Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.192
Filtrar
1.
Toxins (Basel) ; 13(5)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069405

RESUMO

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.


Assuntos
Disbiose/fisiopatologia , Microbioma Gastrointestinal , Insuficiência Renal Crônica/fisiopatologia , Animais , Doenças Cardiovasculares/fisiopatologia , Progressão da Doença , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Metilaminas/metabolismo
3.
Heart Fail Clin ; 17(3): 357-367, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051968

RESUMO

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) constitute a high-risk phenotype with significant morbidity and mortality and poor prognosis. Multiple proinflammatory comorbid conditions influence the pathogenesis of HFpEF and CKD. Renal dysfunction in HFpEF is a consequence of the complex interplay between hemodynamic factors, systemic congestion, inflammation, endothelial dysfunction, and neurohormonal mechanisms. In contrast to heart failure with reduced ejection fraction, there is a dearth of effective targeted therapies for HFpEF. Tailoring study design toward the different phenotypes and delving into their pathophysiology may be fruitful in development of effective phenotype-specific targeted pharmaceutical therapies.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/complicações , Insuficiência Renal Crônica/etiologia , Volume Sistólico/fisiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
4.
Medicine (Baltimore) ; 100(20): e25759, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011035

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a progressive and irreversible loss of kidney function. After stage 3, there will be increased risks of hypertension, heart failure, bone disease, anemia, gastrointestinal symptoms, and progression to end-stage kidney failure without proper intervention and treatment. Compound α-ketoacid tablets (KA) administration plays an important role in clinical CKD adjunctive therapy for patients with restricted protein intake. Bailing Capsule (BC), a commonly used Chinese patent medicine for renal diseases, could regulate human immune function, repair renal tubular epithelial cells, prevent renal tubular atrophy, and reduce kidney damage to improve renal function. In this study, we try to conduct a double-blinded, randomized, controlled trial to observe the efficacy and safety of BC combined with KA in treating patients with stage 3 CKD. METHODS: This is a double-blinded, randomized, controlled trial. Patients will be randomly divided into treatment group (BC and KT) and control group (BC-simulation and KT) in a 1:1 ratio according to random number table. The treatment course will be 8 weeks, and the changes of subjective symptoms, patient global assessment (PGA) scale, serum creatinine, cystatin C, and estimated glomerular filtration rate, all related adverse events, vital sign measurements, and physical examinations will be recorded. SPSS 21.0 will be used for data analysis. CONCLUSIONS: The results will show whether BC combined with KA could alleviate the symptoms of fatigue, anorexia, halitosis, nausea, itching, and edema, improve kidney function in patients with CKD at stage 3. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/24AJ7.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Cetoácidos/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Comprimidos , Resultado do Tratamento , Adulto Jovem
5.
Medicine (Baltimore) ; 100(20): e25903, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011057

RESUMO

BACKGROUND: Some new trials have reported the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation. Limited by small number of studies and insufficient outcomes, previous meta-analyses also failed to draw a consistent conclusion on this topic. We thus conducted a new meta-analysis to systematically analyze the effect of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation. METHODS: Two independent investigators followed The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct the present meta-analysis. From the inception to June 2021, the EMBASE, PubMed, Web of Science, and Cochrane Library electronic databases were searched using the key phrases "atrial fibrillation," "chronic kidney disease," "catheter ablation," "renal failure," "renal function," "renal insufficiency," "end-stage renal disease," and "dialysis" for all relevant English-language trials. Observational or randomized controlled trial focusing on assessing the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation was included. P < .05 was set as the significance level. RESULTS: Our hypothesis was that chronic kidney disease is associated with increased atrial fibrosis and a higher risk of arrhythmia recurrence and that restoration of normal rhythm through catheter ablation is associated with improved kidney function. REGISTRATION NUMBER: 10.17605/OSF.IO/3WJAE.


Assuntos
Fibrilação Atrial/epidemiologia , Ablação por Cateter/estatística & dados numéricos , Átrios do Coração/patologia , Insuficiência Renal Crônica/epidemiologia , Fibrilação Atrial/patologia , Fibrilação Atrial/cirurgia , Causalidade , Fibrose , Taxa de Filtração Glomerular/fisiologia , Átrios do Coração/cirurgia , Humanos , Metanálise como Assunto , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Revisões Sistemáticas como Assunto , Resultado do Tratamento
6.
Medicine (Baltimore) ; 100(20): e26009, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011099

RESUMO

ABSTRACT: Increased water intake correlated to lower vasopressin level and may benefit kidney function. However, results of previous studies were conflicted and inconclusive. We aimed to investigate the association between water intake and risk of chronic kidney disease (CKD) and albuminuria.In this cross-sectional study, the study population were adult participants of 2011-2012 National Health and Nutrition Examination Survey (NHANES) whose estimated glomerular filtration rate (eGFR) were ≥30 ml/min/1.73 m2. Data of water intake were obtained from the NHANES 24-h dietary recall questionnaire. Participants were divided into three groups based on volume of water intake: <500 (low, n = 1589), ≥500 to <1200 (moderate, n = 1359), and ≥1200 ml/day (high, n = 1685). CKD was defined as eGFR <60 ml/min/1.73 m2, and albuminuria as albumin-to-creatinine ratio (ACR) ≥30 mg/g.Our results showed that 377 out of 4633 participants had CKD; the prevalence inversely correlated to volume of water intake: 10.7% in low, 8.2% in moderate, and 5.6% in high intake groups (P < .001). Prevalence of albuminuria was also lower in high (9.5%) compared with moderate (12.8%) and low intake groups (14.1%), P < .001. Additionally, water intake positively correlated to eGFR and negatively correlated to urinary ACR, as well as plasma and urine osmolality. Multivariable logistic regression showed that low water intake group had higher risk of CKD (OR 1.35, 95% CI 1.01-1.82) and albuminuria when compared to high water intake group (OR 1.42, 95% CI 1.13-1.79).In conclusion, increased water intake was associated lower risk of CKD and albuminuria. Meticulous studies are needed to elucidate the underlying mechanisms.


Assuntos
Albuminúria/epidemiologia , Ingestão de Líquidos/fisiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Albuminúria/fisiopatologia , Albuminúria/urina , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Prevalência , Fatores de Proteção , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina
7.
Artigo em Inglês | MEDLINE | ID: mdl-33894116

RESUMO

World Kidney Day (WKD) is a global campaign to raise awareness of the importance of our kidneys to overall health and to reduce the frequency and impact of kidney disease and associated health problems worldwide. Kidney disease is a non-communicable disease (NCD) and currently affects around 850 million people worldwide. One in ten adults has chronic kidney disease (CKD). The global burden of CKD is increasing, and is projected to become the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume 2-3% of the annual healthcare budget in high-income countries. Crucially, kidney disease can be prevented and progression to end-stage kidney disease can be delayed with appropriate access to basic diagnostics and early treatment. This year World Kidney Day continues to raise awareness of the increasing burden of kidney diseases worldwide and to strive for kidney health for everyone, everywhere. During the pandemic with COVID 19 patients kidneys are also damaged, apart from the respiratory tract and other organs. It can lead to an increase in acute renal failure and consequent chronic kidney insufficiency, as well as number of deaths. Therefore, it is important to evaluate the renal function in each patient with COVID 19 virus. In the Republic of North Macedonia from 2006 to present day nephrologists and other medical personnel devoted to the early diagnosis, prevention and treatment of renal disease have participated in the activities of the World Kidney Day. These activities were supported by the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs, the Department of Nephrology at the Medical Faculty, the Macedonian Academy of Sciences and Arts, the Government of the Republic of North Macedonia, non-governmental nephrology organizations (NEFRON) and the media. There were lectures and presentation devoted to the various theme of the WKD, publications in journals, as well as activities for examination of the renal function of patients in the medical centers. The activities during the WKD contributed to the improvement of the nephrological protection of the citizens of the Republic of N. Macedonia.


Assuntos
Qualidade de Vida , Insuficiência Renal Crônica/fisiopatologia , Injúria Renal Aguda/fisiopatologia , COVID-19/fisiopatologia , Humanos , Transplante de Rim , Nefrologia , Assistência Centrada no Paciente , Diálise Renal , Insuficiência Renal Crônica/terapia , República da Macedônia do Norte , SARS-CoV-2
8.
Artigo em Inglês | MEDLINE | ID: covidwho-1204183

RESUMO

World Kidney Day (WKD) is a global campaign to raise awareness of the importance of our kidneys to overall health and to reduce the frequency and impact of kidney disease and associated health problems worldwide. Kidney disease is a non-communicable disease (NCD) and currently affects around 850 million people worldwide. One in ten adults has chronic kidney disease (CKD). The global burden of CKD is increasing, and is projected to become the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume 2-3% of the annual healthcare budget in high-income countries. Crucially, kidney disease can be prevented and progression to end-stage kidney disease can be delayed with appropriate access to basic diagnostics and early treatment. This year World Kidney Day continues to raise awareness of the increasing burden of kidney diseases worldwide and to strive for kidney health for everyone, everywhere. During the pandemic with COVID 19 patients kidneys are also damaged, apart from the respiratory tract and other organs. It can lead to an increase in acute renal failure and consequent chronic kidney insufficiency, as well as number of deaths. Therefore, it is important to evaluate the renal function in each patient with COVID 19 virus. In the Republic of North Macedonia from 2006 to present day nephrologists and other medical personnel devoted to the early diagnosis, prevention and treatment of renal disease have participated in the activities of the World Kidney Day. These activities were supported by the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs, the Department of Nephrology at the Medical Faculty, the Macedonian Academy of Sciences and Arts, the Government of the Republic of North Macedonia, non-governmental nephrology organizations (NEFRON) and the media. There were lectures and presentation devoted to the various theme of the WKD, publications in journals, as well as activities for examination of the renal function of patients in the medical centers. The activities during the WKD contributed to the improvement of the nephrological protection of the citizens of the Republic of N. Macedonia.


Assuntos
Qualidade de Vida , Insuficiência Renal Crônica/fisiopatologia , Injúria Renal Aguda/fisiopatologia , COVID-19/fisiopatologia , Humanos , Transplante de Rim , Nefrologia , Assistência Centrada no Paciente , Diálise Renal , Insuficiência Renal Crônica/terapia , República da Macedônia do Norte , SARS-CoV-2
9.
Nutrients ; 13(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917381

RESUMO

Multi-factors, such as anorexia, activation of renin-angiotensin system, inflammation, and metabolic acidosis, contribute to malnutrition in chronic kidney disease (CKD) patients. Most of these factors, contributing to the progression of malnutrition, worsen as CKD progresses. Protein restriction, used as a treatment for CKD, can reduce the risk of CKD progression, but may worsen the sarcopenia, a syndrome characterized by a progressive and systemic loss of muscle mass and strength. The concomitant rate of sarcopenia is higher in CKD patients than in the general population. Sarcopenia is also associated with mortality risk in CKD patients. Thus, it is important to determine whether protein restriction should be continued or loosened in CKD patients with sarcopenia. We may prioritize protein restriction in CKD patients with a high risk of end-stage kidney disease (ESKD), classified to stage G4 to G5, but may loosen protein restriction in ESKD-low risk CKD stage G3 patients with proteinuria <0.5 g/day, and rate of eGFR decline <3.0 mL/min/1.73 m2/year. However, the effect of increasing protein intake alone without exercise therapy may be limited in CKD patients with sarcopenia. The combination of exercise therapy and increased protein intake is effective in improving muscle mass and strength in CKD patients with sarcopenia. In the case of loosening protein restriction, it is safe to avoid protein intake of more than 1.5 g/kgBW/day. In CKD patients with high risk in ESKD, 0.8 g/kgBW/day may be a critical point of protein intake.


Assuntos
Proteínas na Dieta/administração & dosagem , Terapia por Exercício/métodos , Desnutrição Proteico-Calórica/prevenção & controle , Insuficiência Renal Crônica/terapia , Sarcopenia/prevenção & controle , Terapia Combinada/métodos , Proteínas na Dieta/efeitos adversos , Taxa de Filtração Glomerular/fisiologia , Humanos , Desnutrição Proteico-Calórica/epidemiologia , Desnutrição Proteico-Calórica/etiologia , Recomendações Nutricionais , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Sarcopenia/epidemiologia , Sarcopenia/etiologia
10.
Nutrients ; 13(5)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33922902

RESUMO

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.


Assuntos
Osso e Ossos/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Insuficiência Renal Crônica/fisiopatologia , Transplantados , Vitamina D/farmacologia , Humanos , Transplante de Rim , Vitamina D/administração & dosagem , Deficiência de Vitamina D/prevenção & controle , Vitaminas/administração & dosagem , Vitaminas/farmacologia
11.
Methods Mol Biol ; 2249: 179-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871844

RESUMO

Chronic diseases are now the major cause of ill health in both developed and developing countries. Chronic diseases evolve, over decades, from an early reversible phase, to a late stage of irreversible organ damage. Importantly, the trajectory of individual patients with a chronic disease is highly variable. This uncertainty causes substantial stress and difficulty for patients, care providers, and health systems. Clinical risk prediction models address this uncertainty by incorporating multiple variables to more precisely estimate the risk of adverse events for an individual patient. In the current chapter, we describe the general approach to developing a risk prediction model. We then illustrate how these methods are applied in the development and validation of the kidney failure risk equation (KFRE), which accurately predicts the risk of kidney failure in patients with chronic kidney disease stages 3-5.


Assuntos
Insuficiência Renal Crônica/complicações , Insuficiência Renal/diagnóstico , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Estudos Longitudinais , Masculino , Modelos Estatísticos , Prognóstico , Insuficiência Renal/etiologia , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco
12.
Nutr Metab Cardiovasc Dis ; 31(5): 1445-1453, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33812736

RESUMO

BACKGROUND AND AIMS: How Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes. METHODS AND RESULTS: This is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1-2 vs 3-5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01). CONCLUSIONS: Low MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.


Assuntos
Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Saudável , Dieta Mediterrânea , Rim/fisiopatologia , Qualidade de Vida , Insuficiência Renal Crônica/dietoterapia , Idoso , Fatores de Risco Cardiometabólico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Cooperação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Tempo
14.
Medicine (Baltimore) ; 100(16): e25633, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879740

RESUMO

ABSTRACT: Our previous study demonstrated that patients with end-stage renal disease had decreased structural and functional brain connectivity, and there was a significant association between brain connectivity and cognitive function. The aim of this study was to evaluate the alterations of structural and functional connectivity using graph theoretical analysis in neurologically asymptomatic patients with relatively early-stage chronic kidney disease (CKD).We enrolled 18 neurologically asymptomatic patients with early CKD and 28 healthy controls. All the subjects underwent diffusion-tension imaging and resting functional magnetic resonance imaging. We calculated structural and functional connectivity based on diffusion-tension imaging and resting functional magnetic resonance imaging using a graph theoretical analysis. Then, we investigated differences of structural and functional connectivity between the CKD patients and the healthy controls.All the measures of structural connectivity were significantly different between the patients with CKD and healthy controls. The global efficiency, local efficiency, mean clustering coefficient, and small-worldness index were decreased, whereas the characteristic path length was increased in the patients with CKD compared with healthy controls. The structural betweenness centrality of the left calcarine and right posterior cingulum was also significantly different from that in healthy participants. However, all the measures of global functional connectivity in patients with CKD were not different from those in healthy controls. In patients with CKD, the functional betweenness centrality of the right insular cortex, right occipital pole, and right thalamus was significantly different from that in healthy participants.There are significant alterations of the global structural connectivity between the patients with CKD and the healthy subjects, whereas the global functional connectivity of the brain network is preserved. We find that the efficiency of the structural brain network is decreased in the patients with CKD.


Assuntos
Encéfalo/fisiopatologia , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Vias Neurais/fisiopatologia , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/fisiopatologia , Idoso , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Insuficiência Renal Crônica/psicologia , Descanso/fisiologia
15.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807408

RESUMO

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFß1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2ß1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFß1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2ß1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFß1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2ß1 signaling, ahead of establishing Peptide 5 as a potential intervention.


Assuntos
Colágeno Tipo I/metabolismo , Conexina 43/metabolismo , Túbulos Renais Proximais/metabolismo , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Adesão Celular , Linhagem Celular , Células Cultivadas , Colágeno Tipo I/fisiologia , Conexina 43/fisiologia , Conexinas/metabolismo , Citocinas , Células Epiteliais/metabolismo , Humanos , Integrina alfa2beta1/metabolismo , Integrina alfa2beta1/fisiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo
16.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799511

RESUMO

In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-ß-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.


Assuntos
Receptores de Lipopolissacarídeos/genética , Lipoproteínas HDL/farmacologia , Neutrófilos/efeitos dos fármacos , Insuficiência Renal Crônica/genética , Uremia/genética , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Lipoproteínas HDL/isolamento & purificação , Masculino , Microdomínios da Membrana/química , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/metabolismo , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Cultura Primária de Células , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo , Uremia/metabolismo , Uremia/fisiopatologia , Uremia/terapia , beta-Ciclodextrinas/farmacologia , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
17.
Nutrients ; 13(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804453

RESUMO

Vitamin K (VK) and vitamin D (VD) deficiency/insufficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and a higher risk of fractures. CKD patients, with disturbances in VK and VD metabolism, do not have sufficient levels of these vitamins for maintaining normal bone formation and mineralization. So far, there has been no consensus on what serum VK and VD levels can be considered sufficient in this particular population. Moreover, there are no clear guidelines how supplementation of these vitamins should be carried out in the course of CKD. Based on the existing results of preclinical studies and clinical evidence, this review intends to discuss the effect of VK and VD on bone remodeling in CKD. Although the mechanisms of action and the effects of these vitamins on bone are distinct, we try to find evidence for synergy between them in relation to bone metabolism, to answer the question of whether combined supplementation of VK and VD will be more beneficial for bone health in the CKD population than administering each of these vitamins separately.


Assuntos
Doenças Ósseas Metabólicas/terapia , Suplementos Nutricionais , Insuficiência Renal Crônica/terapia , Vitamina D/administração & dosagem , Vitamina K/administração & dosagem , Vitaminas/administração & dosagem , Adulto , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/etiologia , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Quimioterapia Combinada , Feminino , Humanos , Masculino , Camundongos , Ratos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/terapia
18.
Nefrología (Madrid) ; 41(2): 95-101, mar.-abr. 2021. graf, tab
Artigo em Inglês | IBECS | ID: ibc-201563

RESUMO

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of "Living Well with Kidney Disease" in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness programme for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programmes, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policy makers, applicable to both developed and developing countries


No disponible


Assuntos
Humanos , Insuficiência Renal Crônica/fisiopatologia , Participação do Paciente/métodos , Cuidadores , Qualidade de Vida , Medidas de Resultados Relatados pelo Paciente , Hemodiálise no Domicílio
19.
Am J Physiol Heart Circ Physiol ; 320(5): H1802-H1812, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710924

RESUMO

Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using pressure-flow relations, wave separation analysis can be used to decompose aortic pressure waveforms into forward- (Pf) and backward-traveling (Pb) components. Reflection magnitude, the ratio of pressure amplitudes (RM = Pb/Pf), is a predictor of heart failure and all-cause mortality. Aortic flow can be measured via Doppler echocardiography or estimated using a triangular flow waveform; however, the latter may underestimate the flow waveform convexity and overestimate Pb and RM. We sought to determine the accuracy of a personalized synthetic physiologic flow waveform, compared with triangular and measured flow waveforms, for estimating wave reflection indices in 49 healthy young (27 ± 6 yr) and 29 older adults [66 ± 6 yr; 20 healthy, 9 chronic kidney disease (CKD)]. Aortic pressure and measured flow waveforms were acquired via radial tonometry and echocardiography, respectively. Triangular and physiologic flow waveforms were constructed from aortic pressure waveforms. Compared with the measured flow waveform, the triangular waveform underestimated Pf in older, but not young, adults and overestimated Pb and RM in both groups. The physiologic waveform was equivalent to measured flow in deriving all wave reflection indices and yielded smaller mean absolute biases than the triangular waveform in all instances (P < 0.05). Lastly, central pulse pressure was associated with triangular, but not physiologic, mean biases for Pb and RM independent of age or central arterial stiffness (P < 0.05). These findings support the use of personalized physiologic flow waveforms as a more robust alternative to triangular flow waveforms when true flow cannot be measured.NEW & NOTEWORTHY We demonstrate that triangular flow waveforms overestimate wave reflection indices, particularly at higher central pulse pressures independent of age or carotid-femoral pulse wave velocity. In contrast, personalized physiologic flow waveforms provide equivalent wave reflection estimates as measured flow waveforms, thereby offering a more robust alternative to triangulation when aortic flow cannot be measured.


Assuntos
Aorta/fisiologia , Pressão Arterial , Determinação da Pressão Arterial , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Velocidade da Onda de Pulso Carótido-Femoral , Estudos de Casos e Controles , Ecocardiografia Doppler de Pulso , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Fatores de Tempo , Rigidez Vascular , Adulto Jovem
20.
JAMA Netw Open ; 4(3): e213296, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33769507

RESUMO

Importance: Chronic kidney disease (CKD) is prevalent in the population of patients undergoing transcatheter aortic valve replacement (TAVR). Data on the association of TAVR with kidney function are scarce, as are data on the relationship between changes in kidney function after TAVR and mortality. Objective: To describe the changes in kidney function (both periprocedural and at steady state) after TAVR and to explore the association of TAVR with midterm mortality. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted at a public, tertiary academic medical center, which serves as a regional referral center for valvular heart interventions. Consecutive cases of patients undergoing TAVR from November 5, 2008, to December 31, 2019, were included in the study, with available baseline and post-TAVR data on kidney function. Exposures: Steady state (1 month) change in kidney function after TAVR. Significant improvement or deterioration in renal function was defined as a greater than or equal to 10% change in estimated glomerular filtration rate (eGFR). Main Outcomes and Measures: Overall mortality at 2-year follow-up. Results: A total of 894 patients (mean [SD] age, 82.2 [7.1] years; 452 women ([51.2%]) were evaluated. A total of 362 patients (40.5%) were treated from 2017 to 2019, 348 patients (38.9%) were treated from 2013 to 2016, and 184 patients (20.5%) were treated from 2008 and 2012. Patients had a mean (SD) Society of Thoracic Surgeons (STS) score of 5.2% (4.0%) and a mean (SD) eGFR of 65.1 (23.1) mL/min/1.73 m2. Acute kidney injury occurred in 115 (11.1%) patients by 48 hours, of whom 73 (63.5%) resolved by discharge. One month after TAVR, eGFR improved by at least 10% in 329 patients (36.8%) and deteriorated by at least 10% in 233 patients (26.1%). Overall, CKD stage remained stable or improved in 720 patients (80.6%), and only 5 patients (0.97%) progressed to stage 5 CKD 1 month after TAVR. A deterioration of 10% or greater in eGFR 1 month after TAVR was associated with a hazard ratio of 2.16 (95% CI, 1.24-5.24; P = .04) at 2-year mortality. Patients who showed CKD status resolution (eGFR improvement to >60 mL/min/1.73 m2 after TAVR) had a similar 2-year mortality to those with baseline eGFR greater than 60 mL/min/1.73 m2 and vice versa. Factors associated with steady state CKD status resolution after TAVR included lower STS score, higher left ventricular ejection fraction, higher baseline eGFR, no acute kidney injury at discharge from the TAVR admission, and lower contrast-eGFR ratio. Conclusions and Relevance: In this cohort study, kidney outcomes after TAVR were reassuring; greater than 80% of patients showed stable or improved kidney function 1 month after the procedure. Improvement in kidney function was associated with a lower 2-year mortality, whereas deterioration in kidney function was associated with increased mortality. Our data suggest that cardiorenal syndrome was a possible cause of CKD in patients in need of TAVR and that there was potential for improvement in both renal and cardiac function after this procedure.


Assuntos
Estenose da Valva Aórtica/cirurgia , Taxa de Filtração Glomerular/fisiologia , Rim/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco/métodos , Substituição da Valva Aórtica Transcateter/métodos , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Israel/epidemiologia , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Sistema de Registros , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...