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1.
Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: a systematic review and meta-analysis.
Smyth, LJ, Cañadas-Garre, M, Cappa, RC, Maxwell, AP, McKnight, AJ
BMJ open. 2019;(4):e026777
Abstract
BACKGROUND Chronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and prevalence rates of CKD are increasing. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance through the kidney. RAAS activation is associated with hypertension, which is directly implicated in causation and progression of CKD. RAAS blockade, using drugs targeting individual RAAS mediators and receptors, has proven to be renoprotective. OBJECTIVES To assess genomic variants present within RAAS genes, ACE, ACE2, AGT, AGTR1, AGTR2 and REN, for association with CKD. DESIGN AND DATA SOURCES A systematic review and meta-analysis of observational research was performed to evaluate the RAAS gene polymorphisms in CKD using both PubMed and Web of Science databases with publication date between the inception of each database and 31 December 2018. Eligible articles included case-control studies of a defined kidney disease and included genotype counts. ELIGIBILITY CRITERIA Any paper was removed from the analysis if it was not written in English or Spanish, was a non-human study, was a paediatric study, was not a case-control study, did not have a renal disease phenotype, did not include data for the genes, was a gene expression-based study or had a pharmaceutical drug focus. RESULTS A total of 3531 studies were identified, 114 of which met the inclusion criteria. Genetic variants reported in at least three independent publications for populations with the same ethnicity were determined and quantitative analyses performed. Three variants returned significant results in populations with different ethnicities at p<0.05: ACE insertion, AGT rs699-T allele and AGTR1 rs5186-A allele; each variant was associated with a reduced risk of CKD development. CONCLUSIONS Further biological pathway and functional analyses of the RAAS gene polymorphisms will help define how variation in components of the RAAS pathway contributes to CKD.
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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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3.
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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[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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Thermal disinfection in hemodialysis using the A0 concept as dispenser.
Toapanta Gaibor, NG, Gil Sacaluga, L, de la Cerda Ojeda, F, Molas Cotén, JR, Salgueira Lazo, M
Nefrologia. 2019;(5):482-488
Abstract
Patients with chronic kidney disease in the hemodialysis program are exposed to large amounts of water, as this constitutes about 96% of the dialysis fluid. It is known that the use of better quality water decreases the state of chronic inflammation in dialysis patients. Disinfection as part of water treatment plays an important role in meeting the established quality standards; currently, heat disinfection is highly recommended, however its dose is not clearly established in the literature. The objective of this review is to know what is available in the literature on the dose of heat disinfection that should be used in hemodialysis and to present our experience with this method at a set dose of 12.000 A0.
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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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Recovery Of Bone And Muscle Mass In Patients With Chronic Kidney Disease And Iron Overload On Hemodialysis And Taking Combined Supplementation With Curcumin And Resveratrol.
Murillo Ortiz, BO, Fuentes Preciado, AR, Ramírez Emiliano, J, Martínez Garza, S, Ramos Rodríguez, E, de Alba Macías, LA
Clinical interventions in aging. 2019;:2055-2062
Abstract
INTRODUCTION Malnutrition is common in haemodialysis patients and closely related to morbidity and mortality. We evaluated the effect of twelve weeks of supplementation with resveratrol and curcumin on recovery of bone and muscle mass and protein oxidation, lipid peroxidation on patients with chronic kidney disease and iron overload undergoing hemodialysis, we performed a randomized, double-blind, placebo-controlled trial. METHODS We included a total of 40 patients, were randomly assigned to two groups, 20 to the group with antioxidant supplementation (Resveratrol + Curcumin) (Group A), treated with a daily oral dose of 500 mg of Resveratrol and 500 mg of Curcumin, and 20 to the control group treated with placebo (Group B). RESULTS Significant differences were found in the body composition of the patients between both groups. There was a significant difference in Body Mass Index (BMI) values (p = 0.002), fat percentage (p = 0.007), muscle mass (p = 0.01) bone mass (p = 0.01), as well as in the score of the subjective global evaluation (p = 0.03). Also differences were found between the basal and final serum levels of Triglycerides (TG) (p = 0.01), VLDL (p = 0.003). A significant decrease in the levels of serum ferritin (2003.69 ± 518.73 vs 1795.65 ± 519.00 ng/mL; p = 0.04). Nor were significant differences observed between the baseline and the final Thiobarbituric Acid Reactive Substances (TBARS) values (70.45 ± 69.21 vs 50.19 ± 32.62, p = 0.24). The same results was obtained for carbonyl values (2.67 ± 0.75 vs 2.50 ± 0.85; p = 0.50). DISCUSSION The present study is the first assay on patients with chronic kidney disease and iron overload that demonstrates the beneficial effects of combined supplementation with Curcumin and Resveratrol on muscle and bone mass. There was a significant decrease in circulating levels of ferritin, to finding that remarkably novel.
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Oral anticoagulation in patients with chronic kidney disease: A systematic review and meta-analysis.
Malhotra, K, Ishfaq, MF, Goyal, N, Katsanos, AH, Parissis, J, Alexandrov, AW, Alexandrov, AV, Tsivgoulis, G
Neurology. 2019;(21):e2421-e2431
Abstract
OBJECTIVE Data regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce. METHODS Systematic review and meta-analysis of studies involving patients with CKD treated with oral anticoagulants were conducted to evaluate the following outcomes: ischemic stroke, intracerebral hemorrhage (ICH), combined ischemic and hemorrhagic stroke (strokecombined), stroke or systemic embolism, mortality, and major bleeding events. CKD was defined based on creatinine clearance (CrCl) ranging from mild (CrCl: 60-89 mL/min), moderate (CrCl: 30-59 mL/min), to severe (CrCl: 15-29 mL/min). RESULTS Fifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55-0.84]) and mortality (RR = 0.70; 95% CI 0.62-0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33-0.56), strokecombined (RR = 0.83; 95% CI 0.72-0.96), stroke or systemic embolism (RR = 0.73; 95% CI 0.62-0.85), and major bleeding (RR = 0.77; 95% CI 0.66-0.90). In adjusted analyses, warfarin use (vs no anticoagulant) was associated with reduced mortality (HRadj = 0.68; 95% CI 0.61-0.76), whereas NOAC (vs warfarin) use reduced the risk of ICH (HRadj = 0.39; 95% CI 0.30-0.50) and stroke or systemic embolism (HRadj = 0.75; 95% CI 0.65-0.88). Our sensitivity analyses comparing different NOACs exhibited that factor Xa inhibitors (compared to warfarin) consistently reduced strokecombined (RR = 0.84; 95% CI 0.73-0.96), mortality (RR = 0.84; 95% CI 0.70-1.00), ICH (RR = 0.45; 95% CI 0.24-0.85), and major bleeding (RR = 0.76; 95% CI 0.64-0.91). CONCLUSIONS Among patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.
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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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The Role of Saline and Sodium Bicarbonate Preprocedural Hydration to Prevent Mid-term Renal Insufficiency in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.
Hagikura, A, Goto, K, Takebayashi, H, Kikuta, Y, Kobayashi, K, Sato, K, Taniguchi, M, Hiramatsu, S, Kawai, Y, Kohno, H, et al
Internal medicine (Tokyo, Japan). 2019;(8):1057-1065
Abstract
Objective Persistent renal damage (RD) three months after exposure to contrast media is associated with contrast-induced acute kidney injury (CI-AKI) and poor clinical outcomes. Little is known about the role of preprocedural hydration on persistent RD in patients with chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] undergoing percutaneous coronary intervention (PCI). We therefore examined the use of preprocedural hydration to decrease the incidence of persistent RD. Methods Between 2012 and 2015, 1,230 consecutive patients undergoing PCI, except for patients with an eGFR ≥60 mL/min/1.73 m2, on dialysis, having acute myocardial infarction, or recently having started renin-angiotensin inhibitors, were screened (n=333). Before their index PCI, the 12-h saline group (n=103) received 1 mL/kg/h 0.9% sodium chloride for 12 hours, and the 1-h bicarbonate group (n=63) received 3 mL/kg 154 mEq/L sodium bicarbonate for 1 hour. The control group (n=167) received no pre-procedural hydration. The study outcome of kidney function decline was investigated using the percent-change (%-change) of the calculated creatinine clearance between the baseline value and the lowest value recorded three to six months after index PCI. Results There was less renal function deterioration in the saline group than in the control group, and the bicarbonate group showed deterioration similar to the other groups (%-change; 12-h saline 2.0±11.3% vs. control -5.6±12.6%, p<0.001; vs. 1-h bicarbonate -1.8±14.1%, p=0.18; 1-h bicarbonate vs. control, p=0.14 ANOVA). A multiple regression analysis adjusted for risk factors for persistent RD showed that saline hydration correlated independently with a higher %-change (r=0.262, p<0.001). Conclusion Preprocedural 12-h saline may be better than no preprocedural hydration in preventing mid-term renal insufficiency in CKD patients undergoing PCI.