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Hamamoto FK, do Carmo Franco M, Jardim MFS, de Camargo MFC, Nogueira PCK. Cardiovascular Risk in Pediatric Renal Transplant Recipients. Pediatr Transplant 2024; 28:e14831. [PMID: 39206805 DOI: 10.1111/petr.14831] [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: 10/30/2023] [Revised: 06/28/2024] [Accepted: 07/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND The survival of pediatric chronic kidney disease (CKD) patients has improved in recent decades due to advances in dialysis and transplantation. However, cardiovascular disease (CVD) emerges as the main cause of mortality in patients with CKD. OBJECTIVES To estimate cardiovascular risk in children with CKD at least 1 year after kidney transplantation. In addition, the possible association of cardiovascular risk with classic biochemical markers and potential new markers of this outcome was investigated. METHODS An observational ambidirectional (retrospective capture of risk factors and prospective study of outcomes) research including 75 patients who underwent renal transplant between 2003 and 2013 with postoperative follow-up of at least 1 year was conducted. The outcome variables adopted were the LV mass Z-score and the presence of coronary calcification on computed tomography using calcium Agatston score. RESULT Only one patient had an elevated calcium score, and three children (4%) had an LV mass Z-score ≥ 2.0. After multivariable analysis, only gender, serum triglyceride, and serum renalase concentration remained significantly associated with LV mass. CONCLUSION The low incidence of cardiovascular changes in the population studied confirms the benefit of transplantation for the cardiovascular health of children. Nevertheless, long-term follow-up of these patients is recommended, given the limited duration of kidney function provided by transplantation and the high likelihood of further dialysis and kidney transplants being required in these children.
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Affiliation(s)
| | | | | | | | - Paulo C Koch Nogueira
- Pediatric Kidney Transplantation Department, Hospital Samaritano de São Paulo, São Paulo, Brazil
- Pediatrics Department, Federal University of São Paulo-UNIFESP, São Paulo, Brazil
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2
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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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3
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Vigil FMB, Vaz de Castro PAS, Hasparyk UG, Bartolomei VS, Simões E Silva AC. Potential Role of Bone Metabolism Markers in Kidney Transplant Recipients. Curr Med Chem 2024; 31:2809-2820. [PMID: 38332694 DOI: 10.2174/0109298673250291231121052433] [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: 03/07/2023] [Revised: 07/17/2023] [Accepted: 10/27/2023] [Indexed: 02/10/2024]
Abstract
BACKGROUND The impact of treatments, suppressing the immune system, persistent hyperparathyroidism, and other risk factors on mineral and bone disorder (MBD) after kidney transplantation is well-known. However, there is limited knowledge about their effect on bone metabolism biomarkers. This study aimed to investigate the influence of kidney transplant on these markers, comparing them to patients undergoing hemodialysis and healthy individuals. METHODS In this cross-sectional study, three groups were included: kidney transplant patients (n = 57), hemodialysis patients (n = 26), and healthy controls (n = 31). Plasma concentrations of various bone metabolism biomarkers, including Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23, were measured. Associations between these biomarkers and clinical and laboratory data were evaluated. RESULTS A total of 114 patients participated. Transplant recipients had significantly lower levels of Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23 compared to hemodialysis patients. Alkaline phosphatase levels positively correlated with osteopontin (r = 0.572, p < 0.001), while fibroblast growth factor 23 negatively correlated with 25-hydroxyvitamin D (r = -0.531, p = 0.019). The panel of bone biomarkers successfully predicted hypercalcemia (area under the curve [AUC] = 0.852, 95% confidence interval [CI] = 0.679-1.000) and dyslipidemia (AUC = 0.811, 95% CI 0.640-0.982) in transplant recipients. CONCLUSION Kidney transplantation significantly improves mineral and bone disorders associated with end-stage kidney disease by modulating MBD markers and reducing bone metabolism markers, such as Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, and sclerostin. Moreover, the panel of bone biomarkers effectively predicted hypercalcemia and dyslipidemia in transplant recipients.
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Affiliation(s)
- Flávia Maria Borges Vigil
- Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
- Hospital Evangélico, Belo Horizonte, MG, Brazil
| | - Pedro Alves Soares Vaz de Castro
- Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Ursula Gramiscelli Hasparyk
- Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Victória Soares Bartolomei
- Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Ana Cristina Simões E Silva
- Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
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4
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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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5
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Seyahi N, Alagoz S, Atli Z, Ozcan SG, Tripepi G, Bakir A, Trabulus S, Pekmezci S, Zoccali C. Coronary artery calcification progression and long-term cardiovascular outcomes in renal transplant recipients: an analysis by the joint model. Clin Kidney J 2022; 15:101-108. [PMID: 35106150 PMCID: PMC8796795 DOI: 10.1093/ckj/sfab174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/23/2021] [Indexed: 01/07/2023] Open
Abstract
Background Compared with the general population, the risk of death is substantially higher in renal transplant recipients than in age- and sex-matched individuals in the general population. In the general population, coronary artery calcification (CAC) predicts all-cause and cardiovascular mortality. In this study we aimed to analyse these relationships in renal transplant recipients. Methods We examined 178 renal transplant patients in this prospective observational cohort study. We measured CAC with multidetector spiral computed tomography using the Agatston score at multiple time points. Overall, 411 scans were performed in 178 patients over an average 12.8 years follow-up. The clinical endpoint was a composite including all-cause death and non-fatal cardiovascular events. Data analysis was performed by the joint model. Results During a follow-up of 12.8 ± 2.4 years, coronary calcification progressed over time (P < 0.001) and the clinical endpoint occurred in 54 patients. In the analysis by the joint model, both the baseline CAC score and the CAC score progression were strongly associated with the incidence rate of the composite event [hazard ratio 1.261 (95% confidence interval 1.119–1.420), P = 0.0001]. Conclusions CAC at baseline and coronary calcification progression robustly predict the risk of death and cardiovascular events in renal transplant recipients. These findings support the hypothesis that the link between the calcifying arteriopathy of renal transplant patients and clinical end points in these patients is causal in nature.
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Affiliation(s)
- Nurhan Seyahi
- Department of Internal Medicine, Division of Nephrology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
| | - Selma Alagoz
- Department of Nephrology, Health Sciences University, Istanbul Training and Research Hospital, Istanbul, Turkey
| | - Zeynep Atli
- Department of Account and Tax Application, Sinop University, Sinop, Turkey
| | - Seyda Gul Ozcan
- Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Giovanni Tripepi
- Institute of Clinical Epidemiology, Clinical Epidemiology and Physiopathology of Renal Diseases, Hypertension of Reggio Calabria, Reggio Calabria, Italy
| | - Alev Bakir
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Halic University, Istanbul, Turkey
| | - Sinan Trabulus
- Department of Internal Medicine, Division of Nephrology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
| | - Salih Pekmezci
- Department of General Surgery, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Carmine Zoccali
- Associazione Ipertensione, Nefrologia, Trapianto Renale c/o Nephrology and Renal Transplantation Division Ospedali Riuniti, Reggio Calabria, Italy
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6
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Kumar R, Anandh U, Ramesh G. Lessons learnt from progressive vascular calcification in a renal transplant recipient. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_48_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Ueki K, Tsuchimoto A, Matsukuma Y, Nakagawa K, Tsujikawa H, Masutani K, Tanaka S, Kaku K, Noguchi H, Okabe Y, Unagami K, Kakuta Y, Okumi M, Nakamura M, Tsuruya K, Nakano T, Tanabe K, Kitazono T. Development and validation of a risk score for the prediction of cardiovascular disease in living donor kidney transplant recipients. Nephrol Dial Transplant 2021; 36:365-374. [PMID: 33367750 DOI: 10.1093/ndt/gfaa275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 09/04/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening. METHODS A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital. RESULTS In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity. CONCLUSIONS The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations.
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Affiliation(s)
- Kenji Ueki
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Yuta Matsukuma
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Kaneyasu Nakagawa
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Hiroaki Tsujikawa
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Kosuke Masutani
- Department of Internal Medicine, Faculty of Medicine, Division of Nephrology and Rheumatology, Fukuoka University, Fukuoka, Japan
| | - Shigeru Tanaka
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Keizo Kaku
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Noguchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kohei Unagami
- Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoichi Kakuta
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masayoshi Okumi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
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8
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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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9
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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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10
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Chinnappa S, El Nahas M, Mooney A. Reversal of asymptomatic cardiac dysfunction following renal transplantation. Clin Kidney J 2020; 14:720-722. [PMID: 33841851 PMCID: PMC8023313 DOI: 10.1093/ckj/sfaa010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 01/07/2020] [Indexed: 11/12/2022] Open
Affiliation(s)
- Shanmugakumar Chinnappa
- Department of Nephrology, Doncaster and Bassetlaw Teaching Hospitals, Doncaster, UK.,Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Meguid El Nahas
- Department of Nephrology, University of Sheffield, Sheffield, UK
| | - Andrew Mooney
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.,Department of Nephrology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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11
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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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12
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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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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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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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Parajuli S, Clark DF, Djamali A. Is Kidney Transplantation a Better State of CKD? Impact on Diagnosis and Management. Adv Chronic Kidney Dis 2016; 23:287-294. [PMID: 27742382 DOI: 10.1053/j.ackd.2016.09.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Patients with CKD are at increased risk for cardiovascular events, hospitalizations, and mortality. Kidney transplantation (KTx) is the preferred treatment for end-stage kidney disease. Although comorbidities including anemia and bone and mineral disease improve or are even halted after KTx, kidney transplant recipients carry higher cardiovascular mortality risk than the general population, as well as an increased risk of infections, malignancies, fractures, and obesity. When comparing CKD with CKD after transplantation (CKD-T), the rate of decline of estimated glomerular filtration rate (eGFR) is significantly lower in CKD-T. Higher rate of decline of eGFR has been associated with increased risk of mortality. However, due to the significant increased risk of mortality due to cardiovascular events, infections, and malignancies, many kidney transplant recipients may not benefit of decline in the rate of eGFR. Patients with CKD-T are a unique subset of patients with multiple traditional and transplant-specific risk factors. Proper management and appropriate preventive health measures may improve long-term patient and allograft survival in patients with CKD-T.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Dana F Clark
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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16
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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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Markossian T, Burge N, Ling B, Schneider J, Pacold I, Bansal V, Leehey D, Stroupe K, Chang A, Kramer H. Controversies Regarding Lipid Management and Statin Use for Cardiovascular Risk Reduction in Patients With CKD. Am J Kidney Dis 2016; 67:965-77. [PMID: 26943983 DOI: 10.1053/j.ajkd.2015.12.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 12/07/2015] [Indexed: 11/11/2022]
Abstract
Adults with chronic kidney disease (CKD) are at heightened risk for dying of cardiovascular disease. Results from randomized clinical trials of statin drugs versus placebo demonstrate that statin drugs or statin plus ezetimibe reduce the absolute risk for coronary heart disease and mortality among adults with non-dialysis-dependent CKD. The Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline for lipid management in CKD recommends that adults 50 years or older with non-dialysis-dependent CKD be treated with a statin or statin plus ezetimibe regardless of low-density lipoprotein cholesterol levels. However, at least 9 guidelines published during the last 5 years address lipid management for primary and secondary prevention of atherosclerotic cardiovascular disease, and not all guidelines address the utility of lipid-lowering therapy in adults with CKD. Because most patients with CKD receive most of their clinical care from non-nephrologists, differences in recommendations for lipid-lowering therapy for cardiovascular disease prevention may negatively affect the clinical care of adults with CKD and cause confusion for both patients and providers. This review addresses the identification and management of lipid levels in patients with CKD and discusses the existing controversies regarding testing and treatment of lipid levels in the CKD population.
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Affiliation(s)
- Talar Markossian
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | | | - Benjamin Ling
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | - Julia Schneider
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | - Ivan Pacold
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | - Vinod Bansal
- Department of Medicine, Loyola University Chicago, Maywood, IL
| | - David Leehey
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | - Kevin Stroupe
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL
| | - Alex Chang
- Department of Medicine, Geisinger Medical Center, Danville, PA
| | - Holly Kramer
- Hines Veterans Administration Hospital, Hines, IL; Department of Medicine, Loyola University Chicago, Maywood, IL.
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18
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Clinical imaging of vascular disease in chronic kidney disease. Int Urol Nephrol 2016; 48:827-37. [PMID: 26898824 DOI: 10.1007/s11255-016-1240-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 02/05/2016] [Indexed: 12/18/2022]
Abstract
Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.
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Egido J, Martínez-Castelao A, Bover J, Praga M, Torregrosa JV, Fernández-Giráldez E, Solozábal C. Efectos pleiotrópicos del paricalcitol, más allá del metabolismo óseo-mineral. Nefrologia 2016; 36:10-8. [DOI: 10.1016/j.nefro.2015.11.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 10/30/2015] [Indexed: 12/20/2022] Open
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D’Marco L, Bellasi A, Mazzaferro S, Raggi P. Vascular calcification, bone and mineral metabolism after kidney transplantation. World J Transplant 2015; 5:222-230. [PMID: 26722649 PMCID: PMC4689932 DOI: 10.5500/wjt.v5.i4.222] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Revised: 09/01/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article.
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Alagoz S, Cebi D, Akman C, Altiparmak MR, Serdengecti K, Seyahi N. Progression of coronary artery calcification in living kidney donors: a follow-up study. Nephron Clin Pract 2014; 126:144-50. [PMID: 24776642 DOI: 10.1159/000362169] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Accepted: 03/06/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Data on the long-term mortality and morbidity of living kidney donors are scarce. In the general population, coronary artery calcification (CAC) and progression of CAC are predictors of future cardiac risk. We conducted a study to determine the progression of CAC in renal transplant donors. METHODS We used multidetector computed tomography to examine CAC in 75 former renal transplant donors. A baseline and a follow-up scan were performed and changes in CAC scores were evaluated in each subject individually to calculate the incidence of CAC progression. RESULTS Baseline CAC prevalence was 16% and the mean CAC score was 5.3 ± 25.8. At the follow-up scan that was performed after an average of 4.8 ± 0.3 years, CAC prevalence increased to 72% and the mean CAC score to 12.5 ± 23.4. Progression of the individual CAC score was found between 18.7 and 26.7%, depending on the method used to define progression. In patients with baseline CAC, the mean annualized rate of CAC progression was 2.1. Presence of hypertension, high systolic blood pressure and an increase in BMI were the determinants of CAC progression. CONCLUSIONS The rate of CAC progression does not seem to be high in carefully selected donors.
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Affiliation(s)
- Selma Alagoz
- Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
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22
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Vipattawat K, Kitiyakara C, Phakdeekitcharoen B, Kantachuvesiri S, Sumethkul V, Jirasiritham S, Stitchantrakul W, Disthabanchong S. Vascular calcification in long-term kidney transplantation. Nephrology (Carlton) 2014; 19:251-256. [PMID: 24447254 DOI: 10.1111/nep.12210] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2014] [Indexed: 02/05/2023]
Abstract
AIM Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.
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Affiliation(s)
- Kotcharat Vipattawat
- Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Alendronate as an effective treatment for bone loss and vascular calcification in kidney transplant recipients. J Transplant 2014; 2014:269613. [PMID: 24696777 PMCID: PMC3945217 DOI: 10.1155/2014/269613] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 01/15/2014] [Indexed: 12/19/2022] Open
Abstract
Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC) is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects) and a control group (group C: 7 subjects). Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1) the time-dependent change in bone mineral density (BMD) estimated with DEXA and (2) progression of abdominal AC, calculated twice as an index (ACI) using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% (P = 0.015 versus baseline), and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%), but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%, P = 0.061). In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR.
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Abstract
The epidemic of obesity and metabolic syndrome (MS) contributes to the rapid growth of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is a reverse epidemiology, known as the "obesity paradox," in ESRD patients receiving maintenance dialysis. Obese patients are routinely referred for kidney transplant, and they have more surgical and medical complications than non-obese patients. However, compared to dialysis, kidney transplant provides a survival benefit for obese patients. After kidney transplant, obese patients tend to gain more body weight, and non-obese patients can develop new-onset obesity/MS. Obesity/MS is not only associated with serious morbidities, but also compromises the long-term graft and patient survival. The immunosuppressive drugs commonly used as maintenance therapy, including corticosteroids, calcineurin inhibitors and mammalian target-of-rapamycin inhibitors, contribute to obesity/MS. Development of novel immunosuppressive drugs free of metabolic adverse effects is needed, so that the full potential and benefits of kidney transplantation can be realized.
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Calcium and osteoprotegerin levels predict the progression of the abdominal aortic calcifications after kidney transplantation. Transplantation 2013; 96:42-8. [PMID: 23812001 PMCID: PMC3713767 DOI: 10.1097/tp.0b013e3182934cee] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background Vascular calcifications (VCs) are a cardiovascular risk factor in patients affected by chronic kidney disease and after kidney transplantation (KTx). We evaluated the prevalence of VCs at the abdominal aortic site in KTx patients at the time of transplantation and 1 year after KTx, exploring the possibly associated factors. Methods In 107 transplanted patients, the following parameters were evaluated at the first and twelfth month after KTx: the aortic calcification index (ACI), fibroblast growth factor 23, osteoprotegerin (OPG), fetuin A, and clinical and biochemical parameters. Patients were followed up for 2 years after KTx. Results At the time of KTx, 60% of patients had some degree of VC (ACI>0), whereas 40% had no VC. One year after KTx, VCs worsened in 26% of patients, whereas in 74%, VCs remained stable or improved. The progression of VC was observed almost exclusively in patients with a positive ACI score at the first month. At the multivariate analysis, serum calcium, OPG, and estimated glomerular filtration rate were the only variables independently associated with the progression of VC. Conclusions VCs at the aortic site are frequent in KTx patients, and in a significant percentage of them, they tend to progress even in the short time. High levels of serum calcium and OPG are significantly associated with the progression of VCs. Whether these associations are based on a cause-effect relationship and their correction might impact on the calcification process could be ascertained by prospective interventional studies.
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Recovery versus persistence of disordered mineral metabolism in kidney transplant recipients. Semin Nephrol 2013; 33:191-203. [PMID: 23465505 DOI: 10.1016/j.semnephrol.2012.12.019] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In patients with end-stage renal disease, successful renal transplantation improves the quality of life and increases survival, as compared with long-term dialysis treatment. Although it long has been believed that successful kidney transplantation to a large extent solves the problem of chronic kidney disease-mineral and bone disorders (CKD-MBD), increasing evidence indicates that it only changes the phenotype of CKD-MBD. Posttransplant CKD-MBD reflects the effects of immunosuppression, previous CKD-MBD persisting after transplantation, and de novo CKD-MBD. A major and often-underestimated problem after successful renal transplantation is persistent hyperparathyroidism. Besides contributing to posttransplant hypercalcemia and hypophosphatemia, persistent hyperparathyroidism may be involved in the pathogenesis of allograft dysfunction (nephrocalcinosis), progression of vascular calcification, and bone disease (uncoupling of bone formation and bone resorption and bone mineral density loss) in renal transplant recipients. Similar to nontransplanted patients, CKD-MBD has a detrimental impact on (cardiovascular) mortality and morbidity. Additional studies urgently are needed to get more insights into the pathophysiology of posttransplant CKD-MBD. These new insights will allow for a more targeted and causal therapeutic approach.
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27
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Disthabanchong S. Lowering vascular calcification burden in chronic kidney disease: Is it possible? World J Nephrol 2013; 2:49-55. [PMID: 24255887 PMCID: PMC3832912 DOI: 10.5527/wjn.v2.i3.49] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 05/21/2013] [Accepted: 07/18/2013] [Indexed: 02/06/2023] Open
Abstract
High prevalence of atherosclerosis and arterial calcification in chronic kidney disease is far beyond the explanation by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcification. Strategies to lower vascular calcification burden in chronic kidney disease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate binders, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on efficacy and patient outcomes are necessary. Several large randomized controlled trials have confirmed the lack of benefit of statin in attenuating the progression of vascular calcification.
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28
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The European Renal Best Practice (ERBP) Transplantation guideline development group, Abramowicz D, Cochat P, Claas F, Dudley C, Harden P, Heeman U, Hourmant M, Maggiore U, Pascual J, Salvadori M, Spasovski G, Squifflet JP, Steiger J, Torres A, Vanholder R, Van Biesen W, Viklicky O, Zeier M, Nagler E. ERBP Guideline on the Management and Evaluation of the Kidney Donor and Recipient. Nephrol Dial Transplant 2013; 28 Suppl 2:ii1-ii71. [PMID: 24026881 DOI: 10.1093/ndt/gft218] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Adamidis KN, Pleros C, Oikonomaki T, Kyratzi I, Exarchos D, Metaxatos G, Drakopoulos S, Nikolopoulou N, Apostolou T. Progression of coronary artery calcification after kidney transplantation. Ren Fail 2013; 35:1075-8. [PMID: 23879313 DOI: 10.3109/0886022x.2013.815090] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Calcification of coronary vessels progresses rapidly in hemodialysis (HD) patients and comprises a strong predictor of cardiovascular events. The aim of this prospective study was to evaluate the coronary artery calcification (CAC) in patients with end stage renal disease undergoing regular HD and to determine the effect of renal transplantation (RT) in the progression of CAC, using the Agatston technique for calcium scoring. The study included 20 patients with end-stage renal disease undergoing a regular HD treatment (16 males, 4 females) 54.1 ± 9.5 years old who had just received a renal transplant and 16 more HD patients (11 males, 5 females) 54.4 ± 13.8 years old as control group. The baseline evaluation showed a very high prevalence of CAC in both groups, which was positively correlated with age (p < 0.001) and CRP (p = 0.03). The second (follow-up) evaluation showed a significant slower progression of calcification after RT. In both groups, high calcium score values in the follow-up evaluation had a strong positive correlation with baseline calcium score (p < 0.001).
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Alshayeb HM, Josephson MA, Sprague SM. CKD-mineral and bone disorder management in kidney transplant recipients. Am J Kidney Dis 2012; 61:310-25. [PMID: 23102732 DOI: 10.1053/j.ajkd.2012.07.022] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Accepted: 07/09/2012] [Indexed: 12/11/2022]
Abstract
Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23-parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease.
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Affiliation(s)
- Hala M Alshayeb
- Department of Medicine, Section of Nephrology, University of Chicago, Chicago, IL, USA
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Seyahi N, Cebi D, Altiparmak MR, Akman C, Ataman R, Pekmezci S, Serdengecti K. Progression of coronary artery calcification in renal transplant recipients. Nephrol Dial Transplant 2011; 27:2101-7. [PMID: 21965591 DOI: 10.1093/ndt/gfr558] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Cardiovascular disease is the leading cause of mortality among renal transplant recipients. In the general population, coronary artery calcification (CAC) and progression of CAC are predictors of future cardiac risk. We conducted a study to determine the progression of CAC in renal transplant recipients; we also examined the factors associated with progression and the impact of the analytic methods used to determine CAC progression. METHODS We used multi-detector computed tomography to examine CAC in 150 prevalent renal transplant recipients, who did not have a documented cardiovascular disease. A baseline and a follow-up scan were performed and changes in CAC scores were evaluated in each patient individually, to calculate the incidence of CAC progression. Multivariate logistic regression analysis was used to evaluate the determinants of CAC progression. RESULTS Baseline CAC prevalence was 35.3% and the mean CAC score was 60.0 ± 174.8. At follow-up scan that was performed after an average of 2.8 ± 0.4 years, CAC prevalence increased to 64.6% and the mean CAC score to 94.9 ± 245.7. Progression of individual CAC score was found between 28.0 and 38.0%, depending on the method used to define progression. In patients with baseline CAC, median annualized rate of CAC progression was 11.1. Baseline CAC, high triglyceride and bisphosphonate use were the independent determinants of CAC progression. CONCLUSIONS Renal transplantation does not stop or reverse CAC. Progression of CAC is the usual evolution pattern of CAC in renal transplant recipients. Beside baseline CAC, high triglyceride level and bisphosphonate use were associated with progression of CAC.
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Affiliation(s)
- Nurhan Seyahi
- Department of Internal Medicine, Division of Nephrology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
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Maréchal C, Coche E, Goffin E, Dragean A, Schlieper G, Nguyen P, Floege J, Kanaan N, Devuyst O, Jadoul M. Progression of coronary artery calcification and thoracic aorta calcification in kidney transplant recipients. Am J Kidney Dis 2011; 59:258-69. [PMID: 21944666 DOI: 10.1053/j.ajkd.2011.07.019] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Accepted: 07/22/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN Longitudinal. SETTING & PARTICIPANTS The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES & MEASUREMENTS The Agatston score was measured again 3.5 or more years later. RESULTS Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.
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Affiliation(s)
- Céline Maréchal
- Division of Nephrology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium
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Copley JB, Wüthrich RP. Therapeutic management of post-kidney transplant hyperparathyroidism. Clin Transplant 2011; 25:24-39. [PMID: 20572835 DOI: 10.1111/j.1399-0012.2010.01287.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Left uncontrolled, persistent post-kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre-existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long-term uncontrolled HPT in post-kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy-associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post-kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non-surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post-kidney transplant HPT, associated complications, and current options for clinical management.
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Maréchal C, Schlieper G, Nguyen P, Krüger T, Coche E, Robert A, Floege J, Goffin E, Jadoul M, Devuyst O. Serum fetuin-A levels are associated with vascular calcifications and predict cardiovascular events in renal transplant recipients. Clin J Am Soc Nephrol 2011; 6:974-85. [PMID: 21527649 DOI: 10.2215/cjn.06150710] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up. RESULTS Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio=1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene. CONCLUSIONS These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.
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Affiliation(s)
- Céline Maréchal
- Division of Nephrology, Cliniques Universitaires Saint-Luc, UCL Medical School, 10 Avenue Hippocrate, B-1200 Brussels, Belgium
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Mathews SJ, de las Fuentes L, Podaralla P, Cabellon A, Zheng S, Bierhals A, Spence K, Slatopolsky E, Davila-Roman VG, Delmez JA. Effects of sodium thiosulfate on vascular calcification in end-stage renal disease: a pilot study of feasibility, safety and efficacy. Am J Nephrol 2011; 33:131-8. [PMID: 21242673 PMCID: PMC3064860 DOI: 10.1159/000323550] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2010] [Accepted: 12/12/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients. METHODS Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density. RESULTS Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta. CONCLUSION STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.
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Affiliation(s)
- Santhosh Jay Mathews
- Cardiovascular Imaging and Clinical Research Core Laboratory and Cardiovascular Division, Washington University School of Medicine, St. Louis, Mo., USA
| | - Lisa de las Fuentes
- Cardiovascular Imaging and Clinical Research Core Laboratory and Cardiovascular Division, Washington University School of Medicine, St. Louis, Mo., USA
| | - Prashanth Podaralla
- Division of Nephrology, Washington University School of Medicine, St. Louis, Mo., USA
| | - Anton Cabellon
- Division of Nephrology, Washington University School of Medicine, St. Louis, Mo., USA
| | - Sijie Zheng
- Division of Nephrology, Washington University School of Medicine, St. Louis, Mo., USA
| | - Andrew Bierhals
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Mo., USA
| | - Karen Spence
- Cardiovascular Imaging and Clinical Research Core Laboratory and Cardiovascular Division, Washington University School of Medicine, St. Louis, Mo., USA
| | - Eduardo Slatopolsky
- Division of Nephrology, Washington University School of Medicine, St. Louis, Mo., USA
| | - Victor G. Davila-Roman
- Cardiovascular Imaging and Clinical Research Core Laboratory and Cardiovascular Division, Washington University School of Medicine, St. Louis, Mo., USA
| | - James A. Delmez
- Division of Nephrology, Washington University School of Medicine, St. Louis, Mo., USA
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Seyahi N, Kahveci A, Cebi D, Altiparmak MR, Akman C, Uslu I, Ataman R, Tasci H, Serdengecti K. Coronary artery calcification and coronary ischaemia in renal transplant recipients. Nephrol Dial Transplant 2010; 26:720-6. [PMID: 20621931 DOI: 10.1093/ndt/gfq413] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cardiovascular disease is the leading cause of mortality among renal transplant recipients. Data on the relationship between coronary artery calcification (CAC) and coronary ischaemia in renal transplantation patients are scant. We conducted a study to determine the prevalence and determinants of CAC in these patients; we also examined the frequency of coronary ischaemia in patients with moderate and severe CAC. METHODS We used multi-detector spiral computed tomography to examine CAC in 178 consecutive renal transplant recipients. Angina pectoris was sought with the Rose questionnaire. The extent of calcification was measured by Agatston score. Myocardial perfusion scintigraphy was performed in patients with moderate and severe CAC. Multivariate logistic and linear regression analysis was used to evaluate the determinants of CAC presence and CAC score, respectively. RESULTS CAC was present in 72 patients (40.4%), mean CAC score was 113.7±275.5 (median: 0 and range: 0-1712). Age, time on transplantation and Rose angina pectoris were the independent determinants of both CAC presence and high CAC scores in all multivariate models. Coronary ischaemia was detected in 17.1% of the patients with moderate-to-severe CAC. CONCLUSIONS CAC is highly prevalent in renal transplant recipients; it is associated with symptoms of coronary ischaemia. Time on transplantation is an independent determinant of CAC. Future studies to evaluate the prognostic significance of CAC in these patients are necessary.
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Affiliation(s)
- Nurhan Seyahi
- Department of Internal Medicine, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey.
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Bargnoux AS, Dupuy AM, Garrigue V, Jaussent I, Gahide G, Badiou S, Szwarc I, Deleuze S, Vernhet H, Cristol JP, Mourad G. Evolution of coronary artery calcifications following kidney transplantation: relationship with osteoprotegerin levels. Am J Transplant 2009; 9:2571-9. [PMID: 19775319 DOI: 10.1111/j.1600-6143.2009.02814.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV >or= 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395-5652] to 527 [217-1818] pg/mL and parathyroid hormone from 94 [1-550] to 62 [16-410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02-8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456-3285]) vs. non-progressors (899 [396-5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.
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Affiliation(s)
- A-S Bargnoux
- Department of Biochemistry, University of Montpellier, Montpellier, France
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Civilibal M, Caliskan S, Kurugoglu S, Candan C, Canpolat N, Sever L, Kasapcopur O, Arisoy N. Progression of coronary calcification in pediatric chronic kidney disease stage 5. Pediatr Nephrol 2009; 24:555-563. [PMID: 18982357 DOI: 10.1007/s00467-008-1038-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2008] [Revised: 09/30/2008] [Accepted: 10/06/2008] [Indexed: 02/06/2023]
Abstract
Coronary artery calcification (CAC) is common in adults with chronic kidney disease (CKD) and progresses with time. However, data are limited for younger patients. We have previously reported CAC in eight of 53 children with CKD. After 2 years, CAC evaluation was repeated in 48 patients. The median CAC score (CACS) increased from 101.3 (1473.6 +/- 1978.6, range 8.5-4332) to 1759.2 (2236.4 +/- 2463.3, range 0-5858) Agatston units (AU). When the individual changes in CACS were evaluated one by one, we showed a mild decrease in two patients on hemodialysis (HD) and in one transplant (Tx) recipient, a moderate increase in one patient on HD, one on peritoneal dialysis (PD) and one Tx recipient, and a large increase in one HD patient. Also, CAC disappeared in one HD patient. All patients with no calcification at baseline remained calcification-free at follow-up. To obtain the individual cumulative exposure, we calculated time-averaged mean values, using the laboratory values from the beginning of dialysis to the first and second multidetector spiral computed tomography (MDCT) scans (baseline and final values, respectively). Final CACS was positively related to final calcium-phosphorus (CaxP) product, while CAC progression was inversely associated with final serum albumin level. This report is the first study with the largest number and the youngest cohort to document the natural history of coronary calcification.
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Affiliation(s)
- Mahmut Civilibal
- Department of Pediatric Nephrology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey.
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Mazzaferro S, Pasquali M, Taggi F, Baldinelli M, Conte C, Muci ML, Pirozzi N, Carbone I, Francone M, Pugliese F. Progression of coronary artery calcification in renal transplantation and the role of secondary hyperparathyroidism and inflammation. Clin J Am Soc Nephrol 2009; 4:685-90. [PMID: 19211668 DOI: 10.2215/cjn.03930808] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Transplantation should favorably affect coronary calcification (CAC) progression in dialysis; however, changes in CAC score in the individual patient are not reliably evaluated. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS The authors used special tables of reproducibility limits for each score level to study, by multislice computed tomography and biochemistries, the 2-year changes in CAC in 41 transplant patients (age 48 +/- 13 yr, 25 men, dialysis vintage 4.8 +/- 4.3 yr, underwent transplant 6.2 +/- 5.5 yr prior). Thirty balanced dialysis patients served as controls. RESULTS In the study group, Agatston score was stable, and C-reactive protein decreased, whereas fetuin and osteoprotegerin increased. In the control group, Agatston score increased, parathyroid hormone and phosphate decreased, and inflammation markers were persistently twice as high as in the study group. With regard to individual changes, 12.2% transplant patients worsened, compared with 56.6% of patients in dialysis (P < 0.0001). Patients without calcification at entry showed slower progression in transplantation (8.3%) than in dialysis (44.4%; P < 0.034), and the difference was similar to that observed in cases with CAC (17.6% versus 61.9%; P < 0.007). Discriminant analysis indicated parathyroid hormone, the modality of therapy (dialysis or transplantation), and erythrocyte sedimentation rate as the variables most associated with worsening. CONCLUSIONS Renal transplantation lowers but does not halt CAC progression. Inflammation and hyperparathyroidism are associated with progression in the populations studied.
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Affiliation(s)
- Sandro Mazzaferro
- Department of Clinical Science, University of Rome La Sapienza, Rome, Italy.
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40
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Cinacalcet Increases Calcium Excretion in Hypercalcemic Hyperparathyroidism After Kidney Transplantation. Transplantation 2008; 86:919-24. [DOI: 10.1097/tp.0b013e318186b7fb] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Adeseun GA, Rivera ME, Thota S, Joffe M, Rosas SE. Metabolic syndrome and coronary artery calcification in renal transplant recipients. Transplantation 2008; 86:728-32. [PMID: 18791455 PMCID: PMC2656432 DOI: 10.1097/tp.0b013e3181826d12] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Coronary artery calcification (CAC) and metabolic syndrome (MS) have been associated with increased cardiovascular risk. The study objective was to examine the association of MS with CAC presence and progression in renal transplant recipients. METHODS We measured the CAC progression in asymptomatic recipients who had no prior history of coronary artery disease. RESULTS MS was common (55.4%). Median CAC scores were 0, 33.1, 98, and 261.9 for patients with one, two, three, and four or more positive components of the MS, respectively. Severe CAC scores were more common in recipients with MS (P=0.04). Although recipients with MS had higher mean CAC scores at baseline and significant CAC progression (483 [590.6] vs. 619 [813.8], P=0.01), MS was not an independent predictor of annualized rate of CAC change in a multivariate model. CONCLUSION Future studies to evaluate if MS treatment improves cardiovascular outcomes are imperative.
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Affiliation(s)
- Gbemisola A. Adeseun
- Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Maria E. Rivera
- Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Subhashini Thota
- Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Marshall Joffe
- Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sylvia E. Rosas
- Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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42
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Surana SP, Keithi-Reddy SR, Singh AK. Diffuse vascular calcification in a dialysis patient. Kidney Int 2008; 73:890-4. [PMID: 18185505 DOI: 10.1038/sj.ki.5002770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- S P Surana
- Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Sprague SM, Belozeroff V, Danese MD, Martin LP, Olgaard K. Abnormal bone and mineral metabolism in kidney transplant patients--a review. Am J Nephrol 2007; 28:246-53. [PMID: 17989497 DOI: 10.1159/000110875] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2007] [Accepted: 09/10/2007] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Abnormal bone and mineral metabolism is common in patients with kidney failure and often persists after successful kidney transplant. METHODS To better understand the natural history of this disease in transplant patients, we reviewed the literature by searching MEDLINE for English language articles published between January 1990 and October 2006 that contained Medical Subject Headings and key words related to secondary or persistent hyperparathyroidism and kidney transplant. RESULTS Parathyroid hormone levels decreased significantly during the first 3 months after transplant but typically stabilized at elevated values after 1 year. Calcium tended to increase after transplant and then stabilize at the higher end of the normal range within 2 months. Phosphorus decreased rapidly to within or below normal levels after surgery and hypophosphatemia, if present, resolved within 2 months. Low levels of 1,25(OH)2 vitamin D typically did not reach normal values until almost 18 months after transplant. CONCLUSION This review provides evidence demonstrating that abnormal bone and mineral metabolism exists in patients after kidney transplant and suggests the need for treatment of this condition. However, better observational and interventional research is needed before advocating such a treatment guideline.
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Affiliation(s)
- Stuart M Sprague
- Evanston Northwestern Healthcare, Northwestern University Feinberg School of Medicine, Evanston, Ill. 60201, USA.
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44
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Current World Literature. Curr Opin Nephrol Hypertens 2007; 16:388-93. [PMID: 17565283 DOI: 10.1097/mnh.0b013e3282472fd5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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45
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Covic A, Gusbeth-Tatomir P, Goldsmith DJA. VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: Vascular Calcification-A New Window on the Cardiovascular System: Role of Agents Used to Manipulate Skeletal Integrity. Semin Dial 2007; 20:158-69. [PMID: 17374091 DOI: 10.1111/j.1525-139x.2007.00265.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Adrian Covic
- Nephrology Clinic, "Dr. C. I. Parhon" University Hospital, Iasi, Romania.
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46
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Mazzaferro S, Pasquali M, Pugliese F, Barresi G, Carbone I, Francone M, Sardella D, Taggi F. Serum levels of calcification inhibition proteins and coronary artery calcium score: comparison between transplantation and dialysis. Am J Nephrol 2007; 27:75-83. [PMID: 17259697 DOI: 10.1159/000099095] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2006] [Accepted: 12/21/2006] [Indexed: 01/07/2023]
Abstract
Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 +/- 12 years; 30 males, 21 females; previous D duration 4.8 +/- 4.2 years; Tx since 6.6 +/- 5.5 years; Cr 1.8 +/- 0.6 mg/dl) and in 49 D patients (age 49 +/- 14 years; 30 males,19 females; D duration 5.6 +/- 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 +/- 1,637 vs. 1,311 +/- 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: r(s) = 0.439, p < 0.001, and r(s) = 0.510, p < 0.0001; D: r(s) = 0.471, p < 0.001, and r(s) = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (r(s) = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (r(s) = -0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (r(m) = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (r(m) = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.
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Affiliation(s)
- Sandro Mazzaferro
- Division of Nephrology, Department of Clinical Science, University of Rome La Sapienza, Rome, Italy.
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