Ann Thorac Surg 2023; 116:963-970. [PMID: 37245789 DOI: 10.1016/j.athoracsur.2023.05.015] [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] [Received: 11/23/2022] [Revised: 04/26/2023] [Accepted: 05/16/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND Patients with renal disease on dialysis have significant comorbidity limiting life expectancy; however, these patients may experience accelerated prosthetic valve degeneration. The purpose of this study was to examine the impact of prosthesis choice on outcomes in dialysis patients undergoing mitral valve replacement (MVR) at our high-volume academic center. METHODS Adults undergoing MVR were retrospectively reviewed between January 2002 and November 2019. Patients were included if they had documented renal failure and dialysis requirements before presentation. Patients were stratified by mechanical vs bioprosthetic prosthesis. Death and recurrent severe valve failure (3+ or greater) or redo mitral operation were used as primary outcomes. RESULTS There were 177 dialysis patients identified who underwent MVR. Of these, 118 (66.7%) received bioprosthetic valves, whereas 59 (33.3%) received mechanical valves. Those who received mechanical valves were younger (48 vs 61 years; P < .001) and had less diabetes (32% vs 51%; P = .019). Prevalence of endocarditis and atrial fibrillation was similar. Postoperative length of stay was not different between groups. Risk-adjusted hazard for 5-year mortality was similar between groups (P = .668). Early mortality was high, with both groups having <50% actuarial survival at 2 years. No differences were noted in rates of structural valve deterioration or reintervention. More stroke events were noted on follow-up in patients receiving mechanical valves (15% vs 6%; P = .041). Endocarditis was the leading reason for reintervention; 4 patients received repeated surgery for bioprosthetic valve failure. CONCLUSIONS MVR in dialysis patients carries significant morbidity and increased midterm mortality. Decreased life expectancy should be considered in the tailoring of prosthesis choice to dialysis-dependent patients.
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Affiliation(s)
- Amit Iyengar
- Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Cindy Song
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Noah Weingarten
- Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - David Rekhtman
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - David A Herbst
- Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Max Shin
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mark R Helmers
- Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Pavan Atluri
- Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
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Nishizawa Y, Miyata S, Tosaka M, Hirasawa E, Hosoda Y, Horimoto A, Omae K, Ito K, Nagano N, Hoshino J, Ogawa T. Serum oxalate concentration is associated with coronary artery calcification and cardiovascular events in Japanese dialysis patients. Sci Rep 2023; 13:18558. [PMID: 37899362 PMCID: PMC10613608 DOI: 10.1038/s41598-023-45903-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 10/25/2023] [Indexed: 10/31/2023] Open
Abstract
Coronary artery calcification (CAC) is associated with cardiovascular disease (CVD). CAC might contain calcium oxalate, and a high serum oxalate (SOx) concentration is associated with cardiovascular mortality in dialysis patients. We assessed the associations between SOx and CAC or CVD events in Japanese hemodialysis patients. This cross-sectional and retrospective cohort study was done in 2011. Seventy-seven hemodialysis patients' Agatston CAC score was measured, and serum samples were collected. SOx concentrations were measured in 2021 by using frozen samples. Also, new-onset CVD events in 2011-2021 were retrospectively recorded. The association between SOx concentration and CAC score ≥ 1000, and new-onset CVD events were examined. Median SOx concentration and CAC score were 266.9 (229.5-318.5) µmol/L and 912.5 (123.7-2944), respectively. CAC score ≥ 1000 was associated with SOx [adjusted odds ratio (OR) 1.01, 95% confidence interval (CI), 1.00-1.02]. The number of new-onset CVD events was significantly higher in patients with SOx ≥ median value [hazard ratio (HR) 2.71, 95% CI 1.26-6.16]. By Cox proportional hazard models, new-onset CVD events was associated with SOx ≥ median value (adjusted HR 2.10, 95% CI 0.90-4.91). SOx was associated with CAC score ≥ 1000 and new-onset CVD events in Japanese hemodialysis patients.
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Affiliation(s)
- Yoko Nishizawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan.
- Teikyo University Graduate School of Public Health, Itabashi, Tokyo, Japan.
| | - Satoshi Miyata
- Teikyo University Graduate School of Public Health, Itabashi, Tokyo, Japan
| | - Mai Tosaka
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
| | - Eriko Hirasawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
| | - Yumi Hosoda
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
| | - Ai Horimoto
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
| | - Kiyotsugu Omae
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
| | - Kyoko Ito
- Kidney Disease and Dialysis Center, Hidaka Hospital, Hidaka-kai, Takasaki, Gunma, Japan
| | - Nobuo Nagano
- Kidney Disease and Dialysis Center, Hidaka Hospital, Hidaka-kai, Takasaki, Gunma, Japan
| | - Junichi Hoshino
- Department of Nephrology, Tokyo Women's Medical University, Shinjuku, Tokyo, Japan
| | - Tetsuya Ogawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi, Tokyo, 123-8558, Japan
- Kidney Disease and Dialysis Center, Hidaka Hospital, Hidaka-kai, Takasaki, Gunma, Japan
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Arabi Z, Tawhari MH, Al Rajih HS, Youssouf TM, Abdulgadir MY. Findings of Cardiovascular Workup of Kidney Transplant Candidates: A Retrospective Study of a Single-Center in Saudi Arabia. Int J Nephrol 2023; 2023:4653069. [PMID: 37854308 PMCID: PMC10581843 DOI: 10.1155/2023/4653069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/20/2023] [Accepted: 09/22/2023] [Indexed: 10/20/2023] Open
Abstract
Background There are limited data about the prevalence of cardiovascular (CV) risk factors and the findings of CV workup among kidney transplant (KTx) recipients (KTRs) in Saudi Arabia. Methods A single-center retrospective study of KTRs who underwent KTx from 2017 to 2020 was performed. We reviewed the prevalence of CV risk factors and the results of the pre-KTx CV workup which was derived from the American Heart Association guidelines. Results We included 254 KTRs. The mean age was 43.1 ± 15.9 years, and 55.5% were men and 79.5% were living-donor KTRs. Pre-emptive KTx was 9.8%, peritoneal dialysis was 11.8%, and hemodialysis was 78.3% (arteriovenous fistula: 33.1% versus hemodialysis catheter: 66.9%). The mean dialysis vintage was 4.8 ± 3.3 years for deceased-donor KTRs versus 2.4 ± 2.6 years for living-donor KTRs. CV risk factors were hypertension: 76%, diabetes: 40.6% (type 1 : 25.2% versus type 2 : 74.7%), hyperlipidemia (low-density lipoprotein >2.6 mmol/L): 40.2%, coronary artery disease (CAD): 12.6%, smoking: 9.1%, peripheral vascular disease: 2.8%, and cerebral vascular disease: 2.4%. The prevalence of obesity stage 1 was 19.7% and obesity stage 2 was 4%. Left ventricular hypertrophy was present in 38.5%. The ejection fraction was abnormal (<55%) in 22%. Abnormal wall motion was present in 34 patients (13.4%). A cardiac (PET-CT) stress test was conducted on 129 patients (50.8%) which showed abnormal perfusion in 37 patients (28.7%). Out of those who required PET-CT, 18.6% had a coronary artery calcium scoring (CACS) of more than 400, 41.8% had a CACS of zero, 29.4% had a CACS of 1-100, and 14.7% had a CACS of 100-400. Coronary angiogram was required in only 41 patients (16.1%), 12 (29.3%) required coronary interventions, 25 (61%) were treated medically, and 4 (9.8%) did not have any CAD. CT scans of pelvic arteries were performed in 118 patients (46.5%). It showed moderate or severe calcifications in only 7 patients (5.9%), whereas it was normal in 97 patients (82.2%), or it showed only mild calcifications in 14 patients (11.9%). Conclusion This study outlines the prevalence of CV risk factors and the findings of the pretransplant CV workup among KTx candidates who underwent KTx. Multicenter national studies will be helpful to validate the generalizability of these findings.
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Affiliation(s)
- Ziad Arabi
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed H. Tawhari
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Haneen S. Al Rajih
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Talha M. Youssouf
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohamad Y. Abdulgadir
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Hamiduzzaman A, Wu R, Murray V, Kalantar-Zadeh K, Streja E, Sy J. Comparing the Fried frailty phenotype versus the Veterans Affairs frailty index among dialysis dependent patients. Hemodial Int 2023; 27:444-453. [PMID: 37318050 DOI: 10.1111/hdi.13101] [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: 03/01/2023] [Revised: 05/15/2023] [Accepted: 05/23/2023] [Indexed: 06/16/2023]
Abstract
INTRODUCTION Frailty in dialysis patients is a modifiable disease state which can increase mortality if left untreated but remains underdiagnosed as frailty evaluations can be arduous or time consuming. We evaluate the agreement between a clinical frailty construct (Fried frailty phenotype, FFP) against and an electronic health record-based Veterans Affairs Frailty Index (VAFI) and their association with mortality. METHODS A retrospective cohort analysis of 764 participants from the ACTIVE/ADIPOSE study was performed. Frailty as measured by VAFI and FFP was obtained and Kappa statistic estimating concordance between the two scores were calculated. Differences in mortality risk were analyzed according to presence or absence of frailty. FINDINGS When assessing agreement between the VAFI and FFP, the kappa statistic was 0.09 (95% confidence interval [CI] 0.02-0.16) suggesting a low level of agreement. Frailty was independently associated with higher mortality risk (hazards ratio [HR] 1.40-1.42 in fully adjusted models depending upon frailty construct). Discordantly frail patients by construct had a higher risk of mortality though this was not statistically significant after adjustment. However, concordantly frail patients had much higher mortality risk compared to concordantly nonfrail (adjusted HR 2.08, 95% CI 1.44-3.01). DISCUSSION Poor agreement between constructs is likely reflective of the multifactorial definition of frailty. While further longitudinal studies are needed to determine if the VAFI would be beneficial in the reassessment of frailty, it may be beneficial as a cue for further frailty testing (e.g., with FFP) with the combination of multiple frail constructs providing improved prognostic information.
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Affiliation(s)
- Anum Hamiduzzaman
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
- Veterans Affairs Long Beach Healthcare System, Division of Nephrology, Long Beach, California, USA
| | - Ruoxue Wu
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
| | - Victoria Murray
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
- Veterans Affairs Long Beach Healthcare System, Division of Nephrology, Long Beach, California, USA
| | - Elani Streja
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
- Veterans Affairs Long Beach Healthcare System, Division of Nephrology, Long Beach, California, USA
| | - John Sy
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, California, USA
- Veterans Affairs Long Beach Healthcare System, Division of Nephrology, Long Beach, California, USA
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Cejka D, Wakolbinger-Habel R, Zitt E, Fahrleitner-Pammer A, Amrein K, Dimai HP, Muschitz C. [Diagnosis and treatment of osteoporosis in patients with chronic kidney disease : Joint guidelines of the Austrian Society for Bone and Mineral Research (ÖGKM), the Austrian Society of Physical and Rehabilitation Medicine (ÖGPMR) and the Austrian Society of Nephrology (ÖGN)]. Wien Med Wochenschr 2023; 173:299-318. [PMID: 36542221 PMCID: PMC10516794 DOI: 10.1007/s10354-022-00989-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 11/09/2022] [Indexed: 12/24/2022]
Abstract
DEFINITION AND EPIDEMIOLOGY Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T‑score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T‑score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C). DIAGNOSIS AND RISK STRATIFICATION OF OSTEOPOROSIS IN CKD Densitometry (using dual X‑ray absorptiometry, DXA): low T‑score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T‑score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m2) or CKD 5D (dialysis). SPECIFIC TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CKD Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m2): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m2) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C). PHYSICAL MEDICINE AND REHABILITATION Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B).
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Affiliation(s)
- Daniel Cejka
- Abteilung für Innere Medizin III, Nieren- und Hochdruckerkrankungen, Transplantationsmedizin, Rheumatologie, Akutgeriatrie, Ordensklinikum Linz – Krankenhaus der Elisabethinen, Fadingerstr. 1, 4020 Linz, Österreich
| | - Robert Wakolbinger-Habel
- Department of Physical and Rehabilitation Medicine (PRM), Vienna Healthcare Group – Clinic Donaustadt, Langobardenstr. 122, 1220 Wien, Österreich
| | - Emanuel Zitt
- Department of Internal Medicine 3 (Nephrology and Dialysis), Feldkirch Academic Teaching Hospital, Feldkirch, Österreich
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Österreich
- Agency for Preventive and Social Medicine (aks), Bregenz, Österreich
| | - Astrid Fahrleitner-Pammer
- Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Österreich
| | - Karin Amrein
- Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Österreich
| | - Hans Peter Dimai
- Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Österreich
| | - Christian Muschitz
- Medical Department II – VINFORCE, St. Vincent Hospital Vienna (Barmherzige Schwestern Krankenhaus Wien), Stumpergasse 13, 1060 Wien, Österreich
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Echefu G, Stowe I, Burka S, Basu-Ray I, Kumbala D. Pathophysiological concepts and screening of cardiovascular disease in dialysis patients. FRONTIERS IN NEPHROLOGY 2023; 3:1198560. [PMID: 37840653 PMCID: PMC10570458 DOI: 10.3389/fneph.2023.1198560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 08/10/2023] [Indexed: 10/17/2023]
Abstract
Dialysis patients experience 10-20 times higher cardiovascular mortality than the general population. The high burden of both conventional and nontraditional risk factors attributable to loss of renal function can explain higher rates of cardiovascular disease (CVD) morbidity and death among dialysis patients. As renal function declines, uremic toxins accumulate in the blood and disrupt cell function, causing cardiovascular damage. Hemodialysis patients have many cardiovascular complications, including sudden cardiac death. Peritoneal dialysis puts dialysis patients with end-stage renal disease at increased risk of CVD complications and emergency hospitalization. The current standard of care in this population is based on observational data, which has a high potential for bias due to the paucity of dedicated randomized clinical trials. Furthermore, guidelines lack specific guidelines for these patients, often inferring them from non-dialysis patient trials. A crucial step in the prevention and treatment of CVD would be to gain better knowledge of the influence of these predisposing risk factors. This review highlights the current evidence regarding the influence of advanced chronic disease on the cardiovascular system in patients undergoing renal dialysis.
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Affiliation(s)
- Gift Echefu
- Division of Cardiovascular Medicine, The University of Tennessee Health Science Center, Memphis, TN, United States
| | - Ifeoluwa Stowe
- Department of Internal Medicine, Baton Rouge General Medical Center, Baton Rouge, LA, United States
| | - Semenawit Burka
- Department of Internal Medicine, University of Texas Rio Grande Valley, McAllen, TX, United States
| | - Indranill Basu-Ray
- Department of Cardiology, Memphis Veterans Affairs (VA) Medical Center, Memphis, TN, United States
| | - Damodar Kumbala
- Nephrology Division, Renal Associates of Baton Rouge, Baton Rouge, LA, United States
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Haroon S, Davenport A, Ling LH, Tai BC, Teo LLS, Schurgers L, Chen Z, Shroff R, Fischer DC, Khatri P, Low S, Tan JN, Chua HR, Teo BW, Ong CC, Subramanian S, Yeo XE, Wong WK, Lau TWL. Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK). Kidney Int Rep 2023; 8:1741-1751. [PMID: 37705910 PMCID: PMC10496082 DOI: 10.1016/j.ekir.2023.06.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 05/03/2023] [Accepted: 06/12/2023] [Indexed: 09/15/2023] Open
Abstract
Introduction Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 μg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50-1.94). Conclusion Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.
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Affiliation(s)
- Sabrina Haroon
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Andrew Davenport
- University College London Center for Nephrology, Royal Free Hospital, University College London, UK
| | - Lieng-Hsi Ling
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Bee-Choo Tai
- Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore
| | - Lynette-Li-San Teo
- Department of Diagnostic Imaging, National University Hospital, Singapore
| | - Leon Schurgers
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands
| | - Zhaojin Chen
- Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rukshana Shroff
- UCL Great Ormond Street Hospital for Children NHS Foundation Trust, and Institute of Child Health, London, UK
| | | | - Priyanka Khatri
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Sanmay Low
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Jia-Neng Tan
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Horng-Ruey Chua
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Boon-Wee Teo
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Ching-Ching Ong
- Department of Diagnostic Imaging, National University Hospital, Singapore
| | - Srinivas Subramanian
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Xi-Er Yeo
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Weng-Kin Wong
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
| | - Titus-Wai-Leong Lau
- Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore
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Krishnasamy R, Viecelli AK. Vitamin K in CKD: A Game-Changer or By-Stander. Kidney Int Rep 2023; 8:1711-1713. [PMID: 37705911 PMCID: PMC10496061 DOI: 10.1016/j.ekir.2023.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 07/24/2023] [Indexed: 09/15/2023] Open
Affiliation(s)
- Rathika Krishnasamy
- Department of Nephrology, Sunshine Coast University Hospital, Queensland Australia
- Australasian Kidney Trials Network, University of Queensland, Brisbane, Queensland, Australia
| | - Andrea K. Viecelli
- Australasian Kidney Trials Network, University of Queensland, Brisbane, Queensland, Australia
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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Wang J, Xiao J, Wang R, Wang D. Influencing factors of cardiac valve calcification (CVC) in patients with chronic kidney disease and the impact of CVC on long-term prognosis: a single-center retrospective study. PeerJ 2023; 11:e15569. [PMID: 37404480 PMCID: PMC10317020 DOI: 10.7717/peerj.15569] [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: 11/25/2022] [Accepted: 05/25/2023] [Indexed: 07/06/2023] Open
Abstract
Objective To investigate the effect of cardiac valve calcification (CVC) on the prognosis of patients with chronic kidney disease (CKD). Methods A total of 343 CKD patients were retrospectively analyzed, and divided into two groups according to the presence or absence of cardiac valve calcification. All patients were followed until death, loss to follow-up, or the end point of the study (December 2021). Results The incidence of CVC among the 343 CKD patients was 29.7%, including 21 cases of mitral valve calcification, 63 cases of aortic valve calcification, and 18 cases of mitral valve combined with aortic valve calcification. The incidence of CVC in CKD stages 1-2 was 0.3%, 5.2% in CKD stages 3-4, and 24.2% in CKD stage 5 (P < 0.05). Advanced age, higher serum albumin, higher cystatin C and lower uric acid levels were all associated with a higher risk of CVC. After six years of follow-up, 77 patients (22.4%) died. The causes of death were cardiovascular and cerebrovascular diseases in 36 cases (46.7%), infection in 29 cases (37.7%), gastrointestinal bleeding in nine cases (11.7%), and "other" in the remaining three cases (3.9%). A Kaplan Meier survival analysis showed that the overall survival rate of patients with CVC was lower than that of patients without CVC. Conclusion The incidence of CVC, mainly aortic calcification, is high in patients with CKD. Advanced age, higher serum albumin and higher cystatin C levels were associated with a higher risk of CVC. Hyperuricemia was associated with a lower risk of CVC. The overall survival rate of patients with CVC was lower than that of patients without CVC.
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Affiliation(s)
- Ju Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Jianping Xiao
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Ruifeng Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Deguang Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
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Arabi Z, Tawhari MH, Rajih HSA, Youssouf TM, Abdulgadir MY. Findings of Cardiovascular Workup of Kidney Transplant Candidates: A Retrospective Study of a Single-Center in Saudi Arabia.. [DOI: 10.21203/rs.3.rs-3030184/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Abstract
Background: There are limited data about the prevalence of cardiovascular (CV) risk factors and the findings of CV workup among kidney transplant (KTx) recipients (KTRs) in Saudi Arabia.
Method: A single-center retrospective study of KTRs who underwent KTx from 2017 to 2020. We reviewed the prevalence of CV risk factors and the results of the pre-KTx CV workup which was derived from the American Heart Association guidelines.
Results: We included 254 KTRs. The mean age was 43.1±15.9 years, 55.5% were men and 79.5% were living-donor KTRs. Pre-emptive KTx was 9.8%, peritoneal dialysis: 11.8% and hemodialysis: 78.3% (arteriovenous fistula: 33.1% versus hemodialysis catheter: 66.9%). Mean dialysis vintage was 4.8±3.3 years for deceased-donor KTRs versus 2.4±2.6 years for living-donor KTRs.
CV risk factors were hypertension: 76%, diabetes: 40.6% (type 1: 25.2% versus type 2: 74.7%), hyperlipemia (low-density lipoprotein> 2.6 mmol/L): 40.2%, coronary artery disease (CAD): 12.6%, smoking: 9.1%, peripheral vascular disease: 2.8%, and cerebral vascular disease: 2.4%. The prevalence of obesity stage 1 was 19.7% and obesity stage 2 was 4%.
Left ventricular hypertrophy was present in 38.5%. Ejection fraction was abnormal (<55%) in 22%. Abnormal wall motion was present in 34 patients (13.4%). Cardiac (PET-CT) stress test was indicated in 129 patients (50.8%) and showed abnormal perfusion in 37 patients (28.7%). Out of those who required PET-CT, 18.6% had coronary artery calcium scoring (CACS) more than 400, 41.8 had CACS of zero, 29.4% had CACS of 1-100, and 14.7% had CACS of 100-400.
Coronary angiogram was required in only 41 patients (16.1%), 12 (29.3%) required coronary interventions, 25 (61%) were treated medically, and 4 (9.8%) did not have any CAD.
CT scans of pelvic arteries were performed in 118 patients (46.5%). It showed moderate or severe calcifications in only 7 patients (5.9%), whereas it was normal in 97 patients (82.2%), or it showed only mild calcifications in 14 patients (11.9%).
Conclusion:
This study outlines the prevalence of CV risk factors and the findings of the pretransplant CV workup among KTx candidates who underwent KTx. Multicenter national studies will be helpful to validate the generalizability of these findings.
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Dai Z, Zhang X. Pathophysiology and Clinical Impacts of Chronic Kidney Disease on Coronary Artery Calcification. J Cardiovasc Dev Dis 2023; 10:jcdd10050207. [PMID: 37233174 DOI: 10.3390/jcdd10050207] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/05/2023] [Accepted: 05/06/2023] [Indexed: 05/27/2023] Open
Abstract
The global prevalence of chronic kidney disease (CKD) has increased in recent years. Adverse cardiovascular events have become the main cause of life-threatening events in patients with CKD, and vascular calcification is a risk factor for cardiovascular disease. Vascular calcification, especially coronary artery calcification, is more prevalent, severe, rapidly progressive, and harmful in patients with CKD. Some features and risk factors are unique to vascular calcification in patients with CKD; the formation of vascular calcification is not only influenced by the phenotypic transformation of vascular smooth muscle cells, but also by electrolyte and endocrine dysfunction, uremic toxin accumulation, and other novel factors. The study on the mechanism of vascular calcification in patients with renal insufficiency can provide a basis and new target for the prevention and treatment of this disease. This review aims to illustrate the impact of CKD on vascular calcification and to discuss the recent research data on the pathogenesis and factors involved in vascular calcification, mainly focusing on coronary artery calcification, in patients with CKD.
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Affiliation(s)
- Zhuoming Dai
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Xiangyu Zhang
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, China
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Abstract
Patients with chronic kidney disease (CKD) exhibit tremendously elevated risk for cardiovascular disease, particularly ischemic heart disease, due to premature vascular and cardiac aging and accelerated ectopic calcification. The presence of cardiovascular calcification associates with increased risk in patients with CKD. Disturbed mineral homeostasis and diverse comorbidities in these patients drive increased systemic cardiovascular calcification in different manifestations with diverse clinical consequences, like plaque instability, vessel stiffening, and aortic stenosis. This review outlines the heterogeneity in calcification patterning, including mineral type and location and potential implications on clinical outcomes. The advent of therapeutics currently in clinical trials may reduce CKD-associated morbidity. Development of therapeutics for cardiovascular calcification begins with the premise that less mineral is better. While restoring diseased tissues to a noncalcified homeostasis remains the ultimate goal, in some cases, calcific mineral may play a protective role, such as in atherosclerotic plaques. Therefore, developing treatments for ectopic calcification may require a nuanced approach that considers individual patient risk factors. Here, we discuss the most common cardiac and vascular calcification pathologies observed in CKD, how mineral in these tissues affects function, and the potential outcomes and considerations for therapeutic strategies that seek to disrupt the nucleation and growth of mineral. Finally, we discuss future patient-specific considerations for treating cardiac and vascular calcification in patients with CKD-a population in need of anticalcification therapies.
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Affiliation(s)
- Joshua D. Hutcheson
- Department of Biomedical Engineering, Florida International University, Miami, FL (J.D.H.)
| | - Claudia Goettsch
- Department of Internal Medicine I, Division of Cardiology, Medical Faculty, RWTH Aachen University, Germany (C.G.)
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Combi Z, Potor L, Nagy P, Sikura KÉ, Ditrói T, Jurányi EP, Galambos K, Szerafin T, Gergely P, Whiteman M, Torregrossa R, Ding Y, Beke L, Hendrik Z, Méhes G, Balla G, Balla J. Hydrogen sulfide as an anti-calcification stratagem in human aortic valve: Altered biogenesis and mitochondrial metabolism of H 2S lead to H 2S deficiency in calcific aortic valve disease. Redox Biol 2023; 60:102629. [PMID: 36780769 PMCID: PMC9947110 DOI: 10.1016/j.redox.2023.102629] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 02/06/2023] [Indexed: 02/10/2023] Open
Abstract
Hydrogen sulfide (H2S) was previously revealed to inhibit osteoblastic differentiation of valvular interstitial cells (VICs), a pathological feature in calcific aortic valve disease (CAVD). This study aimed to explore the metabolic control of H2S levels in human aortic valves. Lower levels of bioavailable H2S and higher levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected in aortic valves of CAVD patients compared to healthy individuals, accompanied by higher expression of cystathionine γ-lyase (CSE) and same expression of cystathionine β-synthase (CBS). Increased biogenesis of H2S by CSE was found in the aortic valves of CAVD patients which is supported by increased production of lanthionine. In accordance, healthy human aortic VICs mimic human pathology under calcifying conditions, as elevated CSE expression is associated with low levels of H2S. The expression of mitochondrial enzymes involved in H2S catabolism including sulfide quinone oxidoreductase (SQR), the key enzyme in mitochondrial H2S oxidation, persulfide dioxygenase (ETHE1), sulfite oxidase (SO) and thiosulfate sulfurtransferase (TST) were up-regulated in calcific aortic valve tissues, and a similar expression pattern was observed in response to high phosphate levels in VICs. AP39, a mitochondria-targeting H2S donor, rescued VICs from an osteoblastic phenotype switch and reduced the expression of IL-1β and TNF-α in VICs. Both pro-inflammatory cytokines aggravated calcification and osteoblastic differentiation of VICs derived from the calcific aortic valves. In contrast, IL-1β and TNF-α provided an early and transient inhibition of VICs calcification and osteoblastic differentiation in healthy cells and that effect was lost as H2S levels decreased. The benefit was mediated via CSE induction and H2S generation. We conclude that decreased levels of bioavailable H2S in human calcific aortic valves result from an increased H2S metabolism that facilitates the development of CAVD. CSE/H2S represent a pathway that reverses the action of calcifying stimuli.
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Affiliation(s)
- Zsolt Combi
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, University of Debrecen, 11003, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - László Potor
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, University of Debrecen, 11003, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - Péter Nagy
- Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary; Institute of Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary; Department of Anatomy and Histology, ELKH Laboratory of Redox Biology, University of Veterinary Medicine, Budapest, Hungary
| | - Katalin Éva Sikura
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, University of Debrecen, 11003, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - Tamás Ditrói
- Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
| | - Eszter Petra Jurányi
- Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary; Doctoral School of Molecular Medicine, Semmelweis University, Budapest, Hungary
| | - Klaudia Galambos
- Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary; Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
| | - Tamás Szerafin
- Department of Cardiac Surgery, Faculty of Medicine, University of Debrecen, Hungary
| | - Péter Gergely
- Institute of Forensic Medicine, Faculty of Medicine, University of Debrecen, Hungary
| | - Matthew Whiteman
- University of Exeter Medical School, St. Luke's Campus, Magdalen Road, Exeter, EX1 2LU, UK
| | - Roberta Torregrossa
- University of Exeter Medical School, St. Luke's Campus, Magdalen Road, Exeter, EX1 2LU, UK
| | - Yuchao Ding
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - Lívia Beke
- Institute of Pathology, Faculty of Medicine, University of Debrecen, Hungary
| | - Zoltán Hendrik
- Institute of Forensic Medicine, Faculty of Medicine, University of Debrecen, Hungary
| | - Gábor Méhes
- Institute of Pathology, Faculty of Medicine, University of Debrecen, Hungary
| | - György Balla
- ELKH-UD Vascular Pathophysiology Research Group, University of Debrecen, 11003, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary; Department of Pediatrics, Faculty of Medicine, University of Debrecen, Hungary
| | - József Balla
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, University of Debrecen, 11003, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary.
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Feng Y, Yu M, Wang C, Xia J, Huang L, Tang Y, Xiao Q, Pu L, Wang L, Li G, Li Y. BRG1 is involved in vascular calcification in chronic renal disease via autophagy of vascular smooth muscle cells. iScience 2023; 26:106485. [PMID: 37020968 PMCID: PMC10067948 DOI: 10.1016/j.isci.2023.106485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/03/2022] [Accepted: 03/20/2023] [Indexed: 04/04/2023] Open
Abstract
We aimed to investigate the mechanisms of Brahma related gene 1 (BRG1) in promoting vascular calcification in chronic kidney disease (CKD). The expression of BRG1 was examined in high phosphorus stimulated rat aortic smooth muscle cells (RASMCs) and calcified artery tissues from rat models and hemodialysis patients. Autophagosome formation was measured in high phosphorus stimulated RASMCs with and without BRG1 knock-down. We also detected the coexistence of BGR1 and exosomes, and measured the circulatory levels of BRG1 in the hemodialysis patients. BRG1 promoted the osteogenic transdifferentiation of RASMCs. Silencing BRG1 prevented autophagy from being induced by high phosphorus stimulation in RASMCs. Increased expression of BRG1 was observed in calcified blood vessels. Serum BRG1 level increased in the hemodialysis patients. BRG1 was involved in the development of high phosphorus induced osteogenic phenotype in vitro and in vivo, and its underlying mechanism might be facilitating autophagy.
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Mok Y, Wang F, Ballew SH, Menez S, Butler KR, Wagenknecht L, Sedaghat S, Lutsey PL, Coresh J, Blaha MJ, Matsushita K. Kidney function, bone-mineral metabolism markers, and calcification of coronary arteries, aorta, and cardiac valves in older adults. Atherosclerosis 2023; 368:35-43. [PMID: 36754659 PMCID: PMC9992265 DOI: 10.1016/j.atherosclerosis.2023.01.007] [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: 11/10/2022] [Accepted: 01/10/2023] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS The contribution of kidney dysfunction, especially at mild-to-moderate stages, and bone-mineral metabolism (BMM) markers to vascular calcification remains controversial or unclear. We comprehensively evaluated the association of kidney and BMM markers with coronary artery calcification (CAC) and extra-coronary calcification (ECC). METHODS In 1931 ARIC participants (age 73-95 years) without coronary heart disease at visit 7 (2018-19), we investigated the associations of estimated glomerular filtration rate (eGFR) (with creatinine, cystatin C, and both) and five serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) with high CAC and ECC (sex-race specific ≥75th vs. <75th percentile Agatston score) or any vs. zero CAC and ECC using multivariable logistic regression. For eGFR and BMM markers, we took their weighted cumulative averages from visit 1 (1987-89) to visit 5 (2011-13). RESULTS Lower eGFR, regardless of equations used, was not robustly associated with high CAC or ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed robust associations with high CAC (only when modeled continuously) and ECC, independently of kidney function (e.g., odds ratio 1.94 [95%CI 1.38-2.73] for high aortic valve calcification, in the highest vs. lowest quartile). Results were generally consistent when analyzing any CAC or ECC, although cystatin C-based eGFR <60 mL/min/1.73 m2 became significantly associated with mitral valve calcification (odds ratio 1.69 [1.10-2.60]). CONCLUSIONS Among kidney and BMM measures tested, only serum phosphorus demonstrated robust associations with both CAC and ECC, supporting a key role of phosphorus in the pathophysiology of vascular calcification.
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Affiliation(s)
- Yejin Mok
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Frances Wang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Shoshana H Ballew
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Steve Menez
- Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Kenneth R Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Lynne Wagenknecht
- Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Sanaz Sedaghat
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Pamela L Lutsey
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Michael J Blaha
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Kunihiro Matsushita
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
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Williams MJ, White SC, Joseph Z, Hruska KA. Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone-Vascular paradox, a therapeutic target, and a biomarker. Front Physiol 2023; 14:1120308. [PMID: 36776982 PMCID: PMC9909112 DOI: 10.3389/fphys.2023.1120308] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/17/2023] [Indexed: 01/27/2023] Open
Abstract
The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte specific protein. Its production by the vasculature in chronic kidney disease identifies the key role of vascular cell osteoblastic/osteocytic transdifferentiation in vascular calcification and renal osteodystrophy. Subsequent studies showing that inhibition of sclerostin activity by a monoclonal antibody improved bone remodeling as expected, but stimulated vascular calcification, demonstrate that vascular sclerostin functions to brake the Wnt stimulation of the calcification milieu. Thus, the target of therapy in the chronic kidney disease-mineral bone disorder is not inhibition of sclerostin function, which would intensify vascular calcification. Rather, decreasing sclerostin production by decreasing the vascular osteoblastic/osteocytic transdifferentiation is the goal. This might decrease vascular calcification, decrease vascular stiffness, decrease cardiac hypertrophy, decrease sclerostin production, reduce serum sclerostin and improve skeletal remodeling. Thus, the therapeutic target of the chronic kidney disease-mineral bone disorder may be vascular osteoblastic transdifferentiation, and sclerostin levels may be a useful biomarker for the diagnosis of the chronic kidney disease-mineral bone disorder and the progress of its therapy.
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Affiliation(s)
- Matthew J. Williams
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, Saint Louis, MO, United States
| | - Sarah C. White
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, Saint Louis, MO, United States
| | - Zachary Joseph
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, Saint Louis, MO, United States
| | - Keith A. Hruska
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, Saint Louis, MO, United States
- Departments of Medicine and Cell Biology, Washington University, Saint Louis, MO, United States
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Okabe H, Muraoka Y, Naka Y, Setoyama K, Inoue K, Miura T, Shimizu A, Anai R, Miyamoto T, Tsuda Y, Araki M, Sonoda S, Kataoka M. Malnutrition leads to the progression of coronary artery calcification in hemodialysis patients. PLoS One 2023; 18:e0280383. [PMID: 36638132 PMCID: PMC9838858 DOI: 10.1371/journal.pone.0280383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/26/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Malnutrition is considered a risk factor for cardiovascular disease in patients with chronic kidney disease. However, no in vivo studies have reported on using optical coherence tomography to evaluate the effect of nutritional status on coronary atherosclerosis in hemodialysis patients. We aimed to conduct a detailed analysis of the effect of nutritional status on the coronary arteries in hemodialysis patients. METHODS Among 64 hemodialysis patients who underwent percutaneous coronary interventions, 41 that underwent optical coherence tomography imaging were included in this study. And, among them, 24 patients that could also be evaluated using OCT also at the 6-month follow-up were included in this study. The patients were divided into two groups based on nutritional evaluation using the geriatric nutritional risk index. Culprit and non-culprit lesions were evaluated at baseline and after 6 months. RESULTS In the culprit lesions at baseline, the length of the lipid plaque was significantly smaller in the malnutrition group. In contrast, the thickness and length of the calcified plaque and the angle of the calcified nodule were significantly larger (each p < 0.01). In the non-culprit lesions, the 6-month change in the angle of the calcified plaque was significantly greater in the malnutrition group (p = 0.02). The significant factors that affected the change in the angle of calcification were "malnutrition at geriatric nutritional risk index" [odds ratio, 8.17; 95% confidence interval, 1.79 to 37.33; p < 0.01] and "serum phosphorus level" (odds ratio, 3.73; 95% confidence interval, 1.42 to 9.81; p < 0.01). CONCLUSIONS Appropriate management of nutritional status is crucial for suppressing the progression of coronary artery disease in hemodialysis patients.
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Affiliation(s)
- Hiroki Okabe
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yoshitaka Muraoka
- Division of cardiology, Japan Labor Health and Welfare Organization Kyushu Rosai Hospital, Kitakyushu, Japan
| | - Yutaro Naka
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Koshi Setoyama
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Konosuke Inoue
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Toshiya Miura
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Akiyoshi Shimizu
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Reo Anai
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Tetsu Miyamoto
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yuki Tsuda
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masaru Araki
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shinjo Sonoda
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Masaharu Kataoka
- The Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
- * E-mail:
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Ogami T, Zimmermann E, Zhu RC, Zhao Y, Ning Y, Kurlansky P, Stevens JS, Avgerinos DV, Patel VI, Takayama H. Proximal aortic repair in dialysis patients: A national database analysis. J Thorac Cardiovasc Surg 2023; 165:31-39.e5. [PMID: 33812684 DOI: 10.1016/j.jtcvs.2021.02.086] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 02/11/2021] [Accepted: 02/20/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Dialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort. METHODS Perioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database. RESULTS In patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome. CONCLUSIONS We described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.
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Affiliation(s)
- Takuya Ogami
- Department of Surgery, New York-Presbyterian/Queens, Flushing, NY
| | - Eric Zimmermann
- Department of Surgery, New York-Presbyterian/Queens, Flushing, NY
| | - Roger C Zhu
- Department of Surgery, New York-Presbyterian/Queens, Flushing, NY
| | - Yanling Zhao
- Division of Cardiothoracic and Vascular Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY
| | - Yuming Ning
- Division of Cardiothoracic and Vascular Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY
| | - Paul Kurlansky
- Division of Cardiothoracic and Vascular Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY
| | - Jacob S Stevens
- Department of Nephrology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY
| | - Dimitrios V Avgerinos
- Department of Cardiothoracic Surgery, New York-Presbyterian, Weill Cornell Medicine, New York, NY
| | - Virendra I Patel
- Department of Vascular Surgery, New York-Presbyterian, Columbia University Medical Center, New York, NY
| | - Hiroo Takayama
- Division of Cardiothoracic and Vascular Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY.
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Naser IA, Abutair AS, Zourob RJ, Qeshta RI, Tawil RL, Lafi AH, Bardwil RW, Tabasi FM. Nutritional Assessment of Adult Patients Undergoing Maintenance Hemodialysis in the Gaza Strip. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2023; 34:1-12. [PMID: 38092711 DOI: 10.4103/1319-2442.390997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023] Open
Abstract
Malnutrition is a common condition in patients undergoing hemodialysis (HD), and it is associated with increased morbidity and mortality. The main objective of the study was to evaluate the nutritional status of patients on maintenance HD. After applying eligibility criteria, 141 HD patients attending major governmental dialysis centers were randomly recruited in this cross-sectional study and assessed for nutritional status using the Patient-Generated Subjective Global Assessment (PG-SGA) tool. The PG-SGA categorizes patients as well-nourished, moderately malnourished, and severely malnourished. Different anthropometric measurements, laboratory investigations, blood pressure measurements, and 24-h dietary recall were collected from each patient. According to PG- SGA results, 78% of patients were moderately malnourished and 22% of patients were severely malnourished. The mean body mass index was 27.8 kg/m2, and 5.7% of patients were underweight. There were significant differences in the mid-upper arm muscle circumference (P = 0.020) between the PG-SGA groups. The total energy and protein intake were significantly (P <0.001) less than the recommended dietary intake by 1268.9 kcal and 41.4 g, respectively. The albumin level in 37.6% of patients was less than the normal level, and the results indicated that there were significant differences in serum iron (P = 0.022) between the moderately and severely malnourished patients. The results of this study indicated that all HD patients were suffering from different degrees of malnutrition and, unfortunately, most of their energy and nutrient intake was far less than the requirements, which might be the reason why they face nutritional and health risks.
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Affiliation(s)
- Ihab A Naser
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Al-Azhar University, Gaza, Palestine
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Burstad KM, Cladis DP, Vorland CJ, Wastney ME, Biruete A, Dominguez JM, O'Neill KD, Chen NX, Moe SM, Hill Gallant KM. Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats. JBMR Plus 2022; 6:e10698. [PMID: 36530183 PMCID: PMC9751657 DOI: 10.1002/jbm4.10698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/05/2022] [Accepted: 10/27/2022] [Indexed: 05/21/2024] Open
Abstract
Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Kendal M Burstad
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Dennis P Cladis
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Colby J Vorland
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Applied Health ScienceIndiana University School of Public Health‐BloomingtonBloomingtonINUSA
| | - Meryl E Wastney
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Annabel Biruete
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
- Department of Nutrition and DieteticsIndiana University‐Purdue University IndianapolisIndianapolisINUSA
| | - James M Dominguez
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Kalisha D O'Neill
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Neal X Chen
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Sharon M Moe
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
- Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA
- Department of MedicineRoudebush Veterans Affairs Medicine CenterIndianapolisINUSA
| | - Kathleen M Hill Gallant
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
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Kaur R, Singh R. Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications. Life Sci 2022; 311:121148. [DOI: 10.1016/j.lfs.2022.121148] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 10/22/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022]
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Nagasaka T, Amanai S, Ishibashi Y, Aihara K, Ohyama Y, Takama N, Koitabashi N, Ishii H. Long-term outcomes of intermediate coronary stenosis in patients undergoing hemodialysis after deferred revascularization based on fractional flow reserve. Catheter Cardiovasc Interv 2022; 100:971-978. [PMID: 36262079 DOI: 10.1002/ccd.30421] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/29/2022] [Accepted: 10/02/2022] [Indexed: 11/10/2022]
Abstract
OBJECTIVES This study aimed to assess the long-term outcomes of patients undergoing hemodialysis (HD) after deferred revascularization based on fractional flow reserve (FFR). BACKGROUND FFR is a practical technique for assessing the functional severity of intermediate coronary stenosis. Prior research has revealed a satisfactory outcome in patients after the deferral of percutaneous coronary intervention for coronary lesions based on FFR measurement. However, little research has been conducted focusing on patients undergoing HD. METHODS The retrospective study comprised 225 consecutive patients with FFR assessment and deferred revascularization between January 2016 and December 2019. Based on a deferral cutoff FFR value of >0.80, we assessed the differences in all-cause death, major adverse cardiac events (MACEs), and target vessel failure (TVF) between the HD (n = 69) and non-HD groups (n = 156) during a mean ± standard deviation routine follow-up of 32.2 ± 13.4 months. RESULTS Although the HD group had significantly higher rates of diabetes mellitus than the non-HD group (53.6% vs. 37.2%, p = 0.021), there were no significant differences in sex, left ventricular ejection fraction, or other risk factors between the groups, nor with respect to stenosis diameter or mean FFR. The HD group had a significantly higher incidence of TVF than the non-HD group (34.8% vs. 14.1%, p < 0.001), as well as a significantly higher risk of all-cause death and MACEs. CONCLUSIONS The study revealed that deferred revascularization in coronary lesions with an FFR value of >0.80 in patients undergoing HD was associated with poor outcomes. Therefore, it is important to carefully monitor patients with intermediate coronary stenosis undergoing HD.
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Affiliation(s)
- Takashi Nagasaka
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Shiro Amanai
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Yohei Ishibashi
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Kazufumi Aihara
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Yoshiaki Ohyama
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Noriaki Takama
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Norimichi Koitabashi
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
| | - Hideki Ishii
- Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan
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