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Seyahi N, Alagoz S, Atli Z, Ozcan SG, Tripepi G, Bakir A, Trabulus S, Pekmezci S, Zoccali C. Coronary artery calcification progression and long-term cardiovascular outcomes in renal transplant recipients: an analysis by the joint model. Clin Kidney J 2022; 15:101-108. [PMID: 35106150 PMCID: PMC8796795 DOI: 10.1093/ckj/sfab174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/23/2021] [Indexed: 01/07/2023] Open
Abstract
Background Compared with the general population, the risk of death is substantially higher in renal transplant recipients than in age- and sex-matched individuals in the general population. In the general population, coronary artery calcification (CAC) predicts all-cause and cardiovascular mortality. In this study we aimed to analyse these relationships in renal transplant recipients. Methods We examined 178 renal transplant patients in this prospective observational cohort study. We measured CAC with multidetector spiral computed tomography using the Agatston score at multiple time points. Overall, 411 scans were performed in 178 patients over an average 12.8 years follow-up. The clinical endpoint was a composite including all-cause death and non-fatal cardiovascular events. Data analysis was performed by the joint model. Results During a follow-up of 12.8 ± 2.4 years, coronary calcification progressed over time (P < 0.001) and the clinical endpoint occurred in 54 patients. In the analysis by the joint model, both the baseline CAC score and the CAC score progression were strongly associated with the incidence rate of the composite event [hazard ratio 1.261 (95% confidence interval 1.119–1.420), P = 0.0001]. Conclusions CAC at baseline and coronary calcification progression robustly predict the risk of death and cardiovascular events in renal transplant recipients. These findings support the hypothesis that the link between the calcifying arteriopathy of renal transplant patients and clinical end points in these patients is causal in nature.
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Affiliation(s)
- Nurhan Seyahi
- Department of Internal Medicine, Division of Nephrology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
| | - Selma Alagoz
- Department of Nephrology, Health Sciences University, Istanbul Training and Research Hospital, Istanbul, Turkey
| | - Zeynep Atli
- Department of Account and Tax Application, Sinop University, Sinop, Turkey
| | - Seyda Gul Ozcan
- Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Giovanni Tripepi
- Institute of Clinical Epidemiology, Clinical Epidemiology and Physiopathology of Renal Diseases, Hypertension of Reggio Calabria, Reggio Calabria, Italy
| | - Alev Bakir
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Halic University, Istanbul, Turkey
| | - Sinan Trabulus
- Department of Internal Medicine, Division of Nephrology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
| | - Salih Pekmezci
- Department of General Surgery, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Carmine Zoccali
- Associazione Ipertensione, Nefrologia, Trapianto Renale c/o Nephrology and Renal Transplantation Division Ospedali Riuniti, Reggio Calabria, Italy
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2
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Lees JS, Rankin AJ, Gillis KA, Zhu LY, Mangion K, Rutherford E, Roditi GH, Witham MD, Chantler D, Panarelli M, Jardine AG, Mark PB. The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients. Am J Transplant 2021; 21:3356-3368. [PMID: 33742520 DOI: 10.1111/ajt.16566] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/24/2021] [Accepted: 03/13/2021] [Indexed: 01/25/2023]
Abstract
Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3 mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.
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Affiliation(s)
- Jennifer S Lees
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Alastair J Rankin
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Keith A Gillis
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Luke Y Zhu
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Kenneth Mangion
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Elaine Rutherford
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Giles H Roditi
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Miles D Witham
- AGE Research Group, NIHR Newcastle Biomedical Research Centre, 3rd Floor Biomedical Research Building, Campus for Ageing and Vitality, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne, Glasgow, UK
| | - Donna Chantler
- Department of Clinical Biochemistry, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Maurizio Panarelli
- Department of Clinical Biochemistry, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Alan G Jardine
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Patrick B Mark
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.,Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
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Mukai H, Dai L, Chen Z, Lindholm B, Ripsweden J, Brismar TB, Heimbürger O, Barany P, Qureshi AR, Söderberg M, Bäck M, Stenvinkel P. Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease. Nephrol Dial Transplant 2020; 35:1202-1211. [PMID: 30534995 DOI: 10.1093/ndt/gfy352] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 09/28/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)]. METHODS In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients. RESULTS Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density. CONCLUSIONS In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification.
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Affiliation(s)
- Hideyuki Mukai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Zhimin Chen
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Magnus Söderberg
- Department of Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden
| | - Magnus Bäck
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
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4
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Incidence, risk factors and prognostic impact of acute kidney injury after coronary angiography and intervention in kidney transplant recipients: a single-center retrospective analysis. ADVANCES IN INTERVENTIONAL CARDIOLOGY 2020; 16:58-64. [PMID: 32368237 PMCID: PMC7189128 DOI: 10.5114/aic.2020.93913] [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: 06/18/2019] [Accepted: 10/03/2019] [Indexed: 11/25/2022] Open
Abstract
Introduction Kidney transplant recipients (KTR) represent a high-risk population for cardiovascular disease. Coronary artery disease (CAD) is the most common cause of morbidity and mortality in this population. In KTR, coronary angiography and intervention (CI) can be associated with the risk of acute kidney injury (AKI). Aim Data about the incidence and impact of AKI after CI in this population are rare. The aim of the present study is to describe the incidence and risk factors of AKI, periprocedural bleeding and the prognostic impact on 1-year mortality in KTR undergoing CI. Material and methods This retrospective single-center study includes all KTR undergoing CI at University Hospital Frankfurt between 2005 and 2015. Results A total of 135 CIs in KTR were analyzed. AKI occurred in 31 of 135 CIs (23%, AKI group). Patients of the AKI group were older; other baseline characteristics did not show significant differences. The amount of contrast dye used was higher in the AKI group (p = NS). Periprocedural bleeding defined by BARC criteria occurred more often in the AKI group (23% vs. 5%, p < 0.01) and persisted as a risk factor of AKI in multivariate analysis (odds ratio = 6.43, 95% CI: 1.78–23.20, p = 0.01). In-hospital mortality was 3% in the AKI group; no patient of the non-AKI group died during hospitalization (p = 0.2). One-year-survival was significantly higher in the non-AKI group (94% vs. 81%, p = 0.02). Conclusions AKI is an important prognostic determinant in KTR undergoing coronary angiography and percutaneous coronary intervention (PCI). Periprocedural bleeding events were associated with AKI. Well-known risk factors for AKI such as contrast agent and diabetes were of minor impact.
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5
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Lang J, Buettner S, Weiler H, Papadopoulos N, Geiger H, Hauser I, Vasa-Nicotera M, Zeiher A, Fichtlscherer S, Honold J. Comparison of interventional and surgical myocardial revascularization in kidney transplant recipients - A single-centre retrospective analysis. IJC HEART & VASCULATURE 2018; 21:96-102. [PMID: 30426068 PMCID: PMC6224329 DOI: 10.1016/j.ijcha.2018.10.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 10/19/2018] [Accepted: 10/24/2018] [Indexed: 01/22/2023]
Abstract
Background Kidney transplant recipients (KTR) reflect a high-risk population for coronary artery disease (CAD). CAD is the most common cause for morbidity and mortality in this population. However, only few data are available on the favourable revascularization strategy for these patients as they were often excluded from studies and not mentioned in guidelines. Methods This retrospective single-centre study includes patients with a history of kidney transplantation undergoing myocardial revascularization for multivessel or left main CAD by either percutaneous coronary intervention (PCI, n = 27 patients) or coronary artery bypass grafting (CABG, n = 24 patients) at University Hospital Frankfurt, Germany, between 2005 and 2015. Results In-hospital mortality was higher in the CABG group (20.8% vs. 14.8% PCI group; p = 0.45). In Kaplan-Meier analysis, one-year-survival showed better outcome in the PCI group (85.2% vs. 75%). After four years, outcome was comparable between both strategies (PCI 66.5% vs. CABG 70.8%; log-rank p = 0.94). Acute kidney injury (AKI), classified by Acute Kidney Injury Network, was observed more frequently after CABG (58.3% vs. 18.5%; p < 0.01). After one year, graft survival was 95.7% in the PCI group and 94.1% in the CABG group. Four year follow-up showed comparable graft survival in both groups (76.8% PCI and 77.0% CABG; p = 0.78). Conclusion In this retrospective single-centre study of KTR requiring myocardial revascularization, PCI seems to be superior to CABG with regard to in-hospital mortality, acute kidney injury and one-year-survival. To optimise treatment of these high-risk patients, larger-scaled studies are urgently warranted.
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Affiliation(s)
- Jeannine Lang
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Stefan Buettner
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Helge Weiler
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Nestoras Papadopoulos
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Helmut Geiger
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Ingeborg Hauser
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Mariuca Vasa-Nicotera
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Andreas Zeiher
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Stephan Fichtlscherer
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Joerg Honold
- Department of Internal Medicine III, Division of Cardiology and Nephrology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.,Division of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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6
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Chen Z, Sun J, Haarhaus M, Barany P, Wennberg L, Ripsweden J, Brismar TB, Lindholm B, Wernerson A, Söderberg M, Stenvinkel P, Qureshi AR. Bone mineral density of extremities is associated with coronary calcification and biopsy-verified vascular calcification in living-donor renal transplant recipients. J Bone Miner Metab 2017; 35:536-543. [PMID: 27913900 DOI: 10.1007/s00774-016-0788-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 09/12/2016] [Indexed: 12/21/2022]
Abstract
Chronic kidney disease (CKD) mineral and bone disorders (CKD-MBD) may lead to low bone mineral density (BMD) and vascular calcification (VC), but links to the latter are unclear. Here we investigated associations between BMD, coronary artery calcium (CAC) scores, and histological signs of VC in end-stage renal disease (ESRD) patients undergoing living-donor kidney transplantation (LD-Rtx). In 66 ESRD patients (median age 45 years, 68% males), BMD (by dual-energy X-ray absorptiometry, DXA), CAC score (by computed tomography, CT; n = 54), and degree of VC score (graded by histological examination of epigastric artery specimens collected at LD-Rtx; n = 55) were assessed at the time of LD-Rtx. Of the patients, 26% had osteopenia and 7% had osteoporosis. Of those undergoing artery biopsy, 16% had extensive VC, and of those undergoing CT 28% had high CAC score (>100 Agatston units). CAC scores correlated with BMD of legs and pelvis. BMDs of leg and pelvic sub-regions were significantly lower in patients with extensive VC. In multivariate regression analysis adjusted for age and gender, lower BMD of leg sub-region was associated with CAC score >100 AUs and extensive VC, and patients with extensive VC had significantly higher CAC score. Both high CAC and extensive VC were independently predicted by low BMD of legs. Low BMD has the potential to identify ESRD patients at risk of vascular calcification.
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Affiliation(s)
- Zhimin Chen
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
- Kidney Disease Center, 1st Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, China
| | - Jia Sun
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Mathias Haarhaus
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Peter Barany
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Lars Wennberg
- Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Jonaz Ripsweden
- Radiology, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | | | - Bengt Lindholm
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Annika Wernerson
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Magnus Söderberg
- Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden
| | - Peter Stenvinkel
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, M-99 Karolinska University Hospital, Huddinge, CLINTEC, SE-141 86, Stockholm, Sweden.
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7
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Gulcicek S, Zoccali C, Olgun DÇ, Tripepi G, Alagoz S, Yalın SF, Trabulus S, Altiparmak MR, Seyahi N. Long-Term Progression of Coronary Artery Calcification Is Independent of Classical Risk Factors, C-Reactive Protein, and Parathyroid Hormone in Renal Transplant Patients. Cardiorenal Med 2017; 7:284-294. [PMID: 29118767 DOI: 10.1159/000475999] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 04/10/2017] [Indexed: 12/28/2022] Open
Abstract
Aims Compared to the general population, mortality is significantly increased in renal transplant recipients. In the general population, coronary artery calcification (CAC) and its evolution over time are associated with cardiovascular and all-cause mortality, and the study of this biomarker could provide useful information for describing the long-term progression of coronary heart disease in renal transplant recipients. Methods We followed up a cohort of 113 renal transplant patients by performing three multi-detector computed tomography studies over 83.6 ± 6.8 months. Data analysis was performed by logistic regression analysis and by mixed linear modelling. Results Progression was observed in 34.5% of patients. Baseline CAC and time-to-transplantation were the sole variables that predicted CAC evolution over time. Neither classical nor nontraditional risk factors, biomarkers of renal function (GFR) and kidney damage (albuminuria) or biomarkers of bone mineral disorder (BMD), such as serum phosphorus, calcium, and PTH, were associated with the long-term progression of coronary calcification. Serum triglycerides predicted CAC progression only in logistic regression analysis, while in addition to baseline CAC, time to transplantation was the sole variable predicting CAC progression when the data were analyzed by mixed linear modelling. These data suggested that, in addition to the background calcification burden, other unmeasured factors play major roles in promoting the evolution of coronary calcification in the transplant population. Conclusion CAC progression continued over the long-term follow-up of renal transplant patients. This phenomenon was unaccounted for by classical and nontraditional risk factors, as well as by biomarkers of renal dysfunction and renal damage.
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Affiliation(s)
- Sibel Gulcicek
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Carmine Zoccali
- Nephrology and Renal Transplantation Division, Ospedali Riuniti, Reggio Calabria, Italy
| | - Deniz Çebi Olgun
- Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Giovanni Tripepi
- CNR-IFC, Institute of Clinical Epidemiology (IFC), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Reggio Calabria, Italy
| | - Selma Alagoz
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Serkan Feyyaz Yalın
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Sinan Trabulus
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Mehmet R Altiparmak
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Nurhan Seyahi
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
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8
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Sharaf El Din UAA, Salem MM, Abdulazim DO. Vascular calcification: When should we interfere in chronic kidney disease patients and how? World J Nephrol 2016; 5:398-417. [PMID: 27648404 PMCID: PMC5011247 DOI: 10.5527/wjn.v5.i5.398] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 04/20/2016] [Accepted: 06/27/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients.
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9
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Bavishi C, Argulian E, Chatterjee S, Rozanski A. CACS and the Frequency of Stress-Induced Myocardial Ischemia During MPI. JACC Cardiovasc Imaging 2016; 9:580-9. [DOI: 10.1016/j.jcmg.2015.11.023] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 11/12/2015] [Indexed: 11/24/2022]
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10
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Stróżecki P, Serafin Z, Adamowicz A, Flisiński M, Włodarczyk Z, Manitius J. Coronary artery calcification and large artery stiffness in renal transplant recipients. Adv Med Sci 2015; 60:240-5. [PMID: 25951498 DOI: 10.1016/j.advms.2015.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 03/31/2015] [Accepted: 04/10/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in renal transplant recipients (RTR). Carotid-femoral pulse wave velocity (PWV), a non-invasive measure of large artery stiffness, also predicts CV events in RTR. The study investigated the relationship between CAC and PWV in RTR and assessed the performance of PWV measurement in predicting CAC. PATIENTS/METHODS The study was performed as cross-sectional analysis in 104 RTR. CAC was determined as total calcium score (CS) and calcium mass (CM). Carotid-femoral PWV was also measured. Sensitivity, specificity and receiver operating characteristic (ROC) curve were used to assess the performance of PWV as diagnostic test for presence of CAC. RESULTS CAC was found in 69% of participants. PWV was higher in RTR with CAC than in RTR without CAC (10.2±2.2 vs. 8.6±15; p<0.001). In univariate analysis CS was significantly correlated with age, duration of hypertension, waist circumference, PWV, hemoglobin concentration, and serum glucose. In multiple linear regression analysis CS was independently associated with age only, but not with PWV. Sensitivity and specificity of PWV>7.6m/s as cut-off for detecting CAC>0 was 0.889 and 0.406, respectively. Sensitivity and specificity of PWV>10.2m/s as cut-off for detecting severe CAC (CS>400) was 0.319 and 0.969, respectively. CONCLUSIONS The study confirmed high prevalence of coronary artery calcification in renal transplant recipients. The study does not support the hypothesis that aortic stiffness is independently associated with coronary artery calcification in RTR. PWV measurement may be useful in excluding severe CAC in RTR.
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Lee SH, Huh KH, Kim BK, Choi BW, Kim YJ, Kim YS, Kim BS. Clinical significance of multidetector coronary computed tomography angiography to evaluate the prevalence and severity of coronary artery disease in asymptomatic kidney transplantation recipients. Transplant Proc 2015; 47:675-8. [PMID: 25891709 DOI: 10.1016/j.transproceed.2014.12.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Accepted: 12/31/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND Coronary artery disease (CAD) is one of the leading causes of mortality in kidney transplantation (KT) recipients. Noninvasive coronary angiography with the use of multidetector computerized tomography (MDCT) is feasible with high sensitivity and negative predictive value to evaluate CAD. However, few studies have been conducted to elucidate the applicability of MDCT in KT. This study was designed to evaluate the prevalence and severity of CAD with the use of MDCT angiography in asymptomatic KT recipients. METHODS From September 2011 to November 2013, MDCT angiography was performed on 90 renal transplant recipients who had no pre-transplantation CAD history and stabilized post-transplantation renal function for 6-18 months. According to the MDCT results, we divided our study population into 2 groups: The no-CAD group (n = 36; 40.0%) and the CAD group (n = 54; 60.0%). Severity of CAD was categorized as follows: mild CAD, 1 vessel obstructive, 2 vessels obstructive (or in the proximal left anterior descending), and 3 vessels obstructive (or left main). RESULTS Among the risk factors, pre-transplantation diabetes mellitus and lower levels of high-density lipoprotein, higher parathyroid hormone levels, higher coronary artery calcification scores, and rejection episodes were independent factors for CAD. Thirty-two (59.3%) of the CAD group had mild obstructive lesions and 22 (40.7%) had obstructive lesions in >1 vessel according to MDCT angiography. CONCLUSIONS MDCT angiography is a useful and noninvasive method for detecting CAD even in asymptomatic KT recipients.
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Affiliation(s)
- S H Lee
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - K H Huh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea; Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - B K Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - B W Choi
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Y J Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Y S Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea; Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - B S Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
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Association of serum fetuin-A and fetuin-A gene polymorphism in relation to mineral and bone disorders in patients with chronic kidney disease. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2013. [DOI: 10.1016/j.ejmhg.2013.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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13
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Stompór T, Pawłowska A, Kozielec Z, Wasilewski G, Stefanowicz E. Advanced abdominal arterial calcification sparing kidney allograft--case report. Ren Fail 2013; 35:1031-4. [PMID: 23826826 DOI: 10.3109/0886022x.2013.810156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Excess and progressing arterial calcification is a frequent finding in patients with chronic kidney disease and in diabetics. Vascular calcification present in patients on dialysis, usually continues to progress (although possibly with slower rate) in patients after kidney transplantation. These observations are limited mostly to aorta and coronary arteries; virtually no data exist on progression in vascular calcification within the vasculature of transplanted kidney. The case report presents the patient with diabetes and non-functioning renal transplant back on dialysis with extremely severe intra-abdominal artery calcification, sparing renal artery of transplanted kidney. Calcification did not develop within transplanted kidney despite 10 years of exposition to diabetic environment and a few years of chronic kidney disease after transplantation, including CKD-T stage 5 for at least one year after re-starting of dialysis. To the best of our knowledge, this is the second report ever describing sparing of kidney graft from calcification despite disseminated calcification in other vascular beds. It is tempting to speculate that some "intrinsic" factors exist within the transplanted kidney that protects it from calcification despite exposure to procalcifying milieu of diabetes and uremia.
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Affiliation(s)
- Tomasz Stompór
- Department of Nephrology, Hypertension and Internal Medicine, Medical Faculty, University of Warmia and Mazury, Olsztyn, Poland.
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Yazbek D, de Carvalho A, Barros C, Marcassi A, Pestana J, Fachini F, Cassiolato J, Canziani M. Cardiovascular Disease in Early Kidney Transplantation: Comparison Between Living and Deceased Donor Recipients. Transplant Proc 2012. [DOI: 10.1016/j.transproceed.2012.03.061] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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15
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Gudmundsson EF, Gudnason V, Sigurdsson S, Launer LJ, Harris TB, Aspelund T. Coronary artery calcium distributions in older persons in the AGES-Reykjavik study. Eur J Epidemiol 2012; 27:673-87. [PMID: 22990371 DOI: 10.1007/s10654-012-9730-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 08/28/2012] [Indexed: 01/12/2023]
Abstract
Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an independent risk factor for cardiac events. Here, we describe CAC-distributions in an unselected aged population and compare modelling methods to characterize CAC-distribution. CAC is difficult to model because it has a skewed and zero inflated distribution with over-dispersion. Data are from the AGES-Reykjavik sample, a large population based study [2002-2006] in Iceland of 5,764 persons aged 66-96 years. Linear regressions using logarithmic- and Box-Cox transformations on CAC+1, quantile regression and a Zero-Inflated Negative Binomial model (ZINB) were applied. Methods were compared visually and with the PRESS-statistic, R(2) and number of detected associations with concurrently measured variables. There were pronounced differences in CAC according to sex, age, history of coronary events and presence of plaque in the carotid artery. Associations with conventional coronary artery disease (CAD) risk factors varied between the sexes. The ZINB model provided the best results with respect to the PRESS-statistic, R(2), and predicted proportion of zero scores. The ZINB model detected similar numbers of associations as the linear regression on ln(CAC+1) and usually with the same risk factors.
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Fibroblast Growth Factor and Mineral Metabolism Parameters among Prevalent Kidney Transplant Patients. Int J Nephrol 2012; 2012:490623. [PMID: 22811905 PMCID: PMC3395143 DOI: 10.1155/2012/490623] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Accepted: 04/23/2012] [Indexed: 12/11/2022] Open
Abstract
Background. Chronic kidney disease (CKD) related mineral bone disorders persist after kidney transplantation, but little is known about the relationship between fibroblast growth factor-23 (FGF-23) and mineral metabolism in prevalent post-transplant patients. Objectives. To examine mineral metabolism parameters and their relationship to FGF-23 and parathyroid hormone (PTH) in prevalent kidney transplant patients. Methods. Cross-sectional study of 106 kidney transplant patients enrolled November 2005–October 2009 at Tufts Medical Center (TMC), Boston. Results. The prevalence of hypophosphatemia was 34%, hypercalcemia 3%, and elevated PTH levels 66%, at a median (25th–75th percentile) duration of 12.8 (7.5–30.9) months post-transplant. Males had significantly higher levels of PTH (P = 0.04) and lower levels of serum phosphate
(P = 0.002). Serum PTH levels did not relate to eGFR, corrected calcium levels or serum phosphate. FGF-23 levels were above the reference limits in 7% of patients; higher levels were associated with higher serum phosphate and PTH levels after adjustment for transplant kidney function. Conclusion. FGF-23 is an important driver of mineral metabolism in prevalent transplant patients. Its modulatory role in mineral metabolism homeostasis may be heightened as feedback suppression of PTH is disturbed. Its role in long term cardiovascular and graft outcomes needs further study.
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Simic-Ogrizovic S, Bogavac-Stanojevic N, Vuckovic M, Dopsaj V, Giga V, Kravljaca M, Stosovic M, Lezaic V. Risk Factors Associated with Coronary Artery Calcification Should Be Examined before Kidney Transplantation. TOHOKU J EXP MED 2012; 226:137-44. [DOI: 10.1620/tjem.226.137] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
| | | | | | | | - Voja Giga
- Cardiology Clinic, Clinical Centre of Serbia
| | | | | | - Visnja Lezaic
- Nephrology Clinic, Clinical Centre of Serbia
- School of Medicine, Belgrade University
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Seyahi N, Cebi D, Altiparmak MR, Akman C, Ataman R, Pekmezci S, Serdengecti K. Progression of coronary artery calcification in renal transplant recipients. Nephrol Dial Transplant 2011; 27:2101-7. [PMID: 21965591 DOI: 10.1093/ndt/gfr558] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Cardiovascular disease is the leading cause of mortality among renal transplant recipients. In the general population, coronary artery calcification (CAC) and progression of CAC are predictors of future cardiac risk. We conducted a study to determine the progression of CAC in renal transplant recipients; we also examined the factors associated with progression and the impact of the analytic methods used to determine CAC progression. METHODS We used multi-detector computed tomography to examine CAC in 150 prevalent renal transplant recipients, who did not have a documented cardiovascular disease. A baseline and a follow-up scan were performed and changes in CAC scores were evaluated in each patient individually, to calculate the incidence of CAC progression. Multivariate logistic regression analysis was used to evaluate the determinants of CAC progression. RESULTS Baseline CAC prevalence was 35.3% and the mean CAC score was 60.0 ± 174.8. At follow-up scan that was performed after an average of 2.8 ± 0.4 years, CAC prevalence increased to 64.6% and the mean CAC score to 94.9 ± 245.7. Progression of individual CAC score was found between 28.0 and 38.0%, depending on the method used to define progression. In patients with baseline CAC, median annualized rate of CAC progression was 11.1. Baseline CAC, high triglyceride and bisphosphonate use were the independent determinants of CAC progression. CONCLUSIONS Renal transplantation does not stop or reverse CAC. Progression of CAC is the usual evolution pattern of CAC in renal transplant recipients. Beside baseline CAC, high triglyceride level and bisphosphonate use were associated with progression of CAC.
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Affiliation(s)
- Nurhan Seyahi
- Department of Internal Medicine, Division of Nephrology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
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