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1.
Medicine (Baltimore) ; 99(51): e23043, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371059

RESUMO

INTRODUCTION: A large number of patients will experience pruritus after uremia. Medicine is the preferred treatment for many doctors, but the effectiveness and safety of different medicines for uremia pruritus has not yet been comprehensively compared, based on network meta-analysis. METHODS AND ANALYSIS: According to the retrieval strategy, two team members independently searched the literature in 7 databases, and imported the retrieval results into the EndNote Software AQ8 (V.X9). After deleting repeated articles, they read the abstract and the full text, selected the articles that met the inclusion criteria and extracted valid information. The main results were visual analogue scale (VAS) and the secondary results were verbal rating scale (VRS), Dirk R Kuypers score, and adverse event incidence. The methodological quality evaluation was conducted from 7 aspects, according to The Cochrane Collaborative Tool, Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) was used for data analysis. The level of evidence will be assessed by the Grading of Recommendations, Development and Evaluation (GRADE) instrument). RESULTS: The results will rank the efficacy of drugs used to treat uremic pruritus and assess their safety. CONCLUSION: This study is the first to compare the efficacy and safety of medicines for uremic pruritus based on network analysis and will provide evidence and ideas for the treatment of uremic pruritus. INPLASY REGISTRATION NUMBER: No. INPLASY202090103.


Assuntos
Medicamentos sob Prescrição/efeitos adversos , Prurido/tratamento farmacológico , Prurido/etiologia , Uremia/complicações , Fatores Etários , Humanos , Metanálise em Rede , Medicamentos sob Prescrição/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores Sexuais , Escala Visual Analógica
3.
Medicine (Baltimore) ; 99(24): e20401, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541461

RESUMO

Depression may hamper the immune system and nutritional status, which leads to poor outcomes of treatment. It is very common in dialysis patients. There are the numbers of parameters affected by the depression of patients and available studies are not enough to define the association between biological parameters and depression in the dialysis population. The purposes of the study were to find the prevalence of depression and association of it with the biochemical abnormalities in the dialysis patients.The selected battery of tests (clinician-administered questionnaires) were applied to dialysis patients (test cohort, n = 298) and caregivers (control cohort, n = 202) for establishing depression. The demographic and clinical conditions of participants were also collected. Univariate analysis followed by multiple regression analysis was performed for demographical parameters, clinical conditions, and laboratory results for the detection of association of them with depression. The abnormal test considered as more than 2 SD of mean below the normal value. Out of all tests, at least 2 abnormal tests were considered as mild depression. More than half of abnormal parameters among all tests were considered as moderate depression and all abnormal parameters were considered as severe depression.There was a significant difference for all the test between dialysis patients and the caregivers (P < .0001 for all). The half (153 out of 298) of dialysis patients were depressive and clinically asymptomatic. 70 (23%) dialysis patients were mild depressive, 45 (15%) dialysis patients were moderate depressive, and 38 (13%) dialysis patients were severely depressive. Serum phosphate (P = .023), level of parathyroid hormone (P = .021), and urea reduction rate (P = .048) were directly associated with depression.Biochemical abnormalities (serum phosphate level, parathyroid hormone, and urea reduction rate) were independent predictors of depression in the dialysis population.Level of evidence: III.


Assuntos
Depressão/psicologia , Diálise Renal/psicologia , Uremia/terapia , Adulto , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Cuidadores/psicologia , Estudos de Casos e Controles , China/epidemiologia , China/etnologia , Estudos de Coortes , Depressão/sangue , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Prevalência , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Uremia/complicações
4.
Med Sci Monit ; 26: e919086, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040471

RESUMO

BACKGROUND This study aimed to investigate the effects of resveratrol on kidney function in a rat model of uremia and the expression of heat shock proteins. MATERIAL AND METHODS The rat model of uremia was developed by 5/6 nephrectomy of Sprague-Dawley rats. The Hsp70 inhibitor MKT-077, a rhodacyanine dye, was used. The study groups included rats with sham surgery (the sham group), the rat model of uremia (the model group), the solvent-treated control group (the control group), the rat model treated with resveratrol group (the resveratrol group), the rat model treated with MKT-077 (the MKT-077 group), and the resveratrol+MKT-077 group. Kidney tissues were studied histologically. Renal cell apoptosis was detected by the TUNEL method. Expression of p53, Bax, and Bcl-2 mRNA and protein were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. RESULTS Compared with the sham group, the expression levels of heat shock proteins Hsp70, Hsp90, Hsp27, Hsp25, Hsp40, and Hsp60 in the kidney of the rat model group increased to different degrees. Compared with the model group, the Hsp70 levels in the resveratrol group were significantly increased (p<0.05). Compared with the model group, treatment with MKT-077 reduced the survival rate of rats, which was increased following resveratrol treatment. Compared with the resveratrol group, renal function in the resveratrol+MKT-077 group was significantly reduced (p<0.05). CONCLUSIONS In a rat model of uremia, resveratrol reduced renal injury and improved both renal function and survival, which were associated with increased expression of Hsp70.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Rim/lesões , Rim/metabolismo , Resveratrol/uso terapêutico , Uremia/complicações , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Proteínas de Choque Térmico HSP70/genética , Rim/patologia , Rim/fisiopatologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Resveratrol/farmacologia , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Uremia/sangue , Uremia/genética , Uremia/fisiopatologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
5.
Arch Med Res ; 51(1): 21-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32086105

RESUMO

OBJETIVE: Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia. MATERIAL AND METHODS: Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry. RESULTS: Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment. CONCLUSIONS: These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.


Assuntos
Apoptose/efeitos dos fármacos , Indicã/farmacologia , Mioblastos/efeitos dos fármacos , Sarcopenia/induzido quimicamente , Uremia/induzido quimicamente , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Camundongos , Células Musculares/efeitos dos fármacos , Células Musculares/fisiologia , Mioblastos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sarcopenia/complicações , Toxinas Biológicas/metabolismo , Toxinas Biológicas/farmacologia , Regulação para Cima/efeitos dos fármacos , Uremia/complicações
6.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069992

RESUMO

In recent years, Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions, including cardiac hypertrophy and uremic cardiomyopathy. Cardiotonic steroids (CTS), specific ligands of Na/K-ATPase, regulate its enzymatic activity (at higher concentrations) and signaling function (at lower concentrations without significantly affecting its enzymatic activity) and increase reactive oxygen species (ROS) generation. On the other hand, an increase in ROS alone also regulates the Na/K-ATPase enzymatic activity and signaling function. We termed this phenomenon the Na/K-ATPase-mediated oxidant-amplification loop, in which oxidative stress regulates both the Na/K-ATPase activity and signaling. Most recently, we also demonstrated that this amplification loop is involved in the development of uremic cardiomyopathy. This review aims to evaluate the redox-sensitive Na/K-ATPase-mediated oxidant amplification loop and uremic cardiomyopathy.


Assuntos
Cardiomiopatias/genética , Estresse Oxidativo/genética , ATPase Trocadora de Sódio-Potássio/genética , Uremia/genética , Glicosídeos Cardíacos/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Uremia/complicações , Uremia/tratamento farmacológico , Uremia/patologia
7.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32070049

RESUMO

Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are two protein bound uraemic toxins accumulated in chronic kidney disease (CKD) and associated with adverse outcomes. The purpose of this study isto evaluate the effect of the new activated charcoal, CharXgen, on renal function protection and lowering serum uraemic toxins in CKD animal model. The physical character of CharXgen was analyzed before and after activation procedure by Scanning Electron Microscope (SEM) and X-ray diffractometer (XRD). The effect of CharXgen on biochemistry and lowering uremic toxins was evaluated by in vitro binding assay and CKD animal model. CharXgen have high interior surface area analyzed by SEM and XRD and have been produced from local bamboo after an activation process. CharXgen was able to effectively absorb IS, p-cresol and phosphate in an in vitro gastrointestinal tract simulation study. The animal study showed that CharXgen did not cause intestine blackening. Serum albuminand liver function did not change after feeding with CharXgen. Moreover, renal function was improved in CKD rats fed with CharXgen as compared to the CKD group, and there were no significant differences in the CKD and the CKD + AST-120 groups. Serum IS and PCS were higher in the CKD group and lower in rats treated with CharXgen and AST-120. In rats treated with CharXgen, Fibroblast growth factor 23 was significantly decreased as compared to the CKD group. This change cannot be found in rats fed with AST-120.It indicates that CharXgen is a new safe and non-toxic activated charcoal having potential in attenuating renal function deterioration and lowering protein-bound uraemic toxins. Whether the introduction of this new charcoal could further have renal protection in CKD patients will need to be investigated further.


Assuntos
Carvão Vegetal/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Sasa/química , Toxinas Biológicas/sangue , Uremia/tratamento farmacológico , Alginatos/química , Alginatos/farmacologia , Animais , Carbono/farmacologia , Linhagem Celular , Cresóis/farmacologia , Modelos Animais de Doenças , Humanos , Indicã/farmacologia , Microscopia Eletrônica de Varredura , Microesferas , Óxidos/farmacologia , Ratos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Ésteres do Ácido Sulfúrico/farmacologia , Uremia/sangue , Uremia/complicações , Uremia/patologia
8.
Intern Med ; 59(9): 1141-1148, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32051383

RESUMO

Objective Uremic toxins are known risk factors for cancer in patients undergoing hemodialysis (HD). Although adequate removal of uremic toxins might reduce the cancer risk by improving subclinical uremia, the relationship between the dialysis dose and risk of cancer death in patients undergoing HD remains unclear. Methods In this prospective observational study, 3,450 patients undergoing HD were followed up for 4 years. The primary outcome was cancer death. Patients were divided into quartiles according to their baseline Kt/V levels. The association between the Kt/V levels and risk of cancer death was estimated using the Kaplan-Meier method and Cox proportional-hazards model. Results A total of 111 patients (3.2%) died from cancer during the 4-year observational period. The 4-year survival rate decreased linearly with decreasing Kt/V. The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer death were 2.23 (95% CI, 1.13-4.56), 1.77 (0.88-3.63), and 1.89 (1.04-3.56) in quartile (Q) 1, Q2, and Q3, respectively, compared with patients in the highest Kt/V category (Q4) (p for trend = 0.06). Every 0.1 increase in Kt/V was associated with a reduction of 8% in cancer death (HR 0.92, 95% CI, 0.85-0.99). Conclusion A lower dialysis dose might be associated with a higher risk of cancer death in patients undergoing HD. Kt/V is a simple indicator of dialysis dose used in clinical practice and might be a useful modifiable factor for predicting the risk of cancer death. Further basic and interventional studies are needed to confirm the apparent reduction in cancer death associated with increasing the dialysis dose.


Assuntos
Falência Renal Crônica/terapia , Neoplasias/epidemiologia , Diálise Renal , Idoso , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Falência Renal Crônica/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Uremia/complicações
9.
Internist (Berl) ; 61(4): 340-348, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31578597

RESUMO

Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity and mortality. This is mediated by the high prevalence of traditional cardiovascular risk factors in patients with CKD such as arterial hypertension and diabetes mellitus, but also by the presence of CKD-specific so-called nontraditional cardiovascular risk factors such as vascular calcification, uremic toxins, uremic dyslipidemia as well as inflammation and oxidative stress. Therefore, the primary and secondary prevention of cardiovascular disease represents an integral part of nephrology. This entails optimal control of blood pressure and diabetes, therapy of the uremic dyslipidemia as well as lifestyle-modifying factors such as weight reduction and smoking cessation.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/epidemiologia , Insuficiência Renal Crônica/complicações , Toxinas Biológicas/sangue , Uremia/complicações , Pressão Sanguínea/fisiologia , Cálcio/metabolismo , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/etiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertensão/prevenção & controle , Inflamação/complicações , Estresse Oxidativo , Fatores de Risco , Uremia/epidemiologia , Uremia/metabolismo , Calcificação Vascular/complicações , Calcificação Vascular/epidemiologia , Rigidez Vascular
10.
Nephrol Dial Transplant ; 35(4): 624-632, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30202981

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) are more prone to develop premature age-related diseases. Data on immune senescence are scarce in CKD populations, except in end-stage renal disease and dialysis. We designed a longitudinal prospective study to evaluate immune senescence at different CKD stages and its influence on CKD patient outcomes. METHODS: Clinical and biological data collections were performed on 222 patients at different CKD stages [1-2 (n = 85), 4 (n = 53) and 5 (n = 84)]. Immune senescence biomarkers were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, γH2A.X) or by quantitative polymerase chain reaction [relative telomere length (RTL)] on peripheral blood mononuclear cells and analysed according to CKD stages and outcomes. RESULTS: CKD was associated with an increase in immune senescence and inflammation biomarkers, as follows: low thymic output (197 ± 25 versus 88 ± 13 versus 73 ± 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of terminally differentiated T cells (CD8+CD28-CD57+) (24 ± 18 versus 32 ± 17 versus 35 ± 19%) restricted to cytomegalovirus-positive patients, telomere shortening (1.11 ± 0.36 versus 0.78 ± 0.24 versus 0.97 ± 0.21 telomere:single copy ratio) and an increase in C-reactive protein levels [median 2.9 (range 1.8-4.9) versus 5.1 (27-9.6) versus 6.2 (3.4-10.5) mg/L]. In multivariate analysis, shorter RTL was associated with death {hazard ratio [HR] 4.12 [95% confidence interval (CI) 1.44-11.75]}. Low thymic output was associated with infections [HR 1.79 (95% CI (1.34-9.58)] and terminally differentiated CD8+ T-cell expansion with a risk of cardiovascular events [CEs; HR 4.86 (95% CI 1.72-13.72)]. CONCLUSION: CKD was associated with premature immune ageing. Each of these alterations increased the risk of specific age-related diseases, such as RTL and death, thymic function and infections and terminally differentiated CD8+ T-cell expansion and CEs.


Assuntos
Envelhecimento/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Leucócitos Mononucleares/imunologia , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/mortalidade , Uremia/complicações , Idoso , Envelhecimento/imunologia , Biomarcadores/análise , Feminino , França/epidemiologia , Humanos , Estudos Longitudinais , Ativação Linfocitária , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/patologia , Taxa de Sobrevida , Telômero/genética
11.
N Engl J Med ; 382(3): 222-232, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31702883

RESUMO

BACKGROUND: Difelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients undergoing hemodialysis who had moderate-to-severe pruritus to receive either intravenous difelikefalin (at a dose of 0.5 µg per kilogram of body weight) or placebo three times per week for 12 weeks. The primary outcome was the percentage of patients with an improvement (decrease) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS; scores range from 0 to 10, with higher scores indicating greater itch intensity). The secondary outcomes included the change from baseline in itch-related quality-of-life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety. RESULTS: A total of 378 patients underwent randomization. A total of 82 of 158 patients (51.9%) in the difelikefalin group had a decrease of at least 3 points in the WI-NRS score (primary outcome), as compared with 51 of 165 (30.9%) in the placebo group. The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.1% in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001). Difelikefalin also resulted in a significant improvement from baseline to week 12 in itch-related quality of life as measured by the 5-D itch scale and the Skindex-10 scale. The imputed percentage of patients with a decrease of at least 4 points in the WI-NRS score at week 12 was significantly greater in the difelikefalin group than in the placebo group (37.1% [observed data: 64 of 158 patients] vs. 17.9% [observed data: 35 of 165 patients], P<0.001). Diarrhea, dizziness, and vomiting were more common in the difelikefalin group than in the placebo group. CONCLUSIONS: Patients treated with difelikefalin had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo. (Funded by Cara Therapeutics; KALM-1 ClinicalTrials.gov number, NCT03422653.).


Assuntos
Falência Renal Crônica/complicações , Piperidinas/uso terapêutico , Prurido/tratamento farmacológico , Receptores Opioides/agonistas , Diálise Renal , Uremia/complicações , Adulto , Método Duplo-Cego , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Prurido/etiologia , Qualidade de Vida , Resultado do Tratamento
13.
Hemodial Int ; 24(1): E10-E12, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31840926

RESUMO

Neurological complications are common in patients with acute or chronic renal failure, especially when there is marked reduction in the glomerular filtration rate (GFR). One such clinical syndrome, uremic encephalopathy (UE), occurs due to widespread dysfunction of central nervous system (CNS). It manifests with myriad clinical features and usually is suggested by bedside elicitation of asterixis (flapping tremor). Symptomatic involvement of the basal ganglia manifesting as choreoathetosis and clinical and radiological resolution with hemodialysis has been reported in the medical literature, but only rarely. The present report details such a case.


Assuntos
Edema Encefálico/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Doenças do Sistema Nervoso/etiologia , Diálise Renal/métodos , Uremia/complicações , Uremia/diagnóstico por imagem , Edema Encefálico/patologia , Feminino , Humanos , Pessoa de Meia-Idade
14.
Nephrol Dial Transplant ; 35(1): 65-73, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715488

RESUMO

BACKGROUND: Optimal phosphate control is an unmet need in chronic kidney disease (CKD). High serum phosphate increases calcification burden and is associated with mortality and cardiovascular disease in CKD. Nicotinamide (NA) alone or in combination with calcium-free phosphate binders might be a strategy to reduce phosphate levels and calcification and thus impact cardiovascular disease in CKD. METHODS: We studied the effect of NA alone and in combination with magnesium carbonate (MgCO3) as a potential novel treatment strategy. CKD was induced in dilute brown non-agouti/2 mice by subtotal nephrectomy followed by a high-phosphate diet (HP) and 7 weeks of treatment with NA, MgCO3 or their combination. Control mice underwent subtotal nephrectomy and received an HP or underwent sham surgery and received standard chow plus NA. RESULTS: CKD mice showed increased serum fibroblast growth factor 23 and calcium-phosphate product that was normalized by all treatment regimes. NA alone increased soft tissue and vascular calcification, whereas any treatment with MgCO3 significantly reduced calcification severity in CKD. While MgCO3 supplementation alone resulted in decreased calcification severity, it resulted in increased intestinal expression of the phosphate transporters type II sodium-dependent phosphate transporter 1 (Pit-1). Combined therapy of MgCO3 and NA reduced tissue calcification and normalized expression levels of intestinal phosphate transporter proteins. CONCLUSIONS: In conclusion, the data indicate that NA increases while MgCO3 reduces ectopic calcification severity. Augmented expression of intestinal phosphate transporters by MgCO3 treatment was abolished by the addition of NA. However, the clinical relevance of the latter remains to be explored. Importantly, the data suggest no benefit of NA regarding treatment of calcification in addition to MgCO3.


Assuntos
Magnésio/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Niacinamida/farmacologia , Insuficiência Renal Crônica/complicações , Uremia/complicações , Calcificação Vascular/prevenção & controle , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Músculo Liso Vascular/citologia , Calcificação Vascular/etiologia , Complexo Vitamínico B/farmacologia
15.
BMC Nephrol ; 20(1): 463, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830919

RESUMO

BACKGROUND: Point-of-Care Ultrasound (PoCUS) is considered as an extension of clinicians' patient care and can be integrated into daily clinical practice. Dyspnea is a common presentation in uremic patients. With the aids of PoCUS and integrated assessments of lung, heart and inferior vena cava (IVC), the etiology of dyspnea in uremic patients can be determined earlier. CASE PRESENTATION: A 67-year-old woman presented with progressive shortness of breath and bilateral legs edema for 3 weeks. The laboratory data revealed marked elevated level of serum creatinine and blood urea. A large amount of pericardial effusion was timely detected by PoCUS. Uremic pericarditis was suspected. Emergent hemodialysis was initiated and her symptoms improved. CONCLUSIONS: PoCUS is a noninvasive and cost-effective imaging modality and it has been popular in the emergency department (ED). In uremic patients presenting with dyspnea, the integration of PoCUS into traditional physical examinations help emergency physicians narrow down the differential diagnoses.


Assuntos
Gerenciamento Clínico , Dispneia/diagnóstico por imagem , Dispneia/terapia , Sistemas Automatizados de Assistência Junto ao Leito , Uremia/diagnóstico por imagem , Uremia/terapia , Idoso , Dispneia/complicações , Eletrocardiografia/métodos , Feminino , Humanos , Ultrassonografia de Intervenção/métodos , Uremia/complicações
16.
Adv Chronic Kidney Dis ; 26(6): 437-444, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31831122

RESUMO

Vascular calcification (VC) is common in advanced chronic kidney disease (CKD), contributes to cardiovascular disease (CVD), and associates with increased mortality. Major risk factors for VC in CKD are increasing age, dialysis vintage, and positive net calcium-phosphate balance. To date, no specific therapy that prevents progression or facilitates regression of VC beyond careful attention to calcium and phosphate balance exists. Accumulating evidence demonstrates that CKD patients may incur subclinical vitamin K deficiency. This deficiency may be induced by exhaustion of vitamin K due to its high requirement by vitamin K-dependent proteins to inhibit VC. This review analyzes the pathophysiological mechanisms and clinical consequences of vitamin K deficiency with emphasis on its involvement on vascular calcification in CKD and end-stage renal disease and its relationship to the bone-vascular axis.


Assuntos
Falência Renal Crônica/metabolismo , Uremia/metabolismo , Calcificação Vascular/metabolismo , Deficiência de Vitamina K/complicações , Vitamina K/metabolismo , Humanos , Falência Renal Crônica/complicações , Uremia/complicações , Calcificação Vascular/etiologia , Deficiência de Vitamina K/metabolismo
17.
Adv Chronic Kidney Dis ; 26(6): 427-436, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31831121

RESUMO

Considerable technological advances have enabled the identification and linkage of nonenzymatic post-translationally modified proteins to the pathogenesis of cardiovascular disease (CVD) in patients with kidney failure. Through processes such as the nonenzymatic carbamylation reaction as well as the formation of advanced glycation end products, we now know that protein modifications are invariably associated with the development of CVD beyond a mere epiphenomenon and this has become an important focus of nephrology research in recent years. Although the specific mechanisms by which protein modifications occurring in kidney failure that may contribute to CVD are diverse and include pathways such as inflammation and fibrosis, vascular calcification has emerged as a distinct pathological sequelae of protein modifications. In this review, we consider the biological mechanisms and clinical relevance of protein carbamylation and advanced glycation end products in CVD development with a focus on vascular calcification.


Assuntos
Doenças Cardiovasculares/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Falência Renal Crônica/metabolismo , Carbamilação de Proteínas , Processamento de Proteína Pós-Traducional , Calcificação Vascular/metabolismo , Animais , Artérias , Humanos , Falência Renal Crônica/complicações , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Uremia/complicações , Uremia/metabolismo , Calcificação Vascular/etiologia
18.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(12): 924-927, 2019 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-31887819

RESUMO

Objective: To investigate the etiology, characteristics and prevention of severe facial deformity in patients with uremia entering the dialysis stage. Methods: Four cases with uremia in the dialysis stage who presented with severe facial deformity between October 2011 and November 2018 were reviewed, including 3 males and 1 female. The ages were 31, 15, 51 and 61, respectively. The general information, clinical symptoms, biochemical indicators, relevant imaging indicators, diagnoses, treatments and efficacies of the 4 patients admitted to the First Affiliated Hospital of Anhui Medical University were collected. Results: All the 4 patients appeared obviously shorter, accompanied by a certain degree of decline in self-care ability, multiple bone and joint pain and severe facial deformity. They presented with significantly increased serum levels of alkaline phosphatase, calcium, phosphorus and parathyroid hormone, and parathyroid hormone level>2 500 pg/ml.Ultrasonography and (99)Tc(m) radionuclide scan showed in situ or ectopic hyperplasia of parathyroid tissue. Bone radiography showed local decrease of bone mineral density and cystic changes.After parathyroidectomy, the serum levels of alkaline phosphatase, parathyroid hormone, calciumand phosphorus decreased significantly, while bone pain symptoms and facial deformities gradually improved. Conclusion: Secondary hyperparathyroidism is a serious complication in patients with dialysis and few of patients may have severe facial deformity (Sagliker syndrome) affecting their normal life and social activities. Parathyroidectomy can improve the facial deformity and the quality of life of patients.


Assuntos
Hiperparatireoidismo Secundário , Uremia , Adolescente , Adulto , Cálcio , Feminino , Humanos , Hiperparatireoidismo Secundário/complicações , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides , Hormônio Paratireóideo , Paratireoidectomia , Qualidade de Vida , Uremia/complicações
19.
Int Urol Nephrol ; 51(12): 2209-2226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576489

RESUMO

Chronic kidney disease (CKD) is a worldwide health problem, because it is one of the most common complications of metabolic diseases including obesity and type 2 diabetes. Patients with CKD also develop other comorbidities, such as hypertension, hyperlipidemias, liver and cardiovascular diseases, gastrointestinal problems, and cognitive deterioration, which worsens their health. Therapy includes reducing comorbidities or using replacement therapy, such as peritoneal dialysis, hemodialysis, and organ transplant. Health care systems are searching for alternative treatments for CKD patients to mitigate or retard their progression. One new topic is the study of uremic toxins (UT), which are excessively produced during CKD as products of food metabolism or as a result of the loss of renal function that have a negative impact on the kidneys and other organs. High urea concentrations significantly modify the microbiota in the gut also, cause a decrease in bacterial strains that produce anti-inflammatory and fuel molecules and an increase in bacterial strains that can metabolize urea, but also produce UT, including indoxyl sulfate and p-cresol sulfate. UT activates several cellular processes that induce oxidative environments, inflammation, proliferation, fibrosis development, and apoptosis; these processes mainly occur in the gut, heart, and kidney. The study of the microbiota during CKD allowed for the implementation of therapy schemes to try to reduce the circulating concentrations of UT and reduce the damage. The objective of this review is to show an overview to know the main UT produced in end-stage renal disease patients, and how prebiotics and probiotics intervention acts as a helpful tool in CKD treatment.


Assuntos
Microbioma Gastrointestinal , Insuficiência Renal Crônica/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Prebióticos , Probióticos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Toxinas Biológicas/biossíntese , Uremia/complicações , Uremia/metabolismo
20.
BMC Neurosci ; 20(1): 52, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585527

RESUMO

BACKGROUND: Neurological complications may occur in patients with acute or chronic renal failure; however, in cases of acute renal failure, the signs and symptoms are usually more pronounced, and progressed rapidly. Oxidative stress and nitric oxide in the hippocampus, following kidney injury may be involved in cognitive impairment in patients with uremia. Although many women continue taking hormone therapy for menopausal symptom relief, but there are also some controversies about the efficacy of exogenous sex hormones, especially estrogen therapy alone, in postmenopausal women with kidney injury. Herein, to the best of our knowledge for the first time, spatial memory and synaptic plasticity at the CA1 synapse of a uremic ovariectomized rat model of menopause was characterized by estradiol replacement alone. RESULTS: While estradiol replacement in ovariectomized rats without uremia, promotes synaptic plasticity, it has an impairing effect on spatial memory through hippocampal oxidative stress under uremic conditions, with no change on synaptic plasticity. It seems that exogenous estradiol potentiated the deleterious effect of acute kidney injury (AKI) with increasing hippocampal oxidative stress. CONCLUSIONS: Although, estrogen may have some positive effects on cognitive function in healthy subjects, but its efficacy in menopause subjects under uremic states such as renal transplantation, needs to be further investigated in terms of dosage and duration.


Assuntos
Lesão Renal Aguda/fisiopatologia , Região CA1 Hipocampal/fisiopatologia , Estradiol/efeitos adversos , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Lesão Renal Aguda/complicações , Animais , Feminino , Menopausa/psicologia , Neurônios/fisiologia , Ovariectomia , Ratos , Memória Espacial/fisiologia , Uremia/complicações , Uremia/fisiopatologia
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