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An overview of the mechanisms in vascular calcification during chronic kidney disease.
Voelkl, J, Cejka, D, Alesutan, I
Current opinion in nephrology and hypertension. 2019;(4):289-296
Abstract
PURPOSE OF REVIEW Chronic kidney disease (CKD) facilitates a unique environment to strongly accelerate vascular calcification - the pathological deposition of calcium-phosphate in the vasculature. These calcifications are associated with the excessive cardiovascular mortality of CKD patients. RECENT FINDINGS Vascular calcification is a multifaceted active process, mediated, at least partly, by vascular smooth muscle cells. These cells are able to transdifferentiate into cells with osteo/chondrogenic properties, which exert multiple effects to facilitate vascular tissue mineralization. As the understanding of the underlying pathophysiology increases, first therapeutic concepts begin to emerge. SUMMARY This brief review provides an overview on the so far known mechanisms involved in the initiation and progression of vascular calcification in CKD.
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Creatine is a Conditionally Essential Nutrient in Chronic Kidney Disease: A Hypothesis and Narrative Literature Review.
Post, A, Tsikas, D, Bakker, SJL
Nutrients. 2019;(5)
Abstract
To accommodate the loss of the plethora of functions of the kidneys, patients with chronic kidney disease require many dietary adjustments, including restrictions on the intake of protein, phosphorus, sodium and potassium. Plant-based foods are increasingly recommended as these foods contain smaller amounts of saturated fatty acids, protein and absorbable phosphorus than meat, generate less acid and are rich in fibers, polyunsaturated fatty acids, magnesium and potassium. Unfortunately, these dietary recommendations cannot prevent the occurrence of many symptoms, which typically include fatigue, impaired cognition, myalgia, muscle weakness, and muscle wasting. One threat coming with the recommendation of low-protein diets in patients with non-dialysis-dependent chronic kidney disease (CKD) and with high-protein diets in patients with dialysis-dependent CKD, particularly with current recommendations towards proteins coming from plant-based sources, is that of creatine deficiency. Creatine is an essential contributor in cellular energy homeostasis, yet on a daily basis 1.6-1.7% of the total creatine pool is degraded. As the average omnivorous diet cannot fully compensate for these losses, the endogenous synthesis of creatine is required for continuous replenishment. Endogenous creatine synthesis involves two enzymatic steps, of which the first step is a metabolic function of the kidney facilitated by the enzyme arginine:glycine amidinotransferase (AGAT). Recent findings strongly suggest that the capacity of renal AGAT, and thus endogenous creatine production, progressively decreases with the increasing degree of CKD, to become absent or virtually absent in dialysis patients. We hypothesize that with increasing degree of CKD, creatine coming from meat and dairy in food increasingly becomes an essential nutrient. This phenomenon will likely be present in patients with CKD stages 3, 4 and 5, but will likely be most pronouncedly present in patients with dialysis-dependent CKD, because of the combination of lowest endogenous production of creatine and unopposed losses of creatine into the dialysate. It is likely that these increased demands for dietary creatine are not sufficiently met. The result of which, may be a creatine deficiency with important contributions to the sarcopenia, fatigue, impaired quality of life, impaired cognition, and premature mortality seen in CKD.
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3.
[Antifibrotic renal role of mineralcorticoid receptor antagonists].
Ocello, A, La Rosa, S, Fiorini, F, Randone, S, Maccarrone, R, Battaglia, G, Granata, A
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 2019;(4)
Abstract
Cardiovascular and renal diseases are one of the main health problems in all industrialized countries. Their incidence is constantly increasing due to the aging of the population and the greater prevalence of obesity and type 2 diabetes. Clinical evidence suggests that aldosterone and the activation of mineralocorticoid receptors (MR) have a role in the pathophysiology of cardiovascular and renal diseases. Moreover, clinical studies demonstrate the benefits of mineralocorticoid receptor antagonists (MRAs) on mortality and progression of heart and kidney disease. In addition to renal effects on body fluid homeostasis, aldosterone has multiple extrarenal effects including the induction of inflammation, vascular rigidity, collagen formation and stimulation of fibrosis. Given the fundamental role of MR activation in renal and cardiac fibrosis, effective and selective blocking of the signal with MRAs can be used in the clinical practice to prevent or slow down the progression of heart and kidney diseases. The aim of the present work is to review the role of MRAs in light of the new evidence as well as its potential use as an antifibrotic in chronic kidney disease (CKD). The initial clinical results suggest that MRAs are potentially useful in treating patients with chronic kidney disease, particularly in cases of diabetic nephropathy. We don't yet have efficacy and safety data on the progression of kidney disease up to the end stage (ESRD) and filling this gap represents an important target for future trials.
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4.
Engaging people with chronic kidney disease in their own care an integrative review.
Almeida, OAE, Santos, WS, Rehem, TCMSB, Medeiros, M
Ciencia & saude coletiva. 2019;(5):1689-1698
Abstract
The treatment of chronic kidney disease (CKD) places a major burden on patients and their families. Interventions such as nutritional management, medication regimen, and renal replacement therapies require active patient participation. An integrative literature review was carried out to identify articles on the engagement and participation of people with CKD in their care. The Medical Subject Headings (MeSH) "Kidney Failure, Chronic", "Self Care", and "Patient Participation" were used to conduct a search on the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), the U.S. National Library of Medicine® (Medline/PubMed), Biblioteca Virtual em Saúde (Bireme). A total of 21 articles published between 2012 and 2016 were selected. The most commonly used data collection and analysis techniques were semi-structured interviews and phenomenological thematic analysis, respectively. The articles were categorized into the following thematic groups: illness management and treatment; involvement in the decision-making process; advanced care plan; and home peritoneal dialysis. We found that there is a lack of qualitative research in certain areas, namely kidney transplant recipients and people with initial stages of CKD. People with CKD should be encouraged to actively engage in their own care, which in turn requires the knowledge, motivation and support of health professionals.
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Crosstalk between fibroblast growth factor 23, iron, erythropoietin, and inflammation in kidney disease.
Babitt, JL, Sitara, D
Current opinion in nephrology and hypertension. 2019;(4):304-310
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Abstract
PURPOSE OF REVIEW Recent research has revealed that regulation of the bone-secreted hormone fibroblast growth factor 23 (FGF23) is not limited to classical mineral factors. Specifically, bidirectional relationships have been described between FGF23 production and anemia, iron status, and inflammation. Here, we will review the latest published articles on the crosstalk between FGF23 and the aforementioned nonclassical factors. RECENT FINDINGS It has been recently reported that erythropoietin, iron deficiency, and inflammation increase FGF23 production and metabolism. Moreover, FGF23 promotes anemia and regulates inflammatory responses. These findings are particularly important in the setting of chronic kidney disease which is characterized by elevated FGF23 levels and several associated comorbidities. SUMMARY Regulation of FGF23 is complex and involves many bone and renal factors. More recently, erythropoietin, iron deficiency, and inflammation have been also shown to affect FGF23 transcription and cleavage. Importantly, FGF23 has emerged as a regulator of erythropoiesis, iron metabolism, and inflammation. These findings provide novel and important insights into the pathophysiologic mechanisms of chronic kidney disease and may present new opportunities for therapeutic clinical interventions.
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Advances in management of chronic metabolic acidosis in chronic kidney disease.
Chen, W, Abramowitz, MK
Current opinion in nephrology and hypertension. 2019;(5):409-416
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Abstract
PURPOSE OF REVIEW Chronic metabolic acidosis is a common complication of chronic kidney disease (CKD) and is associated with adverse consequences, such as CKD progression and muscle wasting. We review the findings from recent clinical trials that have examined the effects of sodium bicarbonate therapy and veverimer in patients with CKD and chronic metabolic acidosis. RECENT FINDINGS There are four recent clinical trials on chronic metabolic acidosis of CKD. In a pilot, cross-over study, 6 weeks of sodium bicarbonate therapy improved vascular endothelial function, measured by brachial artery flow-mediated dilation. In a single-center, randomized, open-label study, 6 months of sodium bicarbonate therapy increased muscle mass and lean body mass, and preserved kidney function. The other two clinical trials (phase 1/2 and phase 3 studies) examined the effects of veverimer, which is a hydrochloric acid binder. The phase 3 study showed that 12-weeks of veverimer increased serum bicarbonate levels and might improve physical function. The effects of veverimer on CKD progression, physical function and cardiovascular endpoints as well as its long-term safety are yet to be determined. SUMMARY Recent studies suggest that sodium bicarbonate therapy may improve vascular endothelial function and muscle mass, and preserve renal function. Veverimer increases serum bicarbonate level and could be a potential new therapeutic option for treating chronic metabolic acidosis.
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How Low Do We Go (in the Post-SPRINT Era)?
Burgner, A, Lewis, JB
Advances in chronic kidney disease. 2019;(2):110-116
Abstract
Hypertension is frequently both a cause and complication of CKD. The optimal blood pressure target in CKD has been of hot debate over the decades with little data to inform the goals. Here, we review the data from the Systolic Blood Pressure Intervention Trial (SPRINT), Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), Ramipril Efficacy in Nephropathy-2 (REIN-2), and Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials to use the available evidence to better inform what blood pressure goal should be recommended in patients with CKD and to answer the question "How low should we go?".
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Dietary Components That May Influence the Disturbed Gut Microbiota in Chronic Kidney Disease.
Mafra, D, Borges, N, Alvarenga, L, Esgalhado, M, Cardozo, L, Lindholm, B, Stenvinkel, P
Nutrients. 2019;(3)
Abstract
Gut microbiota imbalance is common in patients with chronic kidney disease (CKD) and associates with factors such as increased circulating levels of gut-derived uremic toxins, inflammation, and oxidative stress, which are linked to cardiovascular disease and increased morbimortality. Different nutritional strategies have been proposed to modulate gut microbiota, and could potentially be used to reduce dysbiosis in CKD. Nutrients like proteins, fibers, probiotics, and synbiotics are important determinants of the composition of gut microbiota and specific bioactive compounds such as polyphenols present in nuts, berries. and fruits, and curcumin, may also play a key role in this regard. However, so far, there are few studies on dietary components influencing the gut microbiota in CKD, and it is therefore not possible to conclude which nutrients should be prioritized in the diet of patients with CKD. In this review, we discuss some nutrients, diet patterns and bioactive compounds that may be involved in the modulation of gut microbiota in CKD and provide the background and rationale for studies exploring whether nutritional interventions with these dietary components could be used to alleviate the gut dysbiosis in patients with CKD.
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Anticoagulation in Patients With Advanced Chronic Kidney Disease: Walking the Fine Line Between Benefit and Harm.
Jegatheswaran, J, Hundemer, GL, Massicotte-Azarniouch, D, Sood, MM
The Canadian journal of cardiology. 2019;(9):1241-1255
Abstract
Chronic kidney disease affects more than 3 million Canadians and is highly associated with cardiovascular diseases that require anticoagulation, such as atrial fibrillation and venous thromboembolism. Patients with chronic kidney disease are at a problematic crossroads; they are at high risk of thrombotic conditions requiring anticoagulation and bleeding complications due to anticoagulation. The limited high-quality clinical evidence to guide decision-making in this area further compounds the dilemma. In this review, we discuss the physiology and epidemiology of bleeding and thrombosis in patients with kidney disease. We specifically focus on patients with advanced kidney disease (estimated glomerular filtration rate ≤ 30 mL/min) or who are receiving dialysis and focus on the nephrologist perspective regarding these issues. We summarize the existing evidence for anticoagulation use in the prevention of stroke with atrial fibrillation and provide practical clinical recommendations for considering anticoagulation use in this population. Last, we examine specific scenarios such as the use of a glomerular filtration rate estimating equation and dosing, the use of existing prediction tools for stroke and hemorrhage risk, current patterns of anticoagulation use (including during the dialysis procedure), and vascular calcification with vitamin K antagonist use in patients with chronic kidney disease.
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Chronic kidney disease of unknown aetiology in Sri Lanka and the exposure to environmental chemicals: a review of literature.
Kulathunga, MRDL, Ayanka Wijayawardena, MA, Naidu, R, Wijeratne, AW
Environmental geochemistry and health. 2019;(5):2329-2338
Abstract
Chronic kidney disease of unknown aetiology (CKDu) has emerged as a serious health issue in Sri Lanka. The disease has been recorded in the North Central Province of the country. While studies have elicited many hypotheses concerning the pathogenicity of CKDu, none adequately explains the cause of CKDu and the measures needed to minimise its occurrence. Nephrotoxic heavy metal (oid)s such as cadmium, arsenic, lead, and chromium are present in biological samples of people from endemic areas. This review appraises evidence on the effects of long-term exposure to low concentration of nephrotoxic heavy metals, which could be the principal cause of CKDu. Although a considerable variation exists in metal concentrations in patients' blood and urine, higher levels of heavy metals were consistently observed in affected areas. This review finds that the populations in the endemic areas are exposed to heavy metal (oid)s at low concentrations, which are considered as safe levels; nevertheless, it influences the incidence of CKDu. Recent global studies on chronic kidney disease (CKD) revealed a low concentration of heavy metals in diseased patients. Research findings indicated that CKDu patients in Sri Lanka demonstrated similar blood levels of Cd, Pb, and higher concentrations of Cr than that have been reported globally. Further studies on the influence of combinations of nephrotoxic heavy metals at low concentrations on reduced glomerular filtration rate and other renal biomarkers could explain CKDu pathogenicity.