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“ Kidney Failure is good at ….calcifying things!"
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Cozzolino, M., et al. (2023). "Future treatment of vascular calcification in chronic kidney disease." Expert Opinion on Pharmacotherapy 24(18): 2041-2057 https://doi.org/10.1080/14656566.2023.2266381 ARTICLE REQUEST FORM
Cardiovascular disease (CVD) is one of the global leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Vascular calcification (VC) is a major cause of CVD in this population and is the consequence of complex interactions between inhibitor and promoter factors leading to pathological deposition of calcium and phosphate in soft tissues. Different pathological landscapes are associated with the development of VC, such as endothelial dysfunction, oxidative stress, chronic inflammation, loss of mineralization inhibitors, release of calcifying extracellular vesicles (cEVs) and circulating calcifying cells. In this review, we examined the literature and summarized the pathophysiology, biomarkers and focused on the treatments of VC. Even though there is no consensus regarding specific treatment options, we provide the currently available treatment strategies that focus on phosphate balance, correction of vitamin D and vitamin K deficiencies, avoidance of both extremes of bone turnover, normalizing calcium levels and reduction of inflammatory response and the potential and promising therapeutic approaches liketargeting cellular mechanisms of calcification (e.g. SNF472, TNAP inhibitors). Creating novel scores to detect in advance VC and implementing targeted therapies is crucial to treat them and improve the future management of these patients.
Izzo, C., et al. (2024). "Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview." Life 14(3): 418 https://www.mdpi.com/2075-1729/14/3/418 PDF @ Link
Chronic kidney disease (CKD) is a global health issue with a rising prevalence, affecting 697.5 million people worldwide. It imposes a substantial burden, contributing to 35.8 million disability-adjusted life years (DALYs) and 1.2 million deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 and 2017, positioning it as a significant cause of global mortality. CKD is associated with diverse health complications, impacting cardiovascular, neurological, nutritional, and endocrine aspects. One prominent complication is CKD–mineral and bone disorder (MBD), a complex condition involving dysregulation of bone turnover, mineralization, and strength, accompanied by soft tissue and vascular calcification. Alterations in mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and Klotho, play pivotal roles in CKD-MBD. These disturbances, observed early in CKD, contribute to the progression of bone disorders and renal osteodystrophy (ROD). Vascular calcification (VC) is a key component of CKD-MBD, accelerated by CKD. The pathophysiology involves complex processes in vascular smooth muscle cells and the formation of calciprotein particles (CPP). VC is closely linked to cardiovascular events and mortality, emphasizing its prognostic significance. Various serum markers and imaging techniques, including lateral plain X-ray, Kauppila Score, Adragao Score, and pulse wave velocity, aid in VC detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. CKD poses a substantial global health burden, and its complications, including CKD-MBD and VC, significantly contribute to morbidity and mortality. Understanding the intricate relationships between mineral metabolism, bone disorders, and vascular calcification is crucial for effective diagnosis and therapeutic interventions.
Jansz, T. T., et al. (2021). "Coronary Artery Calcification as a Marker for Coronary Artery Stenosis: Comparing Kidney Failure to the General Population." Kidney Medicine 3(3): 386-394.e381 https://www.sciencedirect.com/science/article/pii/S2590059521000662
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Rationale & Objective The presence of calcified plaques in the coronary arteries is associated with cardiovascular mortality and is a hallmark of chronic kidney failure, but it is unclear whether this is associated with the same degree of coronary artery stenosis as in patients without kidney disease. We compared the relationship of coronary artery calcification (CAC) and stenosis between dialysis patients and patients without chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 127 dialysis patients and 447 patients without CKD with cardiovascular risk factors underwent cardiac computed tomography (CT), consisting of non–contrast-enhanced CT and CT angiography. CAC score and degree of coronary artery stenosis were assessed by independent readers. Predictor Dialysis treatment. Outcome Association between calcification and stenosis. Analytical Approach Logistic regression to determine the association between CAC score and the presence of stenosis in a matched cohort and, in the full cohort, testing for the interaction of dialysis status with this relationship. Results 112 patients were matched from each cohort, totaling 224 patients, using propensity scores for dialysis, balancing numerous cardiovascular risk factors. Median CAC score was 210 (IQR, 19-859) in dialysis patients and 58 (IQR, 0-254) in patients without CKD; 35% of dialysis patients and 36% of patients without CKD had coronary artery stenosis≥50%. Per each 100-unit higher CAC score, the matched dialysis cohort had significantly lower ORs for stenosis than the non-CKD cohort, 0.67 (95% CI, 0.52-0.83) for stenosis≥50% and 0.75 (95% CI, 0.62-0.90) for stenosis≥70%. Limitations No comparison with the gold standard fractional flow reserve. Conclusions Dialysis patients have higher risk for coronary artery stenosis with higher CAC scores, but this risk is comparatively lower than in patients without CKD with similar CAC scores. In dialysis patients, a high CAC score can easily be found without significant stenosis. Our data enable “translation” of degree of calcification to the probability of coronary stenosis in dialysis patients.
Kanbay, M., et al. (2023). "The pathophysiology and management of vascular calcification in chronic kidney disease patients." Expert Review of Cardiovascular Therapy 21(2): 75-85 https://doi.org/10.1080/14779072.2023.2174525 ARTICLE REQUEST FORM
Vascular calcification (VC) which is the pathological mineral deposition in the vascular system, predominantly at the intimal and medial layer of the vessel wall, is an important comorbidity in patients with chronic kidney disease (CKD) leading to significant morbidity and mortality while necessitating appropriate treatment. Our review aims to provide an in-depth analysis of the current understanding of VC. In this review, we first discuss the pathophysiology of VC in CKD patients, then we explain the methods to predict and assess VC. Afterwards, we provide the currently available as well as the potential therapeutic approaches of VC. We finally discuss our understanding regarding the current situation surrounding VC in our expert opinion section. Predicting, assessing and treating VC is crucial and the future advances in the field of research surrounding VC will potentially occur in one or more of these three areas of clinical management. There is a current lack of evidence and consensus regarding specific therapeutic options for alleviating VC and this situation may not necessitate VC to be determined, detected, and documented before the available options are implemented. Regardless, the prediction and assessment of VC is still important and requires further improvement together with the developments in therapeutic alternatives. The future has the potential to bring better research which would guide and improve the management of this patient group. A more specialized approach consisting of targeted therapies and more tailored management plans for patients with CKD and VC is on the horizon.
Kim, J. S. and H. S. Hwang (2021). "Vascular Calcification in Chronic Kidney Disease: Distinct Features of Pathogenesis and Clinical Implication." kcj 51(12): 961-982 http://dx.doi.org/10.4070/kcj.2021.0995 PDF @ Link
Author's summary: Vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD) and leads to increased cardiovascular morbidity and mortality. In patients with CKD, traditional factors do not fully explain the high prevalence of VC. This suggests that a CKD-specific pathobiology is involved in the development of VC and mounting evidence indicates that VC in CKD patients has distinct features of clinical presentation and that clinical implications are changed compared to those in the general population. In this review, we discuss the mechanism, diagnostic imaging modalities, clinical features and implications, and management of VC in patients with CKD.
Ward, L. J., et al. (2023). "Coronary artery calcification and aortic valve calcification in patients with kidney failure: a sex-disaggregated study." Biology of Sex Differences 14(1): 48 https://doi.org/10.1186/s13293-023-00530-x PDF @ Link
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF.
Zhang, J., et al. (2023). "Associated factors of cardiac valve calcification and its prognostic effects among patients with chronic kidney disease: a systematic review and meta-analysis." Frontiers in Cardiovascular Medicine Volume 10 - 2023 https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1120634 PDF @ Link
Background: Cardiac valve calcification (CVC) is highly prevalent and a risk factor for adverse outcomes in patients with chronic kidney disease (CKD). This meta-analysis aimed to investigate the risk factors for CVC and association between CVC and mortality in CKD patients. Method: Three electronic databases including PubMed, Embase, and Web of Science were searched for relevant studies up to November 2022. Hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (CI) were pooled using random-effect meta-analyses. Results: 22 studies were included in the meta-analysis. Pooled analyses showed that CKD patients with CVC were relatively older, had a higher body mass index, left atrial dimension, C-reaction protein level, and a declined ejection fraction. Calcium and phosphate metabolism dysfunction, diabetes, coronary heart disease, and duration of dialysis were all predictors for CVC in CKD patients. The presence of CVC (both aortic valve and mitral valve) increased the risk of all-cause and cardiovascular mortality in CKD patients. However, the prognostic value of CVC for mortality was not significant anymore in patients with peritoneal dialysis. Conclusion: CKD patients with CVC had a greater risk of all-cause and cardiovascular mortality. Multiple associated factors for development of CVC in CKD patients should be taken into consideration by healthcare professionals to improve prognosis.
Henrich's Principles and Practice of Dialysis
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Nephrology
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Oxford Handbook of Dialysis
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Handbook of Dialysis Therapy
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Dialysis in Older Adults
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