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Wang X, Cao J, Wang Y, Li M, Hou S, Zhao Z, Yang M, Ju P, Jiang Y, Xiao J, Tang R, Liu H, Liu B, Zhang X, Wang B. Association of Muscle Radiodensity and Muscle Mass With Thoracic Aortic Calcification Progression in Dialysis Patients. J Cachexia Sarcopenia Muscle 2025; 16:e13813. [PMID: 40241470 PMCID: PMC12003956 DOI: 10.1002/jcsm.13813] [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: 09/11/2024] [Revised: 03/12/2025] [Accepted: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Recent findings have spotlighted sarcopenia as a critical factor exacerbating cardiovascular risk in dialysis patients. However, no studies have investigated the relationship of muscle characteristics with thoracic aortic calcification (TAC). We explored whether skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) are associated with TAC in dialysis patients. METHODS In this study, 2517 dialysis patients (between January 2020 and June 2023) from four centres with chest computed tomography (CT) scans were analysed cross-sectionally. A cohort of 544 initial-dialysis patients (between January 2014 and December 2020) was followed for TAC progression. Chest CT images were used to assess SMD and SMI at the L1 level, as well as to measure the scores of TAC, including ascending TAC (ATAC), aortic arch calcification (AoAC) and descending TAC (DTAC). Multivariable linear regression models were employed to assess the effects of SMD and SMI on TAC and its progression. Restricted cubic spline was used to assess the potential non-linear relationships of SMD and SMI with TAC progression. RESULTS The mean (SD) age for the cross-sectional study was 54.8 (14.0) years, with males accounting for 58.2%. Over a mean (SD) follow-up duration of 3.45 (1.82) years, 85.7% showed TAC progression. Comparing the highest quartile of SMD to the lowest quartile, a significant inverse association was observed with TAC (β, -1.08 [-1.42 to -0.75]; p < 0.001); similar trends were noted for SMI (β, -0.42 [-0.74 to -0.10]; p = 0.011). SMD and SMI as continuous variables were also both significantly negatively correlated with TAC. In the longitudinal study, multivariable linear regression models revealed that an increase of 1 SD in SMD resulted in a decrease of 0.10 SD (95% CI, -0.17 to -0.02; p = 0.011) in TAC progression, and an increase of 1 SD in SMI resulted in a decrease of 0.12 SD (95% CI, -0.20 to -0.04; p = 0.003) in TAC progression. Restricted cubic spline models excluded non-linear trends for the relationships of SMD and SMI with TAC progression. The associations of SMD and SMI with DTAC were consistent with those observed for TAC, but neither showed a significant association with ATAC. CONCLUSIONS Higher SMD and higher SMI were significantly associated with lower TAC and its progression in dialysis patients. Improving SMD and SMI could be a new approach for reducing TAC.
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Affiliation(s)
- Xiao‐xu Wang
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
- School of MedicineSoutheast UniversityNanjingChina
| | - Jing‐yuan Cao
- Department of Nephrology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical MedicineNanjing Medical UniversityTaizhouChina
| | - Yao Wang
- Department of Nephrology, The Affiliated Hospital of Yangzhou UniversityYangzhou UniversityYangzhouChina
| | - Min Li
- Department of Nephrology, The Third Affiliated Hospital of Soochow UniversitySoochow UniversityChangzhouChina
| | - Shi‐mei Hou
- Department of Nephrology, The Third Affiliated Hospital of Soochow UniversitySoochow UniversityChangzhouChina
| | - Zhen Zhao
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
| | - Min Yang
- Department of Nephrology, The Third Affiliated Hospital of Soochow UniversitySoochow UniversityChangzhouChina
| | - Ping‐ping Ju
- Department of Nephrology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical MedicineNanjing Medical UniversityTaizhouChina
| | - Yu‐jia Jiang
- Department of Nephrology, The Affiliated Hospital of Yangzhou UniversityYangzhou UniversityYangzhouChina
| | - Jing‐jie Xiao
- Covenant Health Palliative InstituteEdmontonAlbertaCanada
| | - Ri‐ring Tang
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
| | - Hong Liu
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
| | - Bi‐cheng Liu
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
| | - Xiao‐liang Zhang
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
| | - Bin Wang
- Department of Nephrology, Zhongda HospitalSoutheast University School of MedicineNanjingChina
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Rodrigues FG, Bruins MSM, Vliegenthart R, Kremer D, Sotomayor CG, Nolte IM, Douwe J Mulder U, Navis GJ, Heilberg IP, Pol RA, Bakker SJL, de Borst MH, Te Velde-Keyzer CA. Phase angle and donor type are determinants of coronary artery calcification in stable kidney transplant recipients at twelve months after transplantation. Nutr Metab Cardiovasc Dis 2024; 34:1912-1921. [PMID: 38740537 DOI: 10.1016/j.numecd.2024.04.008] [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: 10/31/2023] [Revised: 04/03/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND AND AIM Coronary artery calcification (CAC) partially explains the excess cardiovascular morbidity and mortality after kidney transplantation. This study aimed to investigate determinants of CAC in stable kidney transplant recipients at 12 months post-transplantation. METHODS AND RESULTS CAC-score was quantified by the Agatston method using non-contrast enhanced computed tomography, and age- and sex-standardized CAC-percentiles were calculated. Univariable and multivariable multinomial logistic regression was performed to study potential determinants of CAC. The independent determinants were included in multivariable multinomial logistic regression adjusting for potential confounders. 203 KTRs (age 54.0 ± 14.7 years, 61.1% male) were included. Participants were categorized into four groups according to CAC percentiles (p = 0 [CAC-score = 0], n = 68; p ≥ 1%-p ≤ 50% [CAC score = 29.0 (4.0-166.0)], n = 31; p > 50 ≤ 75% [CAC score = 101.0 (23.8-348.3)], n = 26; and p>75% [CAC score = 581.0 (148.0-1652)], n = 83). Upon multivariable multinomial logistic regression, patients with a narrower phase angle and patients who had received a graft from a deceased donor had a higher risk of being in the >75th CAC-percentile. CONCLUSIONS This study identifies not only metabolic and transplant-related factors, but also phase angle, a composite marker of cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. This study offers new perspectives for future research into the value of bioelectrical impedance analysis in relation to vascular calcification in kidney transplant recipients.
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Affiliation(s)
- Fernanda G Rodrigues
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Nutrition Post Graduation Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
| | - Megan S M Bruins
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Rozemarijn Vliegenthart
- Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Daan Kremer
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Camilo G Sotomayor
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ilja M Nolte
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Udo Douwe J Mulder
- Department of Internal Medicine, Division Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Gerjan J Navis
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ita Pfeferman Heilberg
- Nutrition Post Graduation Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Robert A Pol
- Department of Vascular and Transplant Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Martin H de Borst
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Charlotte A Te Velde-Keyzer
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Mencke R, Al Ali L, de Koning MSLY, Pasch A, Minnion M, Feelisch M, van Veldhuisen DJ, van der Horst ICC, Gansevoort RT, Bakker SJL, de Borst MH, van Goor H, van der Harst P, Lipsic E, Hillebrands JL. Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role Independent of Classical Cardiovascular Risk Factors. Arterioscler Thromb Vasc Biol 2024; 44:1884-1894. [PMID: 38899469 DOI: 10.1161/atvbaha.124.320974] [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: 03/20/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome. METHODS T50 was measured by nephelometry in 347 patients from the GIPS-III trial (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction: a Randomized Controlled Trial) and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. RESULTS Patients with ST-segment-elevated myocardial infarction had a significantly lower T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL (P=0.03) and had a significant interaction term for T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. CONCLUSIONS Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.
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Affiliation(s)
- Rik Mencke
- Department of Pathology and Medical Biology, Division of Pathology (R.M., H.v.G., J.L.H.), University Medical Center Groningen, the Netherlands
| | - Lawien Al Ali
- Department of Cardiology (L.A.A., M.-S.L.Y.d.K., D.J.v.V., P.v.d.H., E.L.), University Medical Center Groningen, the Netherlands
| | - Marie-Sophie L Y de Koning
- Department of Cardiology (L.A.A., M.-S.L.Y.d.K., D.J.v.V., P.v.d.H., E.L.), University Medical Center Groningen, the Netherlands
| | - Andreas Pasch
- Calciscon AG, Biel, Switzerland (A.P.)
- Institute of Physiology and Pathophysiology, Johannes Kepler University Linz, Austria (A.P.)
| | - Magdalena Minnion
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom (M.M., M.F.)
| | - Martin Feelisch
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom (M.M., M.F.)
| | - Dirk J van Veldhuisen
- Department of Cardiology (L.A.A., M.-S.L.Y.d.K., D.J.v.V., P.v.d.H., E.L.), University Medical Center Groningen, the Netherlands
| | | | - Ron T Gansevoort
- Department of Internal Medicine, Division of Nephrology (R.T.G., S.J.L.B., M.H.d.B.), University Medical Center Groningen, the Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology (R.T.G., S.J.L.B., M.H.d.B.), University Medical Center Groningen, the Netherlands
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology (R.T.G., S.J.L.B., M.H.d.B.), University Medical Center Groningen, the Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, Division of Pathology (R.M., H.v.G., J.L.H.), University Medical Center Groningen, the Netherlands
| | - Pim van der Harst
- Department of Cardiology (L.A.A., M.-S.L.Y.d.K., D.J.v.V., P.v.d.H., E.L.), University Medical Center Groningen, the Netherlands
- Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, the Netherlands (P.v.d.H.)
| | - Erik Lipsic
- Department of Cardiology (L.A.A., M.-S.L.Y.d.K., D.J.v.V., P.v.d.H., E.L.), University Medical Center Groningen, the Netherlands
| | - Jan-Luuk Hillebrands
- Department of Pathology and Medical Biology, Division of Pathology (R.M., H.v.G., J.L.H.), University Medical Center Groningen, the Netherlands
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Neytchev O, Erlandsson H, Witasp A, Nordfors L, Qureshi AR, Iseri K, Morohoshi H, Selman C, Ebert T, Kublickiene K, Stenvinkel P, Shiels PG. Epigenetic clocks indicate that kidney transplantation and not dialysis mitigate the effects of renal ageing. J Intern Med 2024; 295:79-90. [PMID: 37827529 DOI: 10.1111/joim.13724] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is an age-related disease that displays multiple features of accelerated ageing. It is currently unclear whether the two treatment options for end-stage kidney disease (dialysis and kidney transplantation [KT]) ameliorate the accelerated uremic ageing process. METHODS Data on clinical variables and blood DNA methylation (DNAm) from CKD stage G3-G5 patients were used to estimate biological age based on blood biomarkers (phenotypic age [PA], n = 333), skin autofluorescence (SAF age, n = 199) and DNAm (Horvath, Hannum and PhenoAge clocks, n = 47). In the DNAm cohort, we also measured the change in biological age 1 year after the KT or initiation of dialysis. Healthy subjects recruited from the general population were included as controls. RESULTS All three DNAm clocks indicated an increased biological age in CKD G5. However, PA and SAF age tended to produce implausibly large estimates of biological age in CKD G5. By contrast, DNAm age was 4.9 years (p = 0.005) higher in the transplantation group and 5.9 years (p = 0.001) higher in the dialysis group compared to controls. This age acceleration was significantly reduced 1 year after KT, but not after 1 year of dialysis. CONCLUSIONS Kidney failure patients displayed an increased biological age as estimated by DNAm clocks compared to population-based controls. Our results suggest that KT, but not dialysis, partially reduces the age acceleration.
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Affiliation(s)
- Ognian Neytchev
- College of Medical, Veterinary & Life Sciences, School of Molecular Biosciences, University of Glasgow, Glasgow, UK
| | - Helen Erlandsson
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Anna Witasp
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Louise Nordfors
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ken Iseri
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Hokuto Morohoshi
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Colin Selman
- College of Medical, Veterinary & Life Sciences, Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK
| | - Thomas Ebert
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Karolina Kublickiene
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Paul G Shiels
- College of Medical, Veterinary & Life Sciences, School of Molecular Biosciences, University of Glasgow, Glasgow, UK
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Sun L, Huang Z, Fei S, Ni B, Wang Z, Chen H, Tao J, Han Z, Ju X, Gu M, Tan R. Vascular calcification progression and its association with mineral and bone disorder in kidney transplant recipients. Ren Fail 2023; 45:2276382. [PMID: 37936391 PMCID: PMC10653689 DOI: 10.1080/0886022x.2023.2276382] [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: 07/07/2023] [Accepted: 10/23/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND The assessment and prevention of vascular calcification (VC) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate VC change one year after kidney transplantation (KT) and identify their influencing factors. METHODS 95 KTRs (68 males; ages 40.2 ± 10.8 years) were followed one year after KT. Changes in bone mineral density (BMD) and bone metabolism biomarkers were assessed. Coronary artery calcification (CAC) and thoracic aortic calcification (TAC) were measured using 192-slice third-generation dual-source CT. The relationship between bone metabolism indicators and VC and the factors influencing VC were analyzed. RESULTS Postoperative estimated glomerular filtration rate was 79.96 ± 24.18 mL/min*1.73 m2. One year after KT, serum phosphorus, intact parathyroid hormone (iPTH), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide, and BMD decreased, 25-hydroxyvitamin D remained low, and VC increased. Post-CAC and TAC were negatively correlated with pre-femoral neck BMD, and TAC was positively correlated with post-calcium. CAC and TAC change were positively correlated with post-calcium and 25-hydroxyvitamin D. Increased CAC was positively associated with hemodialysis and pre-femoral neck osteopenia. CAC change was positively associated with prediabetes, post-calcium, and pre-CAC and negatively associated with preoperative and postoperative femoral neck BMD, and NTx change. Increased TAC was positively associated with age, prediabetes, preoperative parathyroid hyperplasia/nodule, post-calcium, and post-femoral neck osteopenia. TAC change was positively associated with age, diabetes, pre-triglyceride, pre-TAC, dialysis time, post-calcium and post-iPTH, and negatively associated with post-femoral neck BMD. CONCLUSIONS Mineral and bone disorders persisted, and VC progressed after KT, showing a close relationship.
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Affiliation(s)
- Li Sun
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhengkai Huang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shuang Fei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bin Ni
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zijie Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Tao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhijian Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobing Ju
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruoyun Tan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Shahraki MN, Jouabadi SM, Bos D, Stricker BH, Ahmadizar F. Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials. Curr Atheroscler Rep 2023; 25:769-784. [PMID: 37796384 PMCID: PMC10618336 DOI: 10.1007/s11883-023-01151-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2023] [Indexed: 10/06/2023]
Abstract
PURPOSE OF REVIEW This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach.
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Affiliation(s)
- Mitra Nekouei Shahraki
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Soroush Mohammadi Jouabadi
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
- Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Daniel Bos
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
- Department of Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Bruno H Stricker
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Fariba Ahmadizar
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
- Department of Data Science and Biostatistics, Julius Global Health, University Medical Center Utrecht, Utrecht, The Netherlands.
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Koh HB, Ryu JH, Kim SS, Kim MG, Park JB, Kim CD, Kang KP, Ro H, Han SY, Huh KH, Yang J. Association between sclerostin levels and vascular outcomes in kidney transplantation patients. J Nephrol 2023; 36:2091-2109. [PMID: 37751127 DOI: 10.1007/s40620-023-01732-7] [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: 05/06/2023] [Accepted: 07/03/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND The impact of circulating sclerostin levels on vascular calcification has shown conflicting results depending on the target population and vascular anatomy. This study investigated the associations of sclerostin levels with vascular outcomes in kidney transplant patients. METHODS In a prospective observational study of the Korean Cohort Study for Outcome in Patients with Kidney Transplantation, 591 patients with serum sclerostin level data prior to transplantation were analyzed. The main predictor was the pre-transplant sclerostin level. Vascular outcomes were the abdominal aortic calcification score and brachial-ankle pulse wave velocity measured at pre-transplant screening and three and five years after kidney transplantation. RESULTS In linear regression analysis, sclerostin level positively correlated with changes in abdominal aortic calcification score between baseline and five years after kidney transplantation (coefficient of 0.73 [95% CI, 0.11-1.35] and 0.74 [95% CI, 0.06-1.42] for second and third tertiles, respectively, vs the first tertile). In a longitudinal analysis over five years, using generalized estimating equations, the coefficient of the interaction (sclerostin × time) was significant with a positive value, indicating that higher sclerostin levels were associated with faster increase in post-transplant abdominal aortic calcification score. Linear regression analysis revealed a positive association between pre-transplant sclerostin levels and changes in brachial-ankle pulse wave velocity (coefficient of 126.7 [95% CI, 35.6-217.8], third vs first tertile). Moreover, a significant interaction was identified between sclerostin levels and brachial-ankle pulse wave velocity at five years. CONCLUSIONS Elevated pre-transplant sclerostin levels are associated with the progression of post-transplant aortic calcifications and arterial stiffness.
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Affiliation(s)
- Hee Byung Koh
- Department of Internal Medicine, Catholic Kwandong University International Saint Mary's Hospital, Incheon, Republic of Korea
| | - Jung Hwa Ryu
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea
| | - Seung-Seob Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myung-Gyu Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jae Berm Park
- Department of Surgery, Seoul Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Chan Duk Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Kyung Pyo Kang
- Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Han Ro
- Department of Internal Medicine, Gil Hospital, Gachon University, Incheon, Republic of Korea
| | - Seung-Yeup Han
- Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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Hammer N, Legouis D, Pasch A, Huber A, Al-Qusairi L, Martin PY, de Seigneux S, Berchtold L. Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients. J Clin Med 2023; 12:3965. [PMID: 37373661 DOI: 10.3390/jcm12123965] [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: 05/21/2023] [Revised: 06/04/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. METHODS We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. RESULTS During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. CONCLUSION T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.
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Affiliation(s)
| | - David Legouis
- Division of Intensive Care, University Hospital of Geneva, 1205 Geneva, Switzerland
| | - Andreas Pasch
- Calciscon AG, 2503 Biel, Switzerland
- Department of Physiology and Pathophysiology, Johannes Kepler University, 4040 Linz, Austria
| | - Aurélie Huber
- Service of Internal Medicine, Hospital La Chaux-de-Fonds, 2000 Neuchatel, Switzerland
| | - Lama Al-Qusairi
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA
| | - Pierre-Yves Martin
- Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, 1205 Geneva, Switzerland
| | - Sophie de Seigneux
- Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, 1205 Geneva, Switzerland
| | - Lena Berchtold
- Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, 1205 Geneva, Switzerland
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9
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Hobson S, Arefin S, Rahman A, Hernandez L, Ebert T, de Loor H, Evenepoel P, Stenvinkel P, Kublickiene K. Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation. Int J Mol Sci 2023; 24:ijms24043640. [PMID: 36835051 PMCID: PMC9960432 DOI: 10.3390/ijms24043640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 02/02/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.
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Affiliation(s)
- Sam Hobson
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
| | - Samsul Arefin
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
| | - Awahan Rahman
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
| | - Leah Hernandez
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
| | - Thomas Ebert
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
- Medical Department III—Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, D-04103 Leipzig, Germany
| | - Henriette de Loor
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium
| | - Pieter Evenepoel
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, BE-3000 Leuven, Belgium
| | - Peter Stenvinkel
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
| | - Karolina Kublickiene
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden
- Correspondence:
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10
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Pan W, Jie W, Huang H. Vascular calcification: Molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2023; 4:e200. [PMID: 36620697 PMCID: PMC9811665 DOI: 10.1002/mco2.200] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 01/05/2023] Open
Abstract
Vascular calcification (VC) is recognized as a pathological vascular disorder associated with various diseases, such as atherosclerosis, hypertension, aortic valve stenosis, coronary artery disease, diabetes mellitus, as well as chronic kidney disease. Therefore, it is a life-threatening state for human health. There were several studies targeting mechanisms of VC that revealed the importance of vascular smooth muscle cells transdifferentiating, phosphorous and calcium milieu, as well as matrix vesicles on the progress of VC. However, the underlying molecular mechanisms of VC need to be elucidated. Though there is no acknowledged effective therapeutic strategy to reverse or cure VC clinically, recent evidence has proved that VC is not a passive irreversible comorbidity but an active process regulated by many factors. Some available approaches targeting the underlying molecular mechanism provide promising prospects for the therapy of VC. This review aims to summarize the novel findings on molecular mechanisms and therapeutic interventions of VC, including the role of inflammatory responses, endoplasmic reticulum stress, mitochondrial dysfunction, iron homeostasis, metabolic imbalance, and some related signaling pathways on VC progression. We also conclude some recent studies on controversial interventions in the clinical practice of VC, such as calcium channel blockers, renin-angiotensin system inhibitions, statins, bisphosphonates, denosumab, vitamins, and ion conditioning agents.
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Affiliation(s)
- Wei Pan
- Department of Cardiology, the Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenGuangdongChina
- Joint Laboratory of Guangdong‐Hong Kong‐Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic DiseaseSun Yat‐sen UniversityShenzhenGuangdongChina
| | - Wei Jie
- Department of Cardiology, the Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenGuangdongChina
- Joint Laboratory of Guangdong‐Hong Kong‐Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic DiseaseSun Yat‐sen UniversityShenzhenGuangdongChina
| | - Hui Huang
- Department of Cardiology, the Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenGuangdongChina
- Joint Laboratory of Guangdong‐Hong Kong‐Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic DiseaseSun Yat‐sen UniversityShenzhenGuangdongChina
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11
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Rijkse E, Roodnat JI, Baart SJ, Bijdevaate DC, Dijkshoorn ML, Kimenai HJAN, van de Wetering J, IJzermans JNM, Minnee RC. Ipsilateral Aorto-Iliac Calcification is Not Directly Associated With eGFR After Kidney Transplantation: A Prospective Cohort Study Analyzed Using a Linear Mixed Model. Transpl Int 2023; 36:10647. [PMID: 36756277 PMCID: PMC9901502 DOI: 10.3389/ti.2023.10647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 01/05/2023] [Indexed: 01/21/2023]
Abstract
Aorto-iliac calcification (AIC) is a well-studied risk factor for post-transplant cardiovascular events and mortality. Its effect on graft function remains unknown. The primary aim of this prospective cohort study was to assess the association between AIC and estimated glomerular filtration rate (eGFR) in the first year post-transplant. Eligibility criteria were: ≥50 years of age or ≥30 years with at least one risk factor for vascular disease. A non-contrast-enhanced CT-scan was performed with quantification of AIC using the modified Agatston score. The association between AIC and eGFR was investigated with a linear mixed model adjusted for predefined variables. One-hundred-and-forty patients were included with a median of 31 (interquartile range 26-39) eGFR measurements per patient. No direct association between AIC and eGFR was found. We observed a significant interaction between follow-up time and ipsilateral AIC, indicating that patients with higher AIC scores had lower eGFR trajectory over time starting 100 days after transplant (p = 0.014). To conclude, severe AIC is not directly associated with lower post-transplant eGFR. The significant interaction indicates that patients with more severe AIC have a lower eGFR trajectory after 100 days in the first year post-transplant.
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Affiliation(s)
- Elsaline Rijkse
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Joke I. Roodnat
- Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Sara J. Baart
- Department of Biostatistics, Erasmus Medical Center, Rotterdam, Netherlands
| | | | - Marcel L. Dijkshoorn
- Department of Radiology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Hendrikus J. A. N. Kimenai
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Jacqueline van de Wetering
- Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Jan N. M. IJzermans
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Robert C. Minnee
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, Netherlands,*Correspondence: Robert C. Minnee,
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12
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Erlandsson H, Qureshi AR, Ripsweden J, Haugen Löfman I, Söderberg M, Wennberg L, Lundgren T, Bruchfeld A, Brismar TB, Stenvinkel P. Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation. J Intern Med 2022; 291:813-823. [PMID: 35112417 PMCID: PMC9306575 DOI: 10.1111/joim.13459] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. METHODS In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. RESULTS Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. CONCLUSION Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.
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Affiliation(s)
- Helen Erlandsson
- Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.,Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Jonaz Ripsweden
- Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.,Unit of radiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Ida Haugen Löfman
- Section of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Magnus Söderberg
- Cardiovascular, Renal and Metabolism Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden
| | - Lars Wennberg
- Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Torbjörn Lundgren
- Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Annette Bruchfeld
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.,Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Torkel B Brismar
- Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.,Unit of radiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.,Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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13
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Guillén-Olmos E, Torregrosa JV, Garcia-Herrera A, Ganau S, Diekmann F, Cucchiari D. Development of calciphylaxis in kidney transplant recipients with a functioning graft. Clin Kidney J 2022; 15:663-671. [PMID: 35371461 PMCID: PMC8967679 DOI: 10.1093/ckj/sfab205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Indexed: 11/30/2022] Open
Abstract
Background Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in association with severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT). Methods Analysis of the local series of calciphylaxis after KT (n = 14) along with all the other cases reported in the literature from 1969 to 2019 (n = 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000). Results Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25–4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases. Conclusions Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied.
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Affiliation(s)
- Elena Guillén-Olmos
- Nephrology and Renal Transplantation Department, Hospital Clínic, Barcelona, Spain
| | | | | | - Sergi Ganau
- Radiology Department, Hospital Clínic, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and Renal Transplantation Department, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, Madrid, Spain
| | - David Cucchiari
- Nephrology and Renal Transplantation Department, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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14
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Molinari P, Alfieri CM, Mattinzoli D, Campise M, Cervesato A, Malvica S, Favi E, Messa P, Castellano G. Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects. Front Med (Lausanne) 2022; 9:821884. [PMID: 35360722 PMCID: PMC8960161 DOI: 10.3389/fmed.2022.821884] [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: 11/24/2021] [Accepted: 02/08/2022] [Indexed: 12/25/2022] Open
Abstract
Renal transplantation (RTx) allows us to obtain the resolution of the uremic status but is not frequently able to solve all the metabolic complications present during end-stage renal disease. Mineral and bone disorders (MBDs) are frequent since the early stages of chronic kidney disease (CKD) and strongly influence the morbidity and mortality of patients with CKD. Some mineral metabolism (MM) alterations can persist in patients with RTx (RTx-p), as well as in the presence of complete renal function recovery. In those patients, anomalies of calcium, phosphorus, parathormone, fibroblast growth factor 23, and vitamin D such as bone and vessels are frequent and related to both pre-RTx and post-RTx specific factors. Many treatments are present for the management of post-RTx MBD. Despite that, the guidelines that can give clear directives in MBD treatment of RTx-p are still missed. For the future, to obtain an ever-greater individualisation of therapy, an increase of the evidence, the specificity of international guidelines, and more uniform management of these anomalies worldwide should be expected. In this review, the major factors related to post-renal transplant MBD (post-RTx-MBD), the main mineral metabolism biochemical anomalies, and the principal treatment for post-RTx MBD will be reported.
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Affiliation(s)
- Paolo Molinari
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
| | - Carlo Maria Alfieri
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Deborah Mattinzoli
- Renal Research Laboratory Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
| | - Mariarosaria Campise
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
| | - Angela Cervesato
- Department of Nephrology, Clinical and Translational Sciences, Università degli Studi della Campania L.Vanvitelli, Naples, Italy
| | - Silvia Malvica
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
| | - Evaldo Favi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Department of General Surgery, Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Piergiorgio Messa
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Castellano
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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15
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Jang Y, Park S, Lee H, Kim YH, Lee JP, Park SK, Jung IM, Ha J, Lim CS, Kim YS, Kwon H, Kim YC. Prognostic Value of Pre- and Post-Serum Alkaline Phosphatase Among Renal Transplant Recipients. Transplant Proc 2022; 54:678-684. [DOI: 10.1016/j.transproceed.2022.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/01/2022] [Indexed: 12/01/2022]
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16
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Xu C, Smith ER, Tiong MK, Ruderman I, Toussaint ND. Interventions to Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials. J Am Soc Nephrol 2022; 33:1011-1032. [PMID: 35232774 PMCID: PMC9063901 DOI: 10.1681/asn.2021101327] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 02/16/2022] [Indexed: 11/03/2022] Open
Abstract
Background Vascular calcification is associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Evidence-based interventions that may attenuate its progression in CKD remain uncertain.
Methods We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compare with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method.
Results There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.
Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
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Affiliation(s)
- Chelsea Xu
- Department of Medicine, University of Melbourne, Parkville, Australia
| | - Edward R Smith
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Mark K Tiong
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Irene Ruderman
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Nigel D Toussaint
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
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17
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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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18
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Wu PY, Lee SY, Chang KV, Chao CT, Huang JW. Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review. Healthcare (Basel) 2021; 9:979. [PMID: 34442116 PMCID: PMC8394860 DOI: 10.3390/healthcare9080979] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/26/2021] [Accepted: 07/28/2021] [Indexed: 12/13/2022] Open
Abstract
Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.
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Affiliation(s)
- Patrick Yihong Wu
- School of Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan;
| | - Szu-Ying Lee
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
| | - Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan;
| | - Chia-Ter Chao
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan
| | - Jenq-Wen Huang
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
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19
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Long-Term Treatment of Azathioprine in Rats Induces Vessel Mineralization. Biomedicines 2021; 9:biomedicines9030327. [PMID: 33806932 PMCID: PMC8004774 DOI: 10.3390/biomedicines9030327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/14/2021] [Accepted: 03/17/2021] [Indexed: 12/31/2022] Open
Abstract
Medial vascular calcification (mVC) is closely related to cardiovascular disease, especially in patients suffering from chronic kidney disease (CKD). Even after successful kidney transplantation, cardiovascular mortality remains increased. There is evidence that immunosuppressive drugs might influence pathophysiological mechanisms in the vessel wall. Previously, we have shown in vitro that mVC is induced in vascular smooth muscle cells (VSMCs) upon treatment with azathioprine (AZA). This effect was confirmed in the current study in an in vivo rat model treated with AZA for 24 weeks. The calcium content increased in the aortic tissue upon AZA treatment. The pathophysiologic mechanisms involve AZA catabolism to 6-thiouracil via xanthine oxidase (XO) with subsequent induction of oxidative stress. Proinflammatory cytokines, such as interleukin (IL)-1ß and IL-6, increase upon AZA treatment, both systemically and in the aortic tissue. Further, VSMCs show an increased expression of core-binding factor α-1, alkaline phosphatase and osteopontin. As the AZA effect could be decreased in NLRP3−/− aortic rings in an ex vivo experiment, the signaling pathway might be, at least in part, dependent on the NLRP3 inflammasome. Although human studies are necessary to confirm the harmful effects of AZA on vascular stiffening, these results provide further evidence of induction of VSMC calcification under AZA treatment and its effects on vessel structure.
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20
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Dai L, Li L, Erlandsson H, Jaminon AMG, Qureshi AR, Ripsweden J, Brismar TB, Witasp A, Heimbürger O, Jørgensen HS, Barany P, Lindholm B, Evenepoel P, Schurgers LJ, Stenvinkel P. Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study. PLoS One 2021; 16:e0247623. [PMID: 33626087 PMCID: PMC7904143 DOI: 10.1371/journal.pone.0247623] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/09/2021] [Indexed: 12/21/2022] Open
Abstract
Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.
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Affiliation(s)
- Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Longkai Li
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Nephrology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Helen Erlandsson
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Armand M. G. Jaminon
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Torkel B. Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Anna Witasp
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Hanne Skou Jørgensen
- Department of Microbiology Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven-University of Leuven, Leuven, Belgium
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Pieter Evenepoel
- Department of Microbiology Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven-University of Leuven, Leuven, Belgium
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Leon J. Schurgers
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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21
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Podestà MA, Cucchiari D, Ciceri P, Messa P, Torregrosa JV, Cozzolino M. Cardiovascular calcifications in kidney transplant recipients. Nephrol Dial Transplant 2021; 37:2063-2071. [PMID: 33620476 DOI: 10.1093/ndt/gfab053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Vascular and valvular calcifications are highly prevalent in kidney transplant recipients and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uremia-associated metabolic derangements, kidney transplant recipients are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in kidney transplant recipients, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.
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Affiliation(s)
- Manuel Alfredo Podestà
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
| | - David Cucchiari
- Nephrology and Renal Transplant Department, Hospital Clínic, Barcelona, Spain
| | - Paola Ciceri
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Piergiorgio Messa
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
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22
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Hassanein M, Abdelfattah OM, Saad AM, Isogai T, Gad MM, Ahuja KR, Ahmed T, Shekhar S, Fatica R, Poggio E, Kapadia SR. Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Kidney Transplant Recipients: A Nationwide Representative Study. STRUCTURAL HEART 2021. [DOI: 10.1080/24748706.2020.1845918] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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23
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Denosumab Recovers Aortic Arch Calcification During Long-Term Hemodialysis. Kidney Int Rep 2020; 6:605-612. [PMID: 33732975 PMCID: PMC7938059 DOI: 10.1016/j.ekir.2020.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/21/2020] [Accepted: 12/08/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction Aortic arch calcification (AoAC) is related closely to mortality risk in patients undergoing maintenance dialysis. Recent experimentally obtained data suggest that osteoprotegerin/receptor activator for nuclear factor κB ligand signal transmission plays a role in de novo chondrogenic transition of vascular cells leading to calcification that is unrelated to bone metabolism. This study investigated the long-term effects of denosumab, an osteoprotegerin mimic peptide, on AoAC. Methods This study examined 58 patients with an 8 year vintage of dialysis at 1 center for observational study during 2009 to 2020. Denosumab was administered to 28 patients every 6 months. Blood chemical data were used. AoAC proportions were measured using a simple but computed tomography–equivalent computer-based chest X-ray analysis (calcified pieces of areas around the aorta). Results Blood chemical data of the control and denosumab groups that did not differ at the start showed differences of mineral metabolism after 30 months of observation. Remarkably, the AoAC proportion increased from 29.4% to 46.25% in the control group but decreased significantly from 25.0% to 20.0% (P < 0.01) in the denosumab group. Denosumab effects on decalcification were not observed 12 months after initiation. Conclusion We conclude that long-term use of denosumab is effective to reverse or treat AoAC in patients undergoing hemodialysis.
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24
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Bamoulid J, Frimat M, Courivaud C, Crepin T, Gaiffe E, Hazzan M, Ducloux D. A simple score to predict early death after kidney transplantation. Eur J Clin Invest 2020; 50:e13312. [PMID: 32533894 DOI: 10.1111/eci.13312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 06/02/2020] [Accepted: 06/02/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Few studies have focused on risk stratification for premature death after transplantation. However, stratification of individual risk is an essential step in personalized care. MATERIAL AND METHODS We have developed a risk score of early post-transplant death (ORLY score) in a prospective multicentre cohort including 942 patients and validated our model in a retrospective independent replication cohort including 874 patients. RESULTS 60 patients (6.4%) from the prospective cohort died during the first three-year post-transplant. Age, male gender, diabetes, dialysis duration and chronic respiratory failure were associated with early post-transplant death. The multivariable model exhibited good discrimination ability (C-index = 0.78, 95%CI [0.75-0.81]). ORLY score highly predicted early death after transplantation (1.34; 95%CI, 1.22 to 1.48 for each increase of 1 point in score; P < .001). The predictive value of the score in the validation cohort was close to that observed in the experimental cohort (1.41; 95%CI, 1.27 to 1.56 for each increase of 1 point in score; P < .001). Merging the two cohorts, four categories of risk could be individualized: low, 0-5 (n = 522, mean risk, 1%); intermediate, 6-7 (n = 739, mean risk 4.7%); moderate, 8-10 (n = 429, mean risk 10%); and high risk 11-15 (n = 132, mean risk 19%). CONCLUSIONS The ORLY score discriminates patients with high risk of early death.
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Affiliation(s)
- Jamal Bamoulid
- INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France.,Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France
| | - Marie Frimat
- Service de Néphrologie - CHRU de Lille - Université de Lille - UMR 995, Lille, France
| | - Cécile Courivaud
- INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France.,Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France
| | - Thomas Crepin
- INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France.,Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France
| | - Emilie Gaiffe
- INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France
| | - Marc Hazzan
- Service de Néphrologie - CHRU de Lille - Université de Lille - UMR 995, Lille, France
| | - Didier Ducloux
- INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France.,Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France
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25
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Alappan HR, Vasanth P, Manzoor S, O'Neill WC. Vascular Calcification Slows But Does Not Regress After Kidney Transplantation. Kidney Int Rep 2020; 5:2212-2217. [PMID: 33305114 PMCID: PMC7710884 DOI: 10.1016/j.ekir.2020.09.039] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Introduction Medial arterial calcification is a common and progressive lesion in end-stage renal disease that is associated with poor cardiovascular outcomes. Whether this lesion can be arrested or reversed is unknown, and was examined retrospectively by measuring progression of breast arterial calcification before and after kidney transplantation. Methods Arterial calcification was measured on serial mammograms from patients with previous kidney transplantation and compared to measurements performed before transplantation or in patients on the active waitlist. Serum creatinine >2.0 mg/dl after transplantation or warfarin use were exclusions. Results Median (interquartile range) progression of arterial calcification was 12.9 mm/breast per year (5.9 to 32.6) in 34 patients before or awaiting transplantation compared to just 1.2 mm/breast per year (-0.54 to 5.1) in 34 patients after transplantation (P < 0.001). Slowing of progression was also seen in longitudinal analyses of patients with mammograms performed both before and after transplantation. Duration of end-stage renal disease before transplantation but not age, diabetes, baseline calcification, or serum chemistries correlated with progression after transplantation. Significant regression was not observed in any patient. Conclusion In this first quantitative study of the effect of kidney transplantation, medial arterial calcification appeared to slow to rates seen in patients with normal renal function, indicating that the effect of renal failure may be completely abrogated. Overall, however, there was no significant regression, suggesting that calcification is irreversible and emphasizing the importance of prevention. Duration of pretransplant end-stage renal disease but not baseline calcification was a determinant of progression, consistent with cumulative, permanent changes to arteries that promote calcification.
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Affiliation(s)
- Harish R Alappan
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Payaswini Vasanth
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Shumila Manzoor
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - W Charles O'Neill
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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26
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Benjamens S, Rijkse E, te Velde-Keyzer CA, Berger SP, Moers C, de Borst MH, Yakar D, Slart RHJA, Dor FJMF, Minnee RC, Pol RA. Aorto-Iliac Artery Calcification Prior to Kidney Transplantation. J Clin Med 2020; 9:2893. [PMID: 32906789 PMCID: PMC7563260 DOI: 10.3390/jcm9092893] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/03/2020] [Accepted: 09/04/2020] [Indexed: 12/14/2022] Open
Abstract
As vascular calcification is common in kidney transplant candidates, aorto-iliac vessel imaging is performed for surgical planning. The aim of the present study was to investigate whether a novel non-contrast enhanced computed tomography-based quantification technique for aorto-iliac calcification can be used for cardiovascular risk stratification prior to kidney transplantation. In this dual-center cohort study, we measured the aorto-iliac calcium score (CaScore) of 547 patients within three years prior to transplantation (2005-2018). During a median (interquartile range) follow-up of 3.1 (1.4, 5.2) years after transplantation, 80 (14.7%) patients died, of which 32 (40.0%) died due to cardiovascular causes, and 84 (15.5%) patients had a cardiovascular event. Kaplan-Meier survival curves showed significant differences between the CaScore tertiles for cumulative overall-survival (Log-rank test p < 0.0001), cardiovascular survival (p < 0.0001), and cardiovascular event-free survival (p < 0.001). In multivariable Cox regression, the aorto-iliac CaScore was associated with all-cause mortality (hazard ratio 1.53, 95%CI 1.14-2.06, p = 0.005), cardiovascular mortality (2.04, 1.20-3.45, p = 0.008), and cardiovascular events (1.35, 1.01-1.80, p = 0.042). These independent associations of the aorto-iliac CaScore with the outcome measures can improve the identification of patients at risk for (cardiovascular) death and those who could potentially benefit from stringent cardiovascular monitoring to improve their prognosis after transplantation.
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Affiliation(s)
- Stan Benjamens
- Department of Surgery, Division of Transplant Surgery, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.M.); (R.A.P.)
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging & Department of Radiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (D.Y.); (R.H.J.A.S.)
| | - Elsaline Rijkse
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, 3015 CE Rotterdam, The Netherlands; (E.R.); (R.C.M.)
| | - Charlotte A. te Velde-Keyzer
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.A.t.V.-K.); (S.P.B.); (M.H.d.B.)
| | - Stefan P. Berger
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.A.t.V.-K.); (S.P.B.); (M.H.d.B.)
| | - Cyril Moers
- Department of Surgery, Division of Transplant Surgery, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.M.); (R.A.P.)
| | - Martin H. de Borst
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.A.t.V.-K.); (S.P.B.); (M.H.d.B.)
| | - Derya Yakar
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging & Department of Radiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (D.Y.); (R.H.J.A.S.)
| | - Riemer H. J. A. Slart
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging & Department of Radiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (D.Y.); (R.H.J.A.S.)
- Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands
| | - Frank J. M. F. Dor
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK;
- Department of Surgery & Cancer, Imperial College, London SW7 2BU, UK
| | - Robert C. Minnee
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, 3015 CE Rotterdam, The Netherlands; (E.R.); (R.C.M.)
| | - Robert A. Pol
- Department of Surgery, Division of Transplant Surgery, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (C.M.); (R.A.P.)
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27
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Candellier A, Hénaut L, Morelle J, Choukroun G, Jadoul M, Brazier M, Goffin É. Aortic stenosis in patients with kidney failure: Is there an advantage for a PD-first policy? Perit Dial Int 2020; 41:158-167. [DOI: 10.1177/0896860820941371] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Aortic stenosis (AS) is the most common valvular disease. It is twice as prevalent in patients with kidney failure as compared to the general population. In addition, AS progresses at a faster rate and is associated with a higher risk of death and poorer quality of life in patients on dialysis. Chronic kidney disease–mineral and bone disorder (CKD-MBD), inflammation, and hemodynamic disturbances contribute to the pathophysiology and progression of AS. Whether the type of dialysis modality, that is, hemodialysis (HD) versus peritoneal dialysis (PD), has a differential impact on the development and progression of AS in patients with kidney failure remains debated. Recent data indicate that the prevalence of valvular calcifications might be lower and the development of AS delayed in PD patients, as compared to those treated with HD. This could be accounted for by several mechanisms including reduced valvular shear stress, better preservation of residual kidney function (with better removal of protein-bound uremic toxins and CKD-MBD profile), and lower levels of systemic inflammation. Given the high morbidity and mortality rates related to interventional procedures in the population with kidney failure, surgical and transcatheter aortic valve replacement should be considered in selected patients with severe AS. Strategies slowing down the progression of aortic valve remodeling should remain the cornerstone in the management of individuals with kidney failure and mild to moderate AS. This review explores the potential benefits of PD in patients with kidney failure and AS and provides some clues to help clinicians in the decision-making process when options for kidney replacement therapy are considered in patients with AS.
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Affiliation(s)
- Alexandre Candellier
- Division of Nephrology, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
- UR UPJV 7517, MP3CV, CURS, Amiens, France
- Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | | | - Johann Morelle
- Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Gabriel Choukroun
- Division of Nephrology, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
- UR UPJV 7517, MP3CV, CURS, Amiens, France
| | - Michel Jadoul
- Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | | | - Éric Goffin
- Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
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Pereira L, Frazão JM. The bone-vessel axis in chronic kidney disease: An update on biochemical players and its future role in laboratory medicine. Clin Chim Acta 2020; 508:221-227. [PMID: 32422129 DOI: 10.1016/j.cca.2020.05.023] [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: 02/16/2020] [Revised: 03/31/2020] [Accepted: 05/11/2020] [Indexed: 12/16/2022]
Abstract
Vascular wall calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). In CKD, VC is more frequent and severe than in the general population and it is associated with increased cardiovascular mortality and morbidity. In the last years, laboratory and clinical evidence have drawn the attention to the relationship between bone disease and VC in CKD patients, leading to the concept of a bone-vessel or bone-vascular axis. It means that disorders of bone volume and bone turnover may influence the risk of VC and ultimately the high risk of cardiovascular mortality. In fact, a higher burden of VC has been associated to low bone volume and low bone turnover in hemodialysis (HD) patients with renal osteodystrophy characterized by histomorphometric evaluation of bone biopsies. The molecular mechanisms underlying the regulation of bone cells and vascular cells in CKD are poorly understood. In this review, we discuss relevant evidence linking bone disorders and VC in CKD and also rising molecular players involved in this bone-vascular axis. Indeed, accumulating data is available for two proposed systems: receptor activator for nuclear factor kB (RANK)/ RANK ligand (RANKL)/osteoprotegerin (OPG) system and inhibitors of Wnt signaling - mainly sclerostin. Although they are promising biochemical markers linking bone formation and bone reabsorption with VC, there is a long way to go as long evidence from laboratory studies is often divergent to the clinical data as will be discussed. Future prospective studies are needed in order to evaluate the role of these biochemical players as useful clinical markers for VC, bone volume and perhaps bone turnover.
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Affiliation(s)
- Luciano Pereira
- Institute of Investigation and Innovation in Health, University of Porto, Portugal; INEB - National Institute of Biomedical Engineering, University of Porto, Portugal; Department of Nephrology, São João Hospital Center, Porto, Portugal
| | - João M Frazão
- Institute of Investigation and Innovation in Health, University of Porto, Portugal; INEB - National Institute of Biomedical Engineering, University of Porto, Portugal; Department of Nephrology, São João Hospital Center, Porto, Portugal.
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Marchelek-Myśliwiec M, Dziedziejko V, Nowosiad-Magda M, Wiśniewska M, Safranow K, Pawlik A, Domański L, Dołęgowska K, Dołęgowska B, Stępniewska J, Ciechanowski K. Bone Metabolism Parameters in Hemodialysis Patients With Chronic Kidney Disease and in Patients After Kidney Transplantation. Physiol Res 2019; 68:947-954. [PMID: 31647290 DOI: 10.33549/physiolres.934118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease adversely affects the structure and metabolism of bone tissue, which may be a result of disturbed biochemical processes in adipose tissue. Renal replacement therapy is a life-saving therapy but it does not restore all metabolic functions and sometimes even escalates some disturbances. The study included 126 subjects: 47 hemodialysis patients (HD), 56 patients after renal transplantation (Tx) and 23 healthy controls (K). Bone density at the femoral neck (FN) and lumbar spine (LS), as well as body composition (adipose tissue content and lean body mass) were measured in each patient using the DXA method. In addition, serum concentrations of glucose, calcium, phosphorus, parathormone, FGF23, Klotho, osteocalcin, leptin, adiponectin and 1,25-dihydroxyvitamin D3 were measured. We observed significantly higher concentrations of leptin, FGF23 and Klotho proteins in the HD patients (77.2±48.1 ng/ml, 54.7±12.4 pg/ml, 420.6±303.8 ng/ml, respectively) and the Tx group (33.2±26.5 ng/ml; 179.8±383.9 pg/ml; 585.4±565.7, respectively) compared to the control group (24.4±24.6 ng/ml, 43.3±37.3 pg/ml, 280.5±376.0 ng/ml). Significantly lower bone density at FN was observed in the HD and Tx patients in comparison to the controls and in the HD patients compared to the Tx group. There were no significant differences in body mass composition between the studied groups. The results of this study indicate that both hemodialysis and transplantation are associated with increased serum concentrations of leptin, FGF23 and Klotho proteins, as well as lower bone density at femoral neck.
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Affiliation(s)
- M Marchelek-Myśliwiec
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
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Santos AH, Chen C, Alquadan K, Wen X. Outcomes of sirolimus regimens in 65-year-old and older kidney transplant recipients: a registry-based observational study. Int Urol Nephrol 2019; 51:2063-2072. [PMID: 31385180 DOI: 10.1007/s11255-019-02251-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 07/29/2019] [Indexed: 11/29/2022]
Abstract
PURPOSE In large observational studies of adult kidney transplant recipients (KTRs) where older adults (65 years old and older) were not well represented, the mammalian target of rapamycin inhibitors (mTOR inhibitors) has poorer outcomes than the standard tacrolimus-mycophenolate-steroids (TAC-MPA-S) regimen. We conducted this study to compare the outcomes of regimens containing the common mTOR inhibitor, sirolimus (SRL) against TAC-MPA-S in older adult KTRs. METHODS Using the 2000-2016 Scientific Registry of Transplant Recipients, Cox multivariable regression models were conducted to analyze the patient and graft outcomes associated with regimens containing SRL, steroids (S) and cyclosporine (CSA), tacrolimus (TAC), or mycophenolate (MPA) vs. the standard (TAC-MPA-S) regimen in older adult KTRs. RESULTS Included in the analysis were 15,008 (95.19%) older adult KTRs on standard (TAC-MPA-S) regimen, 242 (1.53%) on SRL-MPA-S, 300 (1.90%) on SRL-TAC-S, and 217 (1.38%) on SRL-CSA-S. Compared with the standard regimen, the adjusted risks of all-cause death and overall graft loss over a maximum 5-year follow-up were highest with SRL-MPA-S, intermediate with SRL-TAC-S and not significantly different with SRL-CSA-S. The adjusted risks of all-cause death and overall graft loss were modified by a pre-transplant history of malignancy in older adult KTRs on SRL-TAC-S, not in those on SRL-MPA-S or SRL-CSA-S. CONCLUSIONS In older adult kidney transplant recipients, SRL-TAC-S or SRL-MPA-S, but not SRL-CSA-S is associated with higher risks of death and allograft loss than standard TAC-MPA-S regimen and a pre-transplant malignancy history worsens these risks in patients on SRL-TAC-S. Confirmation of our findings by a prospective randomized trial is needed before translation into clinical practice can be recommended.
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Affiliation(s)
- Alfonso H Santos
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg, NG-4, Gainesville, FL, 32610, USA.
| | - Chao Chen
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Kawther Alquadan
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg, NG-4, Gainesville, FL, 32610, USA
| | - Xuerong Wen
- Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
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Naganuma T, Takemoto Y, Uchida J, Nakatani T, Kabata D, Shintani A. Hypercalcemia Is a Risk Factor for the Progression of Aortic Calcification in Kidney Transplant Recipients. Kidney Blood Press Res 2019; 44:823-834. [PMID: 31266041 DOI: 10.1159/000501740] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. MATERIALS This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. RESULTS The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). CONCLUSION The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.
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Affiliation(s)
- Toshihide Naganuma
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan,
| | - Yoshiaki Takemoto
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Junji Uchida
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tatsuya Nakatani
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ayumi Shintani
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
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McMahon M, Skaggs B, Grossman J, Wong WK, Sahakian L, Chen W, Hahn B. Comparison of PREDICTS atherosclerosis biomarker changes after initiation of new treatments in patients with SLE. Lupus Sci Med 2019; 6:e000321. [PMID: 31321062 PMCID: PMC6606066 DOI: 10.1136/lupus-2019-000321] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 05/21/2019] [Accepted: 05/29/2019] [Indexed: 12/21/2022]
Abstract
Objective Patients with SLE have an increased risk of atherosclerosis (ATH) that is not adequately explained by traditional risk factors. We previously described the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular disease in PaTients with SLE (PREDICTS) atherosclerosis-risk panel, which includes proinflammatory HDL (piHDL), leptin, soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and homocysteine, as well as age and diabetes. A high PREDICTS score confers 28-fold increased odds for future atherosclerosis in SLE. The aim of this study is to determine whether PREDICTS biomarkers are modifiable by common lupus therapies. Methods This prospective observational study included SLE subjects started on new lupus treatments. Leptin, sTWEAK, homocysteine and antioxidant function of HDL were measured at baseline (prior to drug initiation), 6 weeks and 12 weeks. Results 16 subjects started mycophenolate (MMF), 18 azathioprine (AZA) and 25 hydroxychloroquine (HCQ). In MMF-treated subjects, HDL function progressively improved from 2.23 ± 1.32 at baseline to 1.37±0.81 at 6 weeks (p=0.02) and 0.93±0.54 at 12 weeks (p=0.009). sTWEAK levels also improved in MMF-treated subjects from 477.5±447.1 to 290.3±204.6 pg/mL after 12 weeks (p=0.04), but leptin and homocysteine levels were not significantly changed. In HCQ-treated subjects, only HDL function improved from 1.80±1.29 at baseline to 1.03±0.74 after 12 weeks (p=0.05). There were no changes in the AZA group. MMF treatment was still associated with significant improvements in HDL function after accounting for potential confounders such as total prednisone dose and changes in disease activity. Overall, the mean number of high-risk PREDICTS biomarkers at week 12 significantly decreased in the entire group of patients started on a new lupus therapy (2.1±0.9 to 1.8±0.9, p=0.02) and in the MMF-treated group (2.4±0.8 vs 1.8±0.9, p=0.003), but not in the AZA or HCQ groups. In multivariate analysis, the odds of having a high PREDICTS atherosclerosis risk score at 12 weeks were lower with MMF treatment (OR 0.002, 95% CI 0.000 to 0.55, p=0.03). Conclusions 12 weeks of MMF therapy improves the overall PREDICTS atherosclerosis biomarker profile. Further studies will determine whether biomarker changes reflect decreases in future cardiovascular events.
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Affiliation(s)
- Maureen McMahon
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Brian Skaggs
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Jennifer Grossman
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Weng Kee Wong
- Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA
| | - Lori Sahakian
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Weiling Chen
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Bevra Hahn
- Internal Medicine, Division Rheumatology, University of California, Los Angeles, Los Angeles, California, USA
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Long-term evaluation of coronary artery calcifications in kidney transplanted patients: a follow up of 5 years. Sci Rep 2019; 9:6869. [PMID: 31053792 PMCID: PMC6499881 DOI: 10.1038/s41598-019-43216-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 04/17/2019] [Indexed: 12/13/2022] Open
Abstract
Coronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0–233]. At T5 AS was 119 [1–413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs.
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Jansz TT, Verhaar MC, London GM, van Jaarsveld BC. Is progression of coronary artery calcification influenced by modality of renal replacement therapy? A systematic review. Clin Kidney J 2018; 11:353-361. [PMID: 29942499 PMCID: PMC6007793 DOI: 10.1093/ckj/sfx124] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 09/12/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Progression of coronary artery calcification is an important marker for cardiovascular morbidity in end-stage renal disease patients. Therefore, we reviewed the evidence on coronary artery calcification progression in different renal replacement therapies. METHODS MEDLINE (PubMed), Embase and TRIP databases were searched from 1999 - 2016. Additionally, bibliographies were searched by hand and citation tracking of key publications was performed. Prospective studies were included that examined coronary artery calcification with two or more multislice computed tomography scans ≥6 months apart in patients 18-75 years old receiving any renal replacement therapy, including kidney transplantation. Reporting of separate scores for different modalities was required. Two researchers extracted data independently with pilot-tested forms and assessed the risk of bias using a validated tool. RESULTS We identified 29 eligible studies that assessed coronary artery calcification progression in end-stage renal disease patients, of which 19 studies evaluated haemodialysis and 8 kidney transplantation. Evidence on progression in peritoneal dialysis (three studies) and nocturnal haemodialysis (one study) was limited. Meta-analysis was not possible due to diverse reporting methods of coronary artery calcification scores and definitions of progression. Median coronary artery calcification scores were considerably higher in haemodialysis cohorts at baseline, presumably due to a generally higher age and dialysis vintage. Median coronary artery calcification progressed universally. Visual inspection suggested the least progression in kidney transplant recipients. CONCLUSIONS There is insufficient evidence to compare the influence of renal replacement therapies on coronary artery calcification progression. We advocate the adoption of a standardized reporting method of coronary artery calcification progression.
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Affiliation(s)
- Thijs T Jansz
- Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Marianne C Verhaar
- Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Gérard M London
- INSERM U970, Hôpital Européen Georges Pompidou, Paris, France
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Piotti G, Gandolfini I, Palmisano A, Maggiore U. Metabolic risk profile in kidney transplant candidates and recipients. Nephrol Dial Transplant 2018; 34:388-400. [DOI: 10.1093/ndt/gfy151] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 05/01/2018] [Indexed: 12/30/2022] Open
Affiliation(s)
- Giovanni Piotti
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Ilaria Gandolfini
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alessandra Palmisano
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Umberto Maggiore
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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Laucyte-Cibulskiene A, Boreikaite E, Aucina G, Gudynaite M, Rudminiene I, Anisko S, Vareikiene L, Gumbys L, Valanciene D, Ryliskyte L, Strupas K, Rimsevicius L, Miglinas M. Usefulness of pretransplant aortic arch calcification evaluation for kidney transplant outcome prediction in one year follow-up. Ren Fail 2018; 40:201-208. [PMID: 29619867 PMCID: PMC6014335 DOI: 10.1080/0886022x.2018.1455588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Vascular calcification (VC) is linked to post-transplant cardiovascular events and hypercalcemia which may influence kidney graft function in the long term. We aimed to evaluate whether pretransplant aortic arch calcification (AoAC) can predict post-transplant cardiovascular or cerebrovascular events (CVEs), and to assess its association with post-transplant plasma calcium levels and renal function in one-year follow-up. Our single-center observational prospective study enrolled 37 kidney transplant recipients (KTR) without previous history of vascular events. Two radiologists evaluated pretransplant AoAC on chest X-ray as suggested by Ogawa et al. in 2009. Cohen’s kappa coefficient was 0.71. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry before and one year after transplantation. Patient clinical, biochemical data, and cardiovascular/CVE rate were monitored within 1 year. We found out that eGFR1year correlated with eGFRdischarge and calcium based on hospital discharge data (β = 0.563, p = .004 and β = 51.360, p = .026, respectively). Multivariate linear regression revealed that donor age, donor gender, and recipient eGFRdischarge (R-squared 0.65, p = .002) better predict eGFR1year than AoAC combined with recipient eGFRdischarge (R-squared 0.35, p = .006). During 1-year follow-up, four (10.81%) patients experienced cardiovascular events, which were predicted by PWV ratio (HR 7.549, p = .045), but not related to AoAC score (HR 1.044, p = .158). In conclusion, KTR without previous vascular events have quite low cardiovascular/CVE rate within 1-year follow-up. VC evaluated as AoAC on pretransplant chest X-ray together with recipient eGFRdischarge could be related to kidney function in one-year follow-up.
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Affiliation(s)
- Agne Laucyte-Cibulskiene
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | | | - Gediminas Aucina
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania
| | - Migle Gudynaite
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Ilona Rudminiene
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Sigita Anisko
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Loreta Vareikiene
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Liutauras Gumbys
- d Centre of Radiology and Nuclear Medicine , Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Dileta Valanciene
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania.,d Centre of Radiology and Nuclear Medicine , Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Ligita Ryliskyte
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania
| | - Kestutis Strupas
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | - Laurynas Rimsevicius
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | - Marius Miglinas
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
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Kim DH, Lee KC, Han SY. Cyclosporin A Aggravates Calcification of Vascular Smooth Muscle Cells Under High-Glucose Conditions with a Calcifying Medium. Ann Transplant 2018; 23:112-118. [PMID: 29434184 PMCID: PMC6248036 DOI: 10.12659/aot.908168] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Vascular calcification (VC) progresses substantially even after kidney transplantation, and is a predictor of morbidity and mortality. However, the effect of cyclosporin A (CsA) on VC has not been reported in diabetic kidney transplant patients. In this study, we evaluated the effect of CsA on the VC of mouse vascular smooth muscle cells (VSMCs) under high glucose (HG). MATERIAL AND METHODS To demonstrate the effect of CsA (1.0 µmol/L) and HG (30 mM) in the induction of the VC of the VSMCs, we determined alkaline phosphatase (ALP) activity, microscopic morphology of calcification, the expressions of the calcification and inflammation-related genes, and the intracellular calcium concentrations in VSMCs. RESULTS Calcification was observed 14 days after exposure to a calcifying medium (sodium phosphate monobasic and dibasic mixture). On microscopic morphology, CsA alone did not induce calcification under HG conditions, but clearly increased calcification under HG with a calcifying medium. ALP activity increased under HG with CsA or a calcifying medium compared to HG conditions alone. CsA increased ALP activity under low glucose (LG, 5.5 mM) with a calcifying medium, but markedly increased under HG with a calcifying medium. CsA significantly increased the mRNA expressions of the calcification markers (core binding factor-alpha 1, bone morphologic proteins 2) as well as those of the inflammatory marker (interleukin 6), under HG with a calcifying medium. Intracellular calcium concentrations were unchanged in CsA alone but significantly increased with the presence of a calcifying medium under both LG and HG conditions. CONCLUSIONS Considering the effect of CsA on VC, the vascular adverse effects of CsA need to be verified in diabetic transplant patients in the future.
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Affiliation(s)
- Dae Hee Kim
- Clinical Research Center, Inje University, Ilsan-Paik Hosptial, Goyang, South Korea
| | - Keon Cheol Lee
- Department of Urology, Inje University Ilsan-Paik Hospital, Goyang, South Korea
| | - Sang Youb Han
- Clinical Research Center, Inje University, Ilsan-Paik Hosptial, Goyang, South Korea.,Division of Nephrology, Department of Internal Medicine, Inje University, Ilsan-Paik Hosptial, Goyang, South Korea
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Wyatt CM, Drueke TB. Vascular calcification in chronic kidney disease: here to stay? Kidney Int 2017; 92:276-278. [DOI: 10.1016/j.kint.2017.05.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 05/15/2017] [Indexed: 11/25/2022]
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Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link. Am J Med Sci 2017; 354:7-16. [DOI: 10.1016/j.amjms.2017.01.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 12/20/2016] [Accepted: 01/09/2017] [Indexed: 12/31/2022]
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40
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Park W, Park S, Han S. Long-term Clinical Outcome of Aortic Arch Calcification in Kidney Transplant Recipients. Transplant Proc 2017; 49:1027-1032. [DOI: 10.1016/j.transproceed.2017.03.072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Cianciolo G, Capelli I, La Manna G. Vitamin D-FGF-23 axis in kidney transplant recipients. Clin Transplant 2017; 31. [PMID: 28470796 DOI: 10.1111/ctr.12973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Giuseppe Cianciolo
- Department of Experimental, Diagnostic, Specialty Medicine, Nephrology, Dialysis, and Renal Transplant Unit, S. Orsola University Hospital, Bologna, Italy
| | - Irene Capelli
- Department of Experimental, Diagnostic, Specialty Medicine, Nephrology, Dialysis, and Renal Transplant Unit, S. Orsola University Hospital, Bologna, Italy
| | - Gaetano La Manna
- Department of Experimental, Diagnostic, Specialty Medicine, Nephrology, Dialysis, and Renal Transplant Unit, S. Orsola University Hospital, Bologna, Italy
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Chen NC, Hsu CY, Chen CL. The Strategy to Prevent and Regress the Vascular Calcification in Dialysis Patients. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9035193. [PMID: 28286773 PMCID: PMC5329685 DOI: 10.1155/2017/9035193] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 01/17/2017] [Indexed: 12/31/2022]
Abstract
The high prevalence of arterial calcification in end-stage renal disease (ESRD) is far beyond the explanation by common cardiovascular risk factors such as aging, diabetes, hypertension, and dyslipidemia. The finding relies on the fact that vascular and valvular calcifications are predictors of cardiovascular diseases and mortality in persons with chronic renal failure. In addition to traditional cardiovascular risk factors such as diabetes mellitus and blood pressure control, other ESRD-related risks such as phosphate retention, excess calcium, and prolonged dialysis time also contribute to the development of vascular calcification. The strategies are to reverse "calcium paradox" and lower vascular calcification by decreasing procalcific factors including minimization of inflammation (through adequate dialysis and by avoiding malnutrition, intravenous labile iron, and positive calcium and phosphate balance), correction of high and low bone turnover, and restoration of anticalcification factor balance such as correction of vitamin D and K deficiency; parathyroid intervention is reserved for severe hyperparathyroidism. The role of bone antiresorption therapy such as bisphosphonates and denosumab in vascular calcification in high-bone-turnover disease remains unclear. The limited data on sodium thiosulfate are promising. However, if calcification is to be targeted, ensure that bone health is not compromised by the treatments.
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Affiliation(s)
- Nai-Ching Chen
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
| | - Chih-Yang Hsu
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Liang Chen
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Chen Z, Qureshi AR, Parini P, Hurt-Camejo E, Ripsweden J, Brismar TB, Barany P, Jaminon AM, Schurgers LJ, Heimbürger O, Lindholm B, Stenvinkel P. Does statins promote vascular calcification in chronic kidney disease? Eur J Clin Invest 2017; 47:137-148. [PMID: 28036114 DOI: 10.1111/eci.12718] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 12/28/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. MATERIALS AND METHODS In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism. RESULTS Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins. CONCLUSION Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.
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Affiliation(s)
- Zhimin Chen
- Kidney Disease Center, First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, China.,Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Paolo Parini
- Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Metabolism Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Eva Hurt-Camejo
- Translational Science, CVMD iMed, AstraZeneca R&D, Gothenburg, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.,Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.,Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Armand M Jaminon
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
| | - Leon J Schurgers
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Patterns of Care and Outcomes in Cardiovascular Disease After Kidney Transplantation in the United States. Transplant Direct 2017; 3:e126. [PMID: 28361110 PMCID: PMC5367743 DOI: 10.1097/txd.0000000000000640] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 11/30/2016] [Indexed: 01/19/2023] Open
Abstract
Background Cardiovascular disease (CVD) is an important driver of mortality after kidney transplantation. Its broader impact on posttransplant health care utilization in US hospitals is unknown. Methods We used administrative claims data from the Nationwide Inpatient Sample and the American Hospital Association Annual Survey to identify hospitalizations for kidney transplant patients with a cardiovascular diagnosis from 2005 to 2011. CVD hospitalizations were stratified by transplant hospital status to characterize patterns in inpatient health care utilization and outcomes. Based on these analyses, the domestic burden of treatment for posttransplant CVD (myocardial infarction, stroke, congestive heart failure, dysrhythmia, cardiac arrest, malignant hypertension) was estimated. Results The total domestic burden of post-kidney transplant hospitalization between 2005 and 2011 is estimated at 389 138 of which 26.5% of episodes were related to CVD (n = 103 118). CVD was responsible for a growing proportion of post-transplant hospitalizations over time (24.4%-30.4%, P < 0.001). Compared with nontransplant hospitals, transplant hospitals had similar length of stay (median length of stay, 3.7 days), higher median costs per hospitalization (US $10 364 vs US $8606, overall US $9324), and lower adjusted mortality (3.2% vs 3.9%, overall 3.6%; P = 0.003). Conclusions Inpatient CVD care is increasing over time for kidney transplant patients, accounting for 30% of all post-transplant hospitalizations. Variation exists in the inpatient care, outcomes, and costs between by hospital type. Further studies are needed to better understand the mechanisms behind these phenomena.
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Lomashvili KA, Manning KE, Weitzmann MN, Nelea V, McKee MD, O'Neill WC. Persistence of Vascular Calcification after Reversal of Uremia. THE AMERICAN JOURNAL OF PATHOLOGY 2016; 187:332-338. [PMID: 27939134 DOI: 10.1016/j.ajpath.2016.10.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 10/14/2016] [Accepted: 10/18/2016] [Indexed: 11/26/2022]
Abstract
The extent to which vascular calcification is reversible and the possible mechanisms are unclear. To address this, calcified aortas from uremic mice were transplanted orthotopically into normal mice, and the calcium content, histology, and minerals of the allografts were compared with the nontransplanted donor aorta. Calcium content decreased immediately after transplantation but remained constant thereafter, with 68% ± 12% remaining after 34 weeks. X-ray diffraction showed the presence of apatite in both donor aortas and allografts. Osteoclasts were absent in the allografts and there was no expression of the macrophage marker CD11b, the osteoclast marker tartrate-resistant acid phosphatase, or carbonic anhydrase II. The initial loss of calcium was less in heavily calcified aortas and was associated with an increase in the Ca/P ratio from 1.49 to 1.63, consistent with a loss of nonapatitic calcium. The results indicate that vascular calcification persists after reversal of uremia, because of a lack of active resorption of apatite. This failure to resorb established calcifications may contribute to the severity of vascular calcification and suggests that therapy should be aimed at prevention.
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Affiliation(s)
- Koba A Lomashvili
- Renal Division, Emory University School of Medicine, Atlanta, Georgia
| | - Kelly E Manning
- Renal Division, Emory University School of Medicine, Atlanta, Georgia
| | - M Neale Weitzmann
- Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia
| | - Valentin Nelea
- Faculty of Dentistry, McGill University, Montréal, Québec, Canada
| | - Marc D McKee
- Faculty of Dentistry, McGill University, Montréal, Québec, Canada; Department of Anatomy and Cell Biology, McGill University, Montréal, Québec, Canada
| | - W Charles O'Neill
- Renal Division, Emory University School of Medicine, Atlanta, Georgia.
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Increased Telomere Attrition After Renal Transplantation-Impact of Antimetabolite Therapy. Transplant Direct 2016; 2:e116. [PMID: 27990481 PMCID: PMC5142370 DOI: 10.1097/txd.0000000000000629] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 09/14/2016] [Indexed: 12/13/2022] Open
Abstract
Background The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. Methods In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls. Results Non-CKD patients had significantly (P ≤ 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P = 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P = 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P < 0.0001), whereas the opposite was true for homocysteine (P < 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P = 0.003). Conclusions The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention.
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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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Bover J, Ureña-Torres P, Górriz JL, Lloret MJ, da Silva I, Ruiz-García C, Chang P, Rodríguez M, Ballarín J. Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications. Nefrologia 2016; 36:597-608. [PMID: 27595517 DOI: 10.1016/j.nefro.2016.05.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.
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Affiliation(s)
- Jordi Bover
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España.
| | - Pablo Ureña-Torres
- Departamento de Nefrología y Diálisis, Clinique du Landy, París, Francia; Departamento de Fisiología Renal, Hospital Necker, Universidad de París Descartes, París, Francia
| | - José Luis Górriz
- Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, España
| | - María Jesús Lloret
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Iara da Silva
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - César Ruiz-García
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Pamela Chang
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Mariano Rodríguez
- Servicio de Nefrología, Hospital Universitario Reina Sofía, IMIBIC, Universidad de Córdoba, Córdoba, España
| | - José Ballarín
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
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Torres A, Torregrosa V, Marcen R, Campistol JM, Arias M, Hernández D, Fernández C, Esforzado N, Paschoalin R, Pérez N, García AI, Del Amo M, Pomés J, González Rinne A, Marrero D, Pérez E, Henríquez F, Díaz JM, Silva I, López V, Perello M, Ramos D, Beneyto I, Cruzado JM, Martínez Castelao A, Bravo J, Rodríguez M, Díaz C, Crespo J, Anaya F, Rodríguez ML, Cubero JJ, Pascual P, Romero R, Andrés Belmonte A, Checa MD, Jiménez C, Escuin F, Crespo M, Mir M, Gómez G, Bayes B, González MJ, Gutiérrez A, Cuberes M, Rodríguez Benoit A, García T, Llamas F, Ortega A, Conde JL, Gómez Alamillo C. Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study). Nefrologia 2016; 36:255-67. [PMID: 27133898 DOI: 10.1016/j.nefro.2016.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 03/06/2016] [Accepted: 03/11/2016] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND AND OBJECTIVES The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.
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Affiliation(s)
- Armando Torres
- Servicio de Nefrología, HospitalUniversitario de Canarias, CIBICAN, Universidad de La Laguna, RedInRen RD12/0021/0008-Instituto de Salud Carlos III, Tenerife, Spain.
| | - Vicens Torregrosa
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Roberto Marcen
- Servicio de Nefrología, Hospital Universitario Ramón y Cajal (RedInRen, RD12/0021/0020-Instituto de Salud Carlos III), Madrid, Spain
| | - Josep María Campistol
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Manuel Arias
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, RedInRen RD12/0021/0007-Instituto de Salud Carlos III, Santander, Spain
| | - Domingo Hernández
- Servicio de Nefrología, Hospital Regional Carlos Haya, Universidad de Málaga (IBIMA), RedInRen RD12/0021/0015-Instituto de Salud Carlos III, Málaga, Spain
| | - Constantino Fernández
- Servicio de Nefrología, Complexo Hospitalario Universitario Juan Canalejo, A Coruña , Spain
| | - Nuria Esforzado
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Raphael Paschoalin
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Nuria Pérez
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Ana Isabel García
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Montserrat Del Amo
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Jaume Pomés
- Unidad de Nefrología y Trasplante Renal, Hospital Clinic, RedInRen, RD12/0021/0028, Instituto de Salud Carlos III, Barcelona, Spain
| | - Ana González Rinne
- Servicio de Nefrología, HospitalUniversitario de Canarias, CIBICAN, Universidad de La Laguna, RedInRen RD12/0021/0008-Instituto de Salud Carlos III, Tenerife, Spain
| | - Domingo Marrero
- Servicio de Nefrología, HospitalUniversitario de Canarias, CIBICAN, Universidad de La Laguna, RedInRen RD12/0021/0008-Instituto de Salud Carlos III, Tenerife, Spain
| | - Estefanía Pérez
- Servicio de Nefrología, HospitalUniversitario de Canarias, CIBICAN, Universidad de La Laguna, RedInRen RD12/0021/0008-Instituto de Salud Carlos III, Tenerife, Spain
| | - Fernando Henríquez
- Servicio de Nefrología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
| | - Juan Manuel Díaz
- Servicio de Nefrología, Fundació Puigvert I.U.N.A, Barcelona, Spain
| | - Irene Silva
- Servicio de Nefrología, Fundació Puigvert I.U.N.A, Barcelona, Spain
| | - Verónica López
- Servicio de Nefrología, Hospital Regional Carlos Haya, Universidad de Málaga (IBIMA), RedInRen RD12/0021/0015-Instituto de Salud Carlos III, Málaga, Spain
| | - Manuel Perello
- Servicio de Nefrología, Hospital Vall D́Hebrón, Barcelona, Spain
| | - David Ramos
- Servicio de Nefrología, Hospital Universitario La Fe, Valencia, Spain
| | - Isabel Beneyto
- Servicio de Nefrología, Hospital Universitario La Fe, Valencia, Spain
| | - José María Cruzado
- Servicio de Nefrología, Hospital Universitario de Bellvitge, Barcelona, Spain
| | | | - Juan Bravo
- Servicio de Nefrología, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Minerva Rodríguez
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Carmen Díaz
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Josep Crespo
- Servicio de Nefrología, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Fernando Anaya
- Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - María Luisa Rodríguez
- Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Juan José Cubero
- Servicio de Nefrología, Hospital Regional Universitario Infanta Cristina, Badajoz, Spain
| | - Pilar Pascual
- Servicio de Nefrología, Hospital Clínico Universitario de Valladolid, Spain
| | - Rafael Romero
- Servicio de Nefrología, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | | | - María Dolores Checa
- Servicio de Nefrología, Centro Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain
| | - Carlos Jiménez
- Servicio de Nefrología, Hospital Universitario La Paz, Madrid, Spain
| | - Fernando Escuin
- Servicio de Nefrología, Hospital Universitario La Paz, Madrid, Spain
| | - Marta Crespo
- Servicio de Nefrología, Hospital del Mar, Barcelona, Spain
| | - Marisa Mir
- Servicio de Nefrología, Hospital del Mar, Barcelona, Spain
| | - Gonzalo Gómez
- Servicio de Nefrología, Hospital Universitario Son Dureta, Palma de Mallorca, Spain
| | - Beatriz Bayes
- Servicio de Nefrología, Hospital Universitario Germans Trias I Pujol, Barcelona, Spain
| | - María José González
- Servicio de Nefrología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Alex Gutiérrez
- Servicio de Nefrología, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Marta Cuberes
- Servicio de Nefrología, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | | | - Teresa García
- Servicio de Nefrología, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Francisco Llamas
- Servicio de Nefrología, Complejo Hospitalario y Universitario de Albacete, Spain
| | - Agustín Ortega
- Servicio de Nefrología, Complejo Hospitalario y Universitario de Albacete, Spain
| | - José Luis Conde
- Servicio de Nefrología, Hospital Complejo Hospitario de Toledo, Spain
| | - Carlos Gómez Alamillo
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, RedInRen RD12/0021/0007-Instituto de Salud Carlos III, Santander, Spain
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Effect of Statins on the Progression of Coronary Calcification in Kidney Transplant Recipients. PLoS One 2016; 11:e0151797. [PMID: 27100788 PMCID: PMC4839705 DOI: 10.1371/journal.pone.0151797] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 02/25/2016] [Indexed: 12/26/2022] Open
Abstract
Background Coronary calcification (CAC) is highly prevalent in kidney transplant recipients (KTRs) and has been associated with cardiovascular morbidity and mortality. Some studies have shown a reduction in CAC progression with statin therapy in the general and chronic kidney disease (CKD) populations. Objectives and Methods The aim of the present study was to evaluate the effect of statins on CAC progression in incident kidney transplant recipients. Patients were randomly assigned to the statin (n = 61, 10 mg daily) and control group (n = 59). CAC and biochemical analyses were performed at baseline and 12 months. Results At baseline, CAC was observed in 30% and 21% of patients in the statin and control groups, respectively (p = 0.39). The calcium score at baseline and its absolute and relative changes over 12 months of follow up were similar among the groups. In the statin group, total cholesterol (p < 0.001), low density lipoprotein cholesterol (p < 0.001) and triglycerides (p = 0.005) decreased, and the estimated glomerular function rate increased (p<0.001) significantly. CRP levels remained stable (p = 0.52) in the statin group but increased in the control group (p = 0.01). In the multivariate model, there was no difference in CAC progression between the groups (group effect p = 0.034; time-effect p = 0.23; interaction p = 0.74). Similar results were obtained when only patients with ≥ 10AU calcium score (calcified) were analyzed (group effect p = 0.051; time-effect p = 0.58; interaction p = 0.99). Conclusion Although statins reduce the levels of cholesterol, triglycerides, inflammation and improve graft function, the dose adopted in the current study did not delay CAC progression within 12 months of follow up. Trial Registration Brazilian Clinical Trials Registry RBR-32RFMB
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