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The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts.
Viegas, C, Araújo, N, Marreiros, C, Simes, D
Aging. 2019;(12):4274-4299
Abstract
Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.
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Leveraging the coronary calcium scan beyond the coronary calcium score.
Bos, D, Leening, MJG
European radiology. 2018;(7):3082-3087
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UNLABELLED Non-contrast cardiac computed tomography in order to obtain the coronary artery calcium score has become an established diagnostic procedure in the clinical setting, and is commonly employed in clinical and population-based research. This state-of-the-art review paper highlights the potential gain in information that can be obtained from the non-contrast coronary calcium scans without any necessary modifications to the scan protocol. This includes markers of cardio-metabolic health, such as the amount of epicardial fat and liver fat, but also markers of general health including bone density and lung density. Finally, this paper addresses the importance of incidental findings and of radiation exposure accompanying imaging with non-contrast cardiac computed tomography. Despite the fact that coronary calcium scan protocols have been optimized for the visualization of coronary calcification in terms image quality and radiation exposure, it is important for radiologists, cardiologists and medical specialists in the field of preventive medicine to acknowledge that numerous additional markers of cardio-metabolic health and general health can be readily identified on a coronary calcium scan. KEY POINTS • The coronary artery calcium score substantially increased the use of cardiac CT. • Cardio-metabolic and general health markers may be derived without changes to the scan protocol. • Those include epicardial fat, aortic valve calcifications, liver fat, bone density, and lung density. • Clinicians must be aware of this potential additional yield from non-contrast cardiac CT.
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[Symmetrical and bilateral basal ganglia calcification. Case series and literature review].
Jiménez-Ruiz, A, Cárdenas-Sáenz, O, Ruiz-Sandoval, JL
Gaceta medica de Mexico. 2018;(2):258-262
Abstract
INTRODUCTION Symmetric, bilateral basal ganglia calcification is rare finding that sometimes occurs asymptomatically. Its prevalence increases with age, and the most affected site is the globus pallidus. REPORT OF CASES A series of seven cases with clinical and imaging diagnosis of basal ganglia calcification, recorded during the 2012 to 2016 period at the Department of Internal Medicine of the Hospital Civil de Guadalajara "Fray Antonio Alcalde, is presented. Most common clinical presentation was with altered alertness, headache and seizures. There was one case with movement disorders; there were no cases identified with dementia or tetany. CONCLUSION Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment.
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Calcification of the heart: mechanisms and therapeutic avenues.
Shekar, C, Budoff, M
Expert review of cardiovascular therapy. 2018;(7):527-536
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Coronary artery calcification (CAC) is reflective of atherosclerotic disease and incrementally predictive of future cardiovascular events (CVE), independent of traditional risk factors. Extra coronary calcium such as aortic valve calcification, which can be identified and quantified by computed tomography (CT) imaging, has shown to predict future CVE in both asymptomatic and symptomatic (i.e. stable angina and acute coronary syndrome [ACS]) settings. It has hence been a vital tool in studies involving new therapies for cardiovascular disease. Areas covered: In this review, promising therapies on the horizon are reviewed, along with the role of cardiac CT and coronary calcification in these studies. A Medline search for peer-reviewed publications using keywords related to coronary calcium score, aortic valve calcium, and therapies targeting the same was carried out. Expert commentary: CT scanning provides a distinct means of detecting and quantifying coronary plaque as well as valvular calcification with excellent reproducibility. Based on voluminous data available, the absence of coronary calcium serves as a factor to de-risk patients for cardiovascular risk stratification and management algorithms. Newer therapies have shown to lower progression of coronary calcification, thus being beneficial in slowing progression of atherosclerotic disease. As British Epidemiologist Geoffrey Rose states, the best predictor of a life-threatening disease is the early manifestation of that disease. As CAC represents the early manifestation of atherosclerosis, it is the best-known stratifier of risk today, and its clinical use will continue to rise.
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Treatment of Pediatric Chronic Kidney Disease-Mineral and Bone Disorder.
Hanudel, MR, Salusky, IB
Current osteoporosis reports. 2017;(3):198-206
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PURPOSE OF REVIEW In this paper, we review the pathogenesis and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD), especially as it relates to pediatric CKD patients. RECENT FINDINGS Disordered regulation of bone and mineral metabolism in CKD may result in fractures, skeletal deformities, and poor growth, which is especially relevant for pediatric CKD patients. Moreover, CKD-MBD may result in extra-skeletal calcification and cardiovascular morbidity. Early increases in fibroblast growth factor 23 (FGF23) levels play a key, primary role in CKD-MBD pathogenesis. Therapeutic approaches in pediatric CKD-MBD aim to minimize complications to the growing skeleton and prevent extra-skeletal calcifications, mainly by addressing hyperphosphatemia and secondary hyperparathyroidism. Ongoing clinical trials are focused on assessing the benefit of FGF23 reduction in CKD. CKD-MBD is a systemic disorder that has significant clinical implications. Treatment of CKD-MBD in children requires special consideration in order to maximize growth, optimize skeletal health, and prevent cardiovascular disease.
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Extracorporeal shock wave therapy, ultrasound-guided percutaneous lavage, corticosteroid injection and combined treatment for the treatment of rotator cuff calcific tendinopathy: a network meta-analysis of RCTs.
Arirachakaran, A, Boonard, M, Yamaphai, S, Prommahachai, A, Kesprayura, S, Kongtharvonskul, J
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2017;(3):381-390
Abstract
Treatment of calcific tendinitis using extracorporeal shock wave therapy (ESWT), ultrasound-guided percutaneous lavage (UGPL or barbotage), subacromial corticosteroid injection (SAI) and combined treatment is still controversial. This systematic review and meta-regression aimed to compare clinical outcomes between treatments. Relevant RCTs were identified using PubMed and Scopus search engines to date of September 23, 2015. Seven of 920 studies identified were eligible. Compared to the other treatments, the results of this study indicate that ESWT significantly improved CMS and VAS when compared to placebo. Barbotage plus ESWT significantly improved CMS, VAS and decreased size of calcium deposit when compared to ESWT, while barbotage plus SAI significantly improved CMS and decreased size of calcium deposit when compared to SAI. There have no different adverse effects of all treatment groups. Multiple active treatment comparisons indicated that barbotage plus SAI significantly improved VAS and size of calcium deposit when compared to other groups, while barbotage plus SAI improved CMS when compared to other groups. But there was no significant difference. The network meta-analysis suggested that combined US-guided needling and subacromial corticosteroid injection significantly decreased shoulder pain VAS, improved CMS score and decreased the size of calcium deposits, while also lowering risks of adverse event when compared to barbotage plus ESWT, ESWT and subacromial corticosteroid injection; therefore, the evidence points to UGPL as being the treatment of choice for nonsurgical options of treatment in calcific tendinitis of the shoulder. Level of evidence I.
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Pulmonary Alveolar Microlithiasis - Clinico-Radiological dissociation - A case report with Radiological review.
Khaladkar, SM, Kondapavuluri, SK, Kamal, A, Kalra, R, Kuber, R
Journal of radiology case reports. 2016;(1):14-21
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare chronic lung disease characterized by deposition of intra alveolar calcium and phosphate in bilateral lung parenchyma with predominance in lower and mid zones. Etiology and pathogenesis is not fully understood. However, mutation in SLC34A2 gene that encodes a sodium phosphate co-transporter in alveolar type-II cells resulting in formation and accumulation of microliths rich in calcium phosphate due to impaired clearance is considered the cause of disease. Patients with PAM are asymptomatic till development of hypoxemia and cor pulmonale. It remains static, while in some it progresses to pulmonary fibrosis, respiratory failure and cor pulmonale. We report a case of 44 year old male patient presenting with progressive shortness of breath on exertion for one year in duration with dry cough, more since last six months. Chest radiograph showed dense micronodular opacities giving classical sandstorm appearance. High resolution computed tomography (HRCT) showed microcalcification, subpleural cystic changes and calcified pleura. Lung biopsy showed calcospherites within alveolar spaces.
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Novel assessments of systemic calcification propensity.
Pasch, A
Current opinion in nephrology and hypertension. 2016;(4):278-84
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PURPOSE OF REVIEW Blood is a biological fluid, which controls the precipitation of calcium and phosphate and transports mineral debris. This review presents and discusses the current concepts and novel assessment methods of systemic calcification propensity in blood. RECENT FINDINGS Calcium and phosphate combine with calcification-inhibiting proteins, mainly fetuin-A, to form amorphous calcium phosphate-containing primary calciprotein particles (CPPs). These nanosized mineral-protein clusters undergo spontaneous transformation to secondary CPP, which contain crystalline calcium phosphate. Two recently developed methods assess complementary aspects of the calcification propensity of serum. The CPP-fetuin-A method determines the amount of sedimentable fetuin-A, whereas the T50-Test determines the transformation time point T50 from amorphous to crystalline CPPs in artificially supersaturated serum.Clinical studies in renal patients have already demonstrated close associations of the CPP-fetuin-A method with all-cause mortality, severity of coronary calcification and aortic stiffness, and of the T50-Test with cardiovascular and all-cause mortality, renal graft failure and aortic stiffening. SUMMARY Systemic calcification propensity can be assessed by two novel methods providing complementary information about the status and performance of the humoral calcification-regulating system in serum. These tests may help guide better patient care in the future with the use of more individualized therapies.
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Balloon expandable transcatheter heart valves for native mitral valve disease with severe mitral annular calcification.
Guerrero, M, Urena, M, Pursnani, A, Wang, DD, Vahanian, A, O'Neill, W, Feldman, T, Himbert, D
The Journal of cardiovascular surgery. 2016;(3):401-9
Abstract
Patients with mitral annular calcification (MAC) have high surgical risk for mitral valve replacement due to associated comorbidities and technical challenges related to calcium burden, precluding surgery in many patients. Transcatheter mitral valve replacement (TMVR) with the compassionate use of balloon expandable aortic transcatheter heart valves has been used in this clinical scenario. The purpose of this review was to summarize the early experience including successes and failures reported. TMVR might evolve into an acceptable alternative for selected patients with severe MAC who are not candidates for conventional mitral valve surgery. However, this field is at a very early stage and the progress will be significantly slower than the development of transcatheter aortic valve replacement due to the complexity of the mitral valve anatomy and its pathology. Optimizing patient selection process by using multimodality imaging tools to accurately measure the mitral valve annulus and evaluate the risk of left ventricular outflow tract obstruction is essential to minimize complications. Strategies for treating and preventing left ventricular outflow tract obstruction are being tested. Similarly, carefully selecting candidates avoiding patients at the end of their disease process, might improve the overall outcomes.
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Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD.
Colbert, G, Jain, N, de Lemos, JA, Hedayati, SS
Clinical journal of the American Society of Nephrology : CJASN. 2015;(3):515-29
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Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.