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1.
Blood Purif ; 52(4): 323-331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36889302

RESUMO

INTRODUCTION: Cardiovascular (CV) events are the major cause of morbidity and mortality associated with blood pressure (BP) in hemodialysis (HD) patients. BP varies significantly during HD treatment, and the dramatic variation in BP is a well-recognized risk factor for increased mortality. The development of an intelligent system capable of predicting BP profiles for real-time monitoring is important. Our aim was to build a web-based system to predict changes in systolic BP (SBP) during HD. METHODS: In this study, dialysis equipment connected to the Vital Info Portal gateway collected HD parameters that were linked to demographic data stored in the hospital information system. There were 3 types of patients: training, test, and new. A multiple linear regression model was built using the training group with SBP change as the dependent variable and dialysis parameters as the independent variables. We tested the model's performance on test and new patient groups using coverage rates with different thresholds. The model's performance was visualized using a web-based interactive system. RESULTS: A total of 542,424 BP records were used for model building. The accuracy was greater than 80% in the prediction error range of 15%, and 20 mm Hg of true SBP in the test and new patient groups for the model of SBP changes suggested the good performance of our prediction model. In the analysis of absolute SBP values (5, 10, 15, 20, and 25 mm Hg), the accuracy of the SBP prediction increased as the threshold value increased. DISCUSSION: This databae supported our prediction model in reducing the frequency of intradialytic SBP variability, which may help in clinical decision-making when a new patient receives HD treatment. Further investigations are needed to determine whether the introduction of the intelligent SBP prediction system decreases the incidence of CV events in HD patients.


Assuntos
Big Data , Diálise Renal , Humanos , Pressão Sanguínea , Diálise Renal/efeitos adversos , Fatores de Risco , Análise Multivariada
2.
J Ren Nutr ; 33(6): 731-739, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37120127

RESUMO

OBJECTIVE: Although unhealthy diets exacerbate nutritional and metabolic derangements in patients with end-stage kidney disease (ESKD), how therapeutic diets that possess a variety of different dietary strategies acutely modify diverse biochemical parameters related to cardiovascular disease remains underexplored. METHODS: Thirty-three adults with end-stage kidney disease undergoing thrice-weekly hemodialysis participated in a randomized crossover trial comparing a therapeutic diet with their usual diets for 7 days, separated by a 4-week washout period. The therapeutic diet was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. The primary outcome measure was the mean difference in the change-from-baseline intact fibroblast growth factor 23 (FGF23) level between the 2 diets. The other outcomes of interest included changes in mineral parameters, uremic toxins, and high-sensitivity C-reactive protein (hs-CRP) levels. RESULTS: Compared with the usual diet, the therapeutic diet lowered intact FGF23 levels (P = .001), decreased serum phosphate levels (P < .001), reduced intact parathyroid hormone (PTH) levels (P = .003), lowered C-terminal FGF23 levels (P = .03), increased serum calcium levels (P = .01), and tended to lower total indoxyl sulfate levels (P = .07) but had no significant effect on hs-CRP levels. Among these changes, reduction in serum phosphate level achieved in 2 days, modifications of intact PTH and calcium levels in 5 days, and reductions in intact and C-terminal FGF23 levels in 7 days of therapeutic diet intervention. CONCLUSION: Within the 1-week intervention period, the dialysis-specific therapeutic diet rapidly reversed mineral abnormalities and tended to decrease total indoxyl sulfate levels in patients undergoing hemodialysis but had no effect on inflammation. Future studies to assess the long-term effects of such therapeutic diets are recommended.


Assuntos
Cálcio , Falência Renal Crônica , Adulto , Humanos , Proteína C-Reativa , Estudos Cross-Over , Indicã , Fatores de Crescimento de Fibroblastos , Diálise Renal , Falência Renal Crônica/terapia , Hormônio Paratireóideo , Dieta , Fosfatos , Minerais
3.
J Clin Nurs ; 32(23-24): 8043-8053, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37668267

RESUMO

AIMS: To examine the relationship among eHealth literacy, empowerment and self-management and the mediating effects of empowerment in diabetic kidney disease (DKD) patients in the eHealthcare context. BACKGROUND: Self-management is an essential aspect of healthcare in delaying disease progression for DKD. In the eHealthcare era, health services providing self-management are transforming. The ability and confidence of patients to use eHealth services is a critical issue that impacts the effectiveness of self-management, but little is known about the role of eHealth literacy and empowerment in self-management. DESIGN: A cross-sectional study guided by the STROBE. METHODS: Overall, 127 Taiwanese patients were enrolled using convenience sampling. Data collection used structured questionnaires and chart reviews. Multiple regression was used to infer self-management predictors, and SPSS PROCESS macro and bootstrapping verified the mediating effects. RESULTS: Empowerment and eHealth literacy both showed significant positive correlations with self-management. Empowerment was the main predictor of self-management and had a complete mediating effect between eHealth literacy and self-management. CONCLUSION: Increasing patients' eHealth literacy can improve empowerment and prevent health inequality issues. Healthcare providers should consider improving patients' eHealth literacy to enhance their self-management. RELEVANCE TO CLINICAL PRACTICE: Healthcare service systems need to create user-friendly eHealthcare environments, and healthcare professionals can provide multifaceted instructions that fit patients' eHealth literacy levels to enhance their motivation and confidence in disease care, thus cultivating positive self-management behaviours. IMPACT: The popularity of eHealthcare services aimed at promoting self-management behaviours is increasing. However, the level of eHealth literacy is an essential factor that affects the effectiveness of self-management in the healthcare environment. In addition, empowerment is a major critical influence factor of self-management and a completely mediating variable between self-management and eHealth literacy. Consequently, healthcare providers should consider promoting patients' eHealth literacy to empower people using eHealthcare services for implementing self-management. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in cross-sectional studies (STROBE) checklist was used to ensure comprehensive reporting. PATIENT OR PUBLIC CONTRIBUTION: Patients were diagnosed with DKD in the study hospital. Physicians and case managers transferred patients to research assistants who screened them for the inclusion criteria and invited them to participate in this study if they met the requirements. After participants signed informed consent, the research nurse encouraged participants to respond to the research questionnaire face to face.


Assuntos
Letramento em Saúde , Autogestão , Telemedicina , Humanos , Estudos Transversais , Letramento em Saúde/métodos , Disparidades nos Níveis de Saúde , Inquéritos e Questionários , Telemedicina/métodos
4.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446114

RESUMO

Circulating uremic toxin indoxyl sulfate (IS), endothelial cell (EC) dysfunction, and decreased nitric oxide (NO) bioavailability are found in chronic kidney disease patients. NO nitrosylates/denitrosylates a specific protein's cysteine residue(s), forming S-nitrosothios (SNOs), and the decreased NO bioavailability could interfere with NO-mediated signaling events. We were interested in investigating the underlying mechanism(s) of the reduced NO and how it would regulate the S-nitrosylation of tissue transglutaminase (TG2) and its substrates on glycolytic, redox and inflammatory responses in normal and IS-induced EC injury. TG2, a therapeutic target for fibrosis, has a Ca2+-dependent transamidase (TGase) that is modulated by S-nitrosylation. We found IS increased oxidative stress, reduced NADPH and GSH levels, and uncoupled eNOS to generate NO. Immunoblot analysis demonstrated the upregulation of an angiotensin-converting enzyme (ACE) and significant downregulation of the beneficial ACE2 isoform that could contribute to oxidative stress in IS-induced injury. An in situ TGase assay demonstrated IS-activated TG2/TGase aminylated eNOS, NFkB, IkBα, PKM2, G6PD, GAPDH, and fibronectin (FN), leading to caspases activation. Except for FN, TGase substrates were all differentially S-nitrosylated either with or without IS but were denitrosylated in the presence of a specific, irreversible TG2/TGase inhibitor ZDON, suggesting ZDON-bound TG2 was not effectively transnitrosylating to TG2/TGase substrates. The data suggest novel roles of TG2 in the aminylation of its substrates and could also potentially function as a Cys-to-Cys S-nitrosylase to exert NO's bioactivity to its substrates and modulate glycolysis, redox, and inflammation in normal and IS-induced EC injury.


Assuntos
Indicã , Proteína 2 Glutamina gama-Glutamiltransferase , Humanos , Células Endoteliais , Estresse Oxidativo , Glicólise , Sulfatos
5.
Mol Biol Evol ; 38(10): 4149-4165, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-33170928

RESUMO

The Taiwanese people are composed of diverse indigenous populations and the Taiwanese Han. About 95% of the Taiwanese identify themselves as Taiwanese Han, but this may not be a homogeneous population because they migrated to the island from various regions of continental East Asia over a period of 400 years. Little is known about the underlying patterns of genetic ancestry, population admixture, and evolutionary adaptation in the Taiwanese Han people. Here, we analyzed the whole-genome single-nucleotide polymorphism genotyping data from 14,401 individuals of Taiwanese Han collected by the Taiwan Biobank and the whole-genome sequencing data for a subset of 772 people. We detected four major genetic ancestries with distinct geographic distributions (i.e., Northern, Southeastern, Japonic, and Island Southeast Asian ancestries) and signatures of population mixture contributing to the genomes of Taiwanese Han. We further scanned for signatures of positive natural selection that caused unusually long-range haplotypes and elevations of hitchhiked variants. As a result, we identified 16 candidate loci in which selection signals can be unambiguously localized at five single genes: CTNNA2, LRP1B, CSNK1G3, ASTN2, and NEO1. Statistical associations were examined in 16 metabolic-related traits to further elucidate the functional effects of each candidate gene. All five genes appear to have pleiotropic connections to various types of disease susceptibility and significant associations with at least one metabolic-related trait. Together, our results provide critical insights for understanding the evolutionary history and adaption of the Taiwanese Han population.


Assuntos
Povo Asiático , Genoma , Povo Asiático/genética , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
6.
J Formos Med Assoc ; 121 Suppl 1: S30-S38, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34980550

RESUMO

BACKGROUND/PURPOSE: The burden of end-stage kidney disease (ESKD) continues to grow globally. Information on medication prescribed to advanced chronic kidney disease (CKD) patients can help formulate further CKD prevention policies. This study aimed to review and assess several major medications routinely prescribed to pre-ESKD patients. METHODS: Medication information of advanced CKD patients one year before regular dialysis was collected from the National Health Insurance Research Database from 2000 to 2018 in Taiwan. Usages of major medication were comprehensively analyzed. RESULTS: During 2000-2018, trends in medication usage evolved gradually in the pre-ESKD population in Taiwan. The use of erythropoietin had increased (48.3% in 2000 to 71.0% in 2018) with decreased blood transfusion rate (70.9% in 2003 to 52.1% in 2018). The use of non-steroidal anti-inflammatory drugs had also dropped (43.5% in 2004 to 25.5% in 2018). These changes were more evident for patients enrolled in the pre-ESKD prevention program. The most frequently used blood pressure-lowering and glucose-lowering agents were calcium channel blockers (90.6%) and insulin (78.1%), but usage of metformin was unexpectedly high (38.4% in 2018). The most frequently used blood thinner was aspirin (49.5%), with considerably increased use of direct oral anticoagulant (16.5% in 2018). CONCLUSION: An overview of the trends of major medication usage and blood transfusion represented the continuously improving care quality in pre-ESKD patients in Taiwan. These trends were especially evident in patients enrolled in the pre-ESKD prevention program. This report also indirectly indicated the potential and long-term benefits of implementing CKD and pre-ESKD prevention programs.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Taiwan
7.
FASEB J ; 34(6): 8459-8474, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32362042

RESUMO

Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown. We screened 532 Taiwanese T1DM patients for CD biomarkers including anti-tissue transglutaminase (TGM2), anti-gliadin and anti-neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. We report that 3.76% of Taiwanese patients had TGM2-Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2-Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti-gliadin or anti-neoepitope Abs coexisted with ~3/4 of TGM2-Abs positive patients that were likely due to gluten-ingestion, while the cause of TGM2-Abs production for other ~1/4 of patients was unknown. Purified anti-TGM2 IgA (TGA) and anti-TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2's transamidation activity by up to 80% but TGG had no effects. Epitope mapping of all TGM2-Abs positive sera demonstrated that TGM2-Abs had heterogeneity in specificities. This is the first study on the differences between Taiwanese Han group and Caucasian in HLA genotypes and properties of TGM2-Abs.


Assuntos
Autoanticorpos/genética , Diabetes Mellitus Tipo 1/genética , Proteínas de Ligação ao GTP/genética , Antígenos HLA-DQ/genética , Transglutaminases/genética , Adolescente , Doença Celíaca/genética , Criança , Pré-Escolar , Células Endoteliais/metabolismo , Feminino , Genótipo , Gliadina/genética , Humanos , Imunoglobulina A/genética , Lactente , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Taiwan
8.
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
9.
Int J Mol Sci ; 21(18)2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932690

RESUMO

Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDNF) and serotonin were decreased in association with increased corticosterone and repressor element-1 silencing transcription factor (REST), regulators involved in neurological disorders. On the contrary, these PCS-induced changes were alleviated by uremic toxin absorbent AST-120. Taken together, PCS administration in mice with nephrectomy contributed to neurological disorders with increased oxidative stress and neuroinflammation, which were alleviated by PCS chelation. It is suggested that PCS may be a therapeutic target for chronic kidney disease-associated CNS diseases.


Assuntos
Cresóis/farmacologia , Inflamação/induzido quimicamente , Transtornos Mentais/induzido quimicamente , Doenças Neurodegenerativas/induzido quimicamente , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ésteres do Ácido Sulfúrico/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carbono/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Corticosterona/metabolismo , Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nefrectomia/métodos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurônios/metabolismo , Neurônios/patologia , Óxidos/farmacologia , Proteínas Repressoras/metabolismo , Serotonina/metabolismo , Toxinas Biológicas/farmacologia , Uremia/induzido quimicamente , Uremia/metabolismo , Uremia/patologia
10.
Kidney Blood Press Res ; 43(5): 1636-1645, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30380558

RESUMO

BACKGROUND/AIMS: Fabry disease (FD), a rare x-lined genetic disorder is a cause of renal deterioration. The phenotype of FD is highly variable and nonspecific, and correct diagnosis has always been delayed. We aimed to explore the prevalence and clinical presentation of FD in this high-risk male population in a Northern Taiwan medical center. METHODS: This is the first study to survey the incidence of FD in this high-risk population through the platform of a chronic kidney disease (CKD) education program in Asia. A total of 1,012 male patients with unknown CKD causes were screened using an assay of alpha-galactosidase A activity (α-Gal A) by dried blood spots (DBS). A final GLA gene analysis was also done for those with low enzyme activity. RESULTS: We identified two new patients with classic FD and four patients with late-onset FD. One novel GLA mutation with c.413 G>A was found in one classic FD patient (index 5). The prevalence of FD is about 0.59 % (6 in 1,012) in the high-risk population group with CKD. The clinical symptoms of FD patients are nonspecific except in those with various degrees of renal failure. Those patients' correct diagnosis was delayed, taking years and even decades. Three patients received enzyme replacement therapy and one started regular hemodialysis due to persistent renal function deterioration. Another two patients were found from family screening through a new index. In addition, a false negative result occurred in one patient who was proved to have FD by his kidney pathology as determined by this screening. CONCLUSION: FD is not such as rare a disease and its prevalence is greater in this high-risk male population. Clinicians need to be aware that FD should be included in the differential diagnosis in CKD with unknown etiology.


Assuntos
Doença de Fabry/diagnóstico , Falência Renal Crônica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Doença de Fabry/epidemiologia , Humanos , Isoenzimas/sangue , Isoenzimas/genética , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Insuficiência Renal Crônica , Taiwan , Adulto Jovem , alfa-Galactosidase/sangue , alfa-Galactosidase/genética
11.
Immun Ageing ; 15: 27, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30455721

RESUMO

BACKGROUND: Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. RESULTS: Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. CONCLUSIONS: Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.

12.
J Formos Med Assoc ; 117(10): 888-893, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29941330

RESUMO

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. METHODS: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good performance of our prediction models. We obtained similar results in validating via test data and data of newly enrolled patients (new-patient data), which is important for simulating prospective situations wherein dialysis staff are unfamiliar with new patients. This compensates for the retrospective nature of the BP records used in our study. CONCLUSION: The use of this validated intelligent system can identify patients who are at risk of IDH in advance, which may facilitate well-timed personalized management and intervention.


Assuntos
Monitores de Pressão Arterial , Hipotensão/diagnóstico , Diálise Renal/efeitos adversos , Idoso , Pressão Sanguínea , Bases de Dados Factuais , Feminino , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taiwan
14.
Amino Acids ; 49(3): 501-515, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27270573

RESUMO

Post-translational modification (PTM) is an important mechanism in modulating a protein's structure and can lead to substantial diversity in biological function. Compared to other forms of PTMs such as phosphorylation, acetylation and glycosylation, the physiological significance of aminylation is limited. Aminylation refers to the covalent incorporation of biogenic/polyamines into target protein by calcium-dependent transglutaminases (TGs). The development of novel and more sensitive techniques has led to more proteins identified as tissue transglutaminase (TG2) substrates and potential targets for aminylation. Many of these substrate proteins play a role in cell signaling, cytoskeleton organization, muscle contraction, and inflammation. TG2 is well studied and widely expressed in a variety of tissues and will be the primary focus of this review on recent advance in transglutaminase-mediated aminylation.


Assuntos
Aminas Biogênicas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Agregação Patológica de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Transglutaminases/metabolismo , Aminação , Animais , Aminas Biogênicas/química , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Proteínas de Ligação ao GTP/genética , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Agregação Patológica de Proteínas/genética , Domínios Proteicos , Proteína 2 Glutamina gama-Glutamiltransferase , Transdução de Sinais , Especificidade por Substrato , Transglutaminases/genética
15.
Kidney Blood Press Res ; 41(6): 1025-1036, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28006782

RESUMO

BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. RESULTS: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. CONCLUSIONS: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Indicã/efeitos adversos , Insuficiência Renal Crônica/patologia , Idoso , Células Cultivadas , Estudos Transversais , Técnicas de Diagnóstico Cardiovascular , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Indicã/sangue , Masculino , Pessoa de Meia-Idade
16.
Kidney Blood Press Res ; 40(2): 121-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25833743

RESUMO

BACKGROUND/AIMS: Advanced glycation end products (AGEs) are pro-inflammatory and pro-oxidative compounds that play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), inhibit endothelial function. We explored the association of IS and PCS with AGEs in a hemodialysis (HD) cohort. METHODS: This study was a cross-sectional study that recruited 129 stable patients on maintenance HD in a single medical center from July 1 to July 15, 2011. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. RESULTS: Serum levels of AGEs were associated with total IS (r = 2.7, p < 0.01) but not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) or free PCS (r = 0.04, NS) using Pearson's analysis. Multiple linear regression analysis showed that total IS was significantly related to AGEs (ß = 0.296, p < 0.01), free IS (ß = 0.502, p < 0.01) and creatinine (ß = 0.294, p < 0.01). Serum AGEs levels were also independently correlated with diabetes status (ß = 0.250, p = 0.01) and total IS (ß = 0.341, p < 0.01) concentrations after adjusting for other confounding variables. Moreover, patients with diabetes had higher serum AGEs levels than patients without diabetes (p < 0.01). CONCLUSIONS: These findings suggest that serum levels of total IS were associated with AGEs levels, which may participate in the process of atherosclerosis.


Assuntos
Cresóis/sangue , Produtos Finais de Glicação Avançada/metabolismo , Indicã/sangue , Diálise Renal , Ésteres do Ácido Sulfúrico/sangue , Idoso , Biomarcadores , Creatinina/sangue , Estudos Transversais , Nefropatias Diabéticas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urina , Resultado do Tratamento
18.
Artigo em Inglês | MEDLINE | ID: mdl-38934040

RESUMO

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI's pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-ß-D-glucosaminidase, tissue inhibitor of metalloprotease-2•insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.

19.
Catheter Cardiovasc Interv ; 82(3): E206-10, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23172759

RESUMO

The use of 5 or 6 Fr sheath in transradial (TR) approach is often required due to the relative small radial artery size. A sheathless approach may overcome the limitation of small radial size which limits the TR approach. Our case showed successful angioplasty of the right coronary artery chronic total occlusion (CTO) by bilateral TR approaches, utilizing a 7-Fr guide (7 Fr BL 3.5, 85 cm) for a retrograde sheathless approach, and a 6-Fr Ikari 3.5 guide catheter for an antegrade approach. The sheathless TR technique can minimize vascular trauma and increase back-up support for successful coronary intervention in CTO.


Assuntos
Angioplastia Coronária com Balão/métodos , Cateterismo Cardíaco/métodos , Oclusão Coronária/terapia , Artéria Radial , Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Doença Crônica , Angiografia Coronária , Oclusão Coronária/diagnóstico , Desenho de Equipamento , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Biomedicines ; 11(5)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37238983

RESUMO

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

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