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Gota , Humanos , Gota/genética , Monocitos , Brote de los Síntomas , Perfilación de la Expresión GénicaRESUMEN
Gout commonly manifests as a painful, self-limiting inflammatory arthritis. Nevertheless, the understanding of the inflammatory and immune responses underlying gout flares and remission remains ambiguous. Here, based on single-cell RNA-Seq and an independent validation cohort, we identified the potential mechanism of gout flare, which likely involves the upregulation of HLA-DQA1+ nonclassical monocytes and is related to antigen processing and presentation. Furthermore, Tregs also play an essential role in the suppressive capacity during gout remission. Cell communication analysis suggested the existence of altered crosstalk between monocytes and other T cell types, such as Tregs. Moreover, we observed the systemic upregulation of inflammatory and cytokine genes, primarily in classical monocytes, during gout flares. All monocyte subtypes showed increased arachidonic acid metabolic activity along with upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2). We also detected a decrease in blood arachidonic acid and an increase in leukotriene B4 levels during gout flares. In summary, our study illustrates the distinctive immune cell responses and systemic inflammation patterns that characterize the transition from gout flares to remission, and it suggests that blood monocyte subtypes and Tregs are potential intervention targets for preventing recurrent gout attacks and progression.
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Gota , Humanos , Gota/genética , Gota/metabolismo , Monocitos/metabolismo , Ácido Araquidónico , Brote de los Síntomas , Perfilación de la Expresión GénicaRESUMEN
Introduction: Researchers have investigated the causal effect between serum uric acid (SUA) concentrations and kidney function for decades, but studies produced inconsistent results. This study aimed to clarify the bidirectional causal effects between SUA concentrations and kidney function and to explore the potential ethnic disparities by conducting a trans-ethnic Mendelian randomization study in European, African, and Asian ancestries. Materials and methods: The summary-level data for this study were obtained from the Global Urate Genetics Consortium, CKDGen Consortium, UK Biobank, and Japan Biobank for different outcomes and exposures, respectively. The traits of kidney function were estimated glomerular filtration rate from serum creatinine (eGFRcr), estimated glomerular filtration rate from cystatin C (eGFRcys), and blood urea nitrogen (BUN). Using the multiplicative random-effects inverse variance weighting mode, our primary analysis produced robust results despite heterogeneity. Additionally, we performed the Mendelian randomization pleiotropy residual sum and outlier test to eliminate the horizontal pleiotropy and obtain accurate results. Results: Our findings revealed that elevated SUA concentrations had causal effects on declined eGFRcys, BUN, and a diagnosis of chronic kidney disease in European ancestries and eGFRcr in Asian ancestries. Additionally, the causal effects of declined eGFRcr and elevated BUN concentrations on elevated SUA concentrations were observed in both European and Asian ancestries. However, no bidirectional causal effect was found between SUA concentrations and eGFRcr among African ancestries. Conclusions: This trans-ethnic Mendelian randomization study confirmed the bidirectional causal effects between SUA concentrations and kidney function and highlighted the importance of considering ethnic disparities in clinical treatments.
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As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increased HLA-DQA1high classic monocytes and PTGS2high monocytes in advanced gout and overactivated CD8+ T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.
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Gota , Leucocitos Mononucleares , Humanos , Leucocitos Mononucleares/metabolismo , Ácido Úrico/metabolismo , Gota/genética , Gota/metabolismo , Inflamación/metabolismo , Monocitos/metabolismo , Enfermedad CrónicaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a severe public health problem associated with a disordered gut microbiome. However, the functional alterations of microbiota and their cross talk with metabolism pathways based on disease severity remain unclear. RESULTS: We performed metagenomics and untargeted metabolomics in a cohort of 68 patients with CKD of differing severities and 20 healthy controls to characterize the complex interplay between the gut microbiome and fecal and serum metabolites during CKD progression. We identified 26 microbial species that significantly changed in patients with CKD; 18 species changed as the disease progressed, and eight species changed only in a specific CKD group. These distinct changes in gut microbiota were accompanied by functional alterations in arginine and proline, arachidonic acid, and glutathione metabolism and ubiquinone and other terpenoid-quinone biosynthesis pathways during CKD progression. Further metabolomic analyses revealed that the distributions of toxic and pro-oxidant metabolites from these four essential metabolic pathways varied in the feces and serum as CKD progressed. Furthermore, we observed a complex co-occurrence between CKD severity-related bacteria and the characterized metabolites from the four essential metabolic pathways. Notably, Ruminococcus bromii, fecal hydroquinone, and serum creatinine were identified as the main contributors to the integrated network, indicating their key roles in CKD progression. Moreover, a noninvasive model including R. bromii and fecal hydroquinone, L-cystine, and 12-keto-tetrahydro-LTB4 levels classified the CKD severity (area under the curve [AUC]: > 0.9) and had better performance than the serum creatinine level for mild CKD (AUC: 0.972 vs. 0.896). CONCLUSIONS: Perturbed CKD severity-related gut microbiota may contribute to unbalanced toxic and pro-oxidant metabolism in the gut and host, accelerating CKD progression, which may be an early diagnostic and therapeutic target for CKD. Video Abstract.
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Microbioma Gastrointestinal , Insuficiencia Renal Crónica , Humanos , Hidroquinonas , Creatinina , Especies Reactivas de Oxígeno , Metaboloma , Heces/microbiología , Metabolómica , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/microbiologíaRESUMEN
BACKGROUND: Gout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls. METHODS: We established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8). RESULTS: Eleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process. CONCLUSIONS: Histone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process. TRIAL REGISTRATION: This study is not a clinical trial.
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BACKGROUND: The global reputation of coronavirus disease (COVID-19) has led universities in China to conduct online teaching. However, the actual feedback from medical teachers and students regarding online education remains unclear. METHODS: A prospective questionnaire survey examined the current opinions of online education from teachers and students at the Medical School of Tongji University. RESULTS: A total of 488 valid questionnaires were collected (223 males, 45.7%; 265 females, 54.3%), including 394 students (80.7%) and 94 teachers (19.3%). Most teachers and students were "in favor of online teaching," had "positive views for online education," were "satisfied with online teaching," and "expected for regular online education," although students thought that "too much learning tasks had been assigned" (90.4% teachers vs. 43.1% students, P < 0.001) and "less teaching effect than in offline classes" (68.1% teachers vs. 43.4% students). Compared to female counterpart, male students had higher "learning interest" (27.6% vs. 14.9%), "learning attention" (29.2% vs. 14.4%), "learning efficiency" (30.2% vs. 16.7%), and "better learning effect" (27.6% vs. 15.3%). Furthermore, male students had a significantly rise in attendance rate. Compared with male teachers, female teachers had less "experience in online educational course recording" (25.9% vs. 50%) and "past training for online teaching" (53.7% vs. 77.5%). Furthermore, they tended to be more "resistant to online teaching" (44.4% vs. 22.5%) and less "ready for online teaching" (70.4% vs. 87.5%). There was no significant difference in the acceptance of online teaching among teachers in different age groups. CONCLUSIONS: Most teachers and students supported and were satisfied with the implementation of online education during the pandemic. Although teachers were less adaptable to online education, they still had positive opinions. Sex influenced the acceptance of online teaching. Male teachers and students showed better adaptability than their female counterparts. Although online teaching has advantages, it still cannot completely replace traditional offline teaching. As online education is a trend for future learning, universities should make more efforts to improve it, especially to provide more attention to female teachers and students.
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COVID-19 , Educación a Distancia , Estudiantes de Medicina , Estudios Transversales , Femenino , Humanos , Masculino , Pandemias , Estudios Prospectivos , SARS-CoV-2 , Facultades de Medicina , UniversidadesRESUMEN
AIM: We aimed to investigate the relationship between intact parathyroid hormone (iPTH) levels and all-cause death, cardiovascular events, and ectopic calcification in patients with diabetic kidney disease (DKD). METHODS: In this retrospective cohort study, we collected the clinical data of 508 patients with clinically diagnosed DKD. The primary and secondary outcomes were all-cause death or cardiovascular events and ectopic calcification, respectively. We used different regression methods to analyze the relationship between various clinical parameters and the two clinical outcomes. RESULTS: We found that iPTH was a risk factor for all-cause death and cardiovascular events (hazards ration [HR]: 2.817, 95% confidence interval [CI]: 1.045-6.562, P = 0.016). Meanwhile, diabetes duration (HR: 1.090, 95% CI: 1.045-1.138, P < 0.0001), triglycerides (TG) (HR: 1.254, 95% CI: 1.049-1.499, P = 0.013), and iPTH (HR: 1.954, 95% CI: 1.001-3.813, P = 0.049) were independent risk factors for ectopic calcification. In contrast to patients with lower iPTH levels (iPTH < 31.7 pg/mL), patients with higher iPTH levels (iPTH ≥ 31.7 pg/mL) had increased ectopic calcification rate (P = 0.002) and decreased survival time (P < 0.001). CONCLUSION: In patients with DKD, higher iPTH levels were significantly related to worsen clinical outcomes.
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Enfermedades Cardiovasculares , Nefropatías Diabéticas , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Nefropatías Diabéticas/epidemiología , Humanos , Hormona Paratiroidea , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Hemodialysis (HD) patients often develop chronic inflammation, which is associated with an increased risk of cardiovascular complications and mortality. Axl and its ligand, growth arrest 6 (Gas6), have been reported to play key roles in regulating the immune response. However, the function of Axl in HD patients has not been clarified. METHODS: In the present study, we enrolled 130 HD patients and 117 normal controls (NCs) and evaluated the levels of inflammatory markers, soluble Axl (sAxl), membrane Axl (mAxl), and Gas6 in all participants. The potential downstream cascades of Gas6-Axl signaling in HD patients were identified by quantitative real time polymerase chain reaction and western blotting. RESULTS: The levels of inflammatory cytokines-tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-plasma sAxl, and Gas6, were significantly increased in HD patients compared to NCs. Additionally, sAxl was positively associated with the inflammatory factor, interleukin-6 (IL-6), in HD patients. Moreover, we found that mAxl in CD14+ mononuclear cells and CD19+ B cells was increased upon HD. Furthermore, we discovered that the metalloproteinase ADAM17, also called TACE, contributed to the cleavage of mAxl into sAxl, and not ADAM10, in the peripheral blood mononuclear cells (PBMCs) of HD patients. The upregulation of Gas6-mAxl signaling caused the activation of the STAT1-SOCS3 pathway in the PBMCs of HD patients. After two years follow-up, patients with lower sAxl levels had longer survival time than those with higher sAxl levels. CONCLUSION: Our results suggest that Axl may play a significant role in systemic inflammation in HD patients.
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Inflamación/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/sangre , Proteínas Tirosina Quinasas Receptoras/metabolismo , Diálisis Renal/efectos adversos , Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Adulto , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Linfocitos B/metabolismo , Femenino , Humanos , Inflamación/genética , Inflamación/inmunología , Péptidos y Proteínas de Señalización Intercelular/sangre , Interferón gamma/sangre , Interleucina-6/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Tirosina Quinasas Receptoras/genética , Factor de Transcripción STAT1/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Tirosina Quinasa del Receptor AxlRESUMEN
Feasible and accurate predictors are urgently needed to evaluate the survival for patients with paraquat poisoning since the high mortality of paraquat poisoning always resulted in the loss of both life and money. Multiple predictors have been developed to predict prognosis of the patients with PQ poisoning, which however heavily depend on the time of admission to hospitals. Here we reported a feasible and accurate prognosis predictor for patients with paraquat poisoning that is independent of the time of admission to hospitals. Patients with paraquat poisoning were enrolled in this study according to the inclusion and exclusion criteria, which were grouped into survivors and non-survivors based on the 90-days follow-up investigation. The concentration of paraquat in serum and urine, and the baseline clinical parameters associated with the injuries of the liver, kidney, and lung were evaluated to predict the survival of these patients by using receiver operating characteristic curve (ROC) analysis, univariate and multivariate cox regression analyses. A total of 114 patients was included in this study with a survival rate of 54.4%. The median survival days of non-survivors were 6.0 (95%Cl: 4.0-7.8). A new predictor, namely paraquat concentration-associated multiorgan injury index (PCAMII), was established by integrating serum and urine paraquat concentration, serum creatinine, alanine aminotransferase, aspartate transaminase, total and direct bilirubin, at different weighting coefficients, with the accuracy of about 90%. The model to predict the survival probability by PCAMII was established with good fitness (R2 = 0.9325), providing the simulated survival rates comparable to the clinical data. PCAMII, which is independent of hospital admission time, is a feasible and accurate marker to predict the survival rate of patients with PQ poisoning.
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Paraquat , Humanos , Pronóstico , Curva ROC , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUD AND PURPOSE: Hyperphosphatemia, which is a high inorganic phosphate (Pi) level in the serum, promotes endothelial cells dysfunction and is associated with cardiovascular diseases in patients with chronic kidney diseases (CKD). However, the underlying mechanism of high Pi-induced endothelia cell apoptosis remains unclear. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with normal Pi (1.0 mM) and high Pi (3.0 mM), and then cell apoptosis, abnormal gene expression and potential signaling pathway involvement in simulated hyperphosphatemia were examined using flow cytometry, quantitative PCR (qPCR) and western blot analysis. A two-step 5/6 nephrectomy was carried out to induce CKD and biochemical measurements were taken. RESULTS: The rat model of CKD revealed that hyperphosphatemia is correlated with an increased death-domain associated protein (DAXX) expression in endothelial cells. In vitro, high Pi increased the mRNA and protein expression level of DAXX in HUVECs, effects that were reversed by additional phosphonoformic acid treatment. Functionally, high Pi resulted in a significantly increased apoptosis in HUVECs, whereas DAXX knockdown markedly repressed high Pi-induced cell apoptosis, indicating that DAXX mediated high Pi-induced endothelial cell apoptosis. High Pi treatment and DAXX overexpression induced the activation of extracellular regulated protein kinases (ERKs), while DAXX knockdown inhibited high Pi-induced ERKs activation. Finally, we demonstrated that DAXX overexpression induced HUVECs apoptosis in the presence of normal Pi, whereas additional treatment with U0126 (a specific ERK inhibitor) reversed that effect. CONCLUSION: Upregulated DAXX promoted high Pi-induced HUVECs apoptosis by activating ERK signaling and indicated that the DAXX/ERK signaling axis may be served as a potential target for CKD therapy.
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Autophagy has been demonstrated to be vital for kidney homeostasis and is centrally implicated in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin-induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin-induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule-associated protein 1A/1B-light chain 3 (LC3)BII/I expression and autophagosome formation. Consistently, in cisplatin-injured renal tubular cells in vitro, lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK-α phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy-related molecules, like mammalian target of rapamycin and LC3BII/I. AMPK-α activation is likely required for lithium-induced tubular cell autophagy and protection in cisplatin-induced AKI because blockade of AMPK-α phosphorylation by compound C markedly abrogated lithium-induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin-induced AKI by enhancing autophagy via AMPK-α activation.-Bao, H., Zhang, Q., Liu, X., Song, Y., Li, X., Wang, Z., Li, C., Peng, A., Gong, R. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.
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Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Adenilato Quinasa/metabolismo , Autofagia/efectos de los fármacos , Cisplatino/toxicidad , Litio/farmacología , Adenilato Quinasa/genética , Animales , Células Epiteliales/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Túbulos Renales Proximales/citología , Masculino , Ratones , Fosforilación/efectos de los fármacosRESUMEN
Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC-MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, L-isoleucine, L-lysine, and L-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that L-isoleucine, L-lysine, and L-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout.
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Aminoácidos/sangre , Gota/sangre , Hiperuricemia/sangre , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos BiológicosRESUMEN
It is known that inflammation and oxidative stress have strong influences on chronic kidney disease (CKD). As an antioxidant, bilirubin is currently under extensive scrutiny. However, there are disagreements with regard to the oxidative and antioxidative roles of serum uric acid (SUA). This study aimed to investigate the relationship between serum bilirubin and the progression of renal function in CKD patients with hyperuricemia (HUA). This retrospective longitudinal study included 427 CKD patients. The endpoint was renal replacement therapy or death. Patients were divided into the following two groups according to the SUA level: HUA group (SUAâ¯≥â¯420⯵mol/L for men; SUAâ¯≥â¯360⯵mol/L for women) and normal uric acid level (NUA) group. A Cox proportional hazards model was used to evaluate the risk factors for renal outcomes in the two patient groups. The median follow-up time was 36â¯months. In the Cox regression analysis, the risk of renal outcomes in patients with serum indirect bilirubin (IBIL) levels >4.55⯵mol/L was 0.15 times the risk in patients with serum IBIL levels ≤4.55⯵mol/L (hazard ratioâ¯=â¯0.15, pâ¯=â¯.013). Our findings suggest that a high serum IBIL level might be a protective factor for the progression of renal function in CKD patients with HUA.
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Bilirrubina/sangre , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Hiperuricemia/patología , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/patología , Estudios Retrospectivos , Ácido Úrico/sangreRESUMEN
BACKGROUND: To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2. METHODS: This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20-60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses. RESULTS: Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis. When compared to baseline, serum uric acid (SUA) decreased significantly after treatment in both groups, but no differences were detected among all the follow-up points. After 12-month treatment, eGFR did not have significant change in both groups. In the benzbromarone group, kidney stones in one case increased in quantity. In the febuxostat group, kidney stones in one case became smaller in size and in two cases vanished completely. Both drugs did not increase myocardial enzymes significantly after the treatment. In addition, hemoglobin increased significantly in the two groups (p < 0.05). CONCLUSIONS: Benzbromarone and febuxostat could reduce SUA and maintain renal function in chronic kidney disease (CKD) patients with eGFR 20-60 mL/min/1.73 m2. Urate-lowering therapy with benzbromarone or febuxostat could increase serum hemoglobin level and potentially improve anemia.
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Benzbromarona/uso terapéutico , Febuxostat/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Uricosúricos/uso terapéutico , Anciano , alfa-Globulinas/orina , Benzbromarona/efectos adversos , Febuxostat/efectos adversos , Femenino , Tasa de Filtración Glomerular , Hemoglobinas/metabolismo , Humanos , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Cálculos Renales/inducido químicamente , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Ácido Úrico/sangre , Ácido Úrico/orinaRESUMEN
BACKGROUND: Oxidative stress and inflammation play pivotal roles in chronic kidney disease (CKD). Bilirubin is an endogenous anti-inflammatory antioxidant. However, the relationship between serum bilirubin and renal outcomes in CKD is controversial. We explored the association of serum bilirubin levels with renal outcomes in Han Chinese patients with CKD. METHODS: Clinical and laboratory data were collected from 316 patients with CKD. The primary clinical endpoint was renal replacement therapy or death. The association between serum bilirubin and clinical parameters was assessed by correlation analysis. Multiple Cox regression analysis was used to explore the relationship between serum bilirubin and renal outcomes in patients with CKD. RESULTS: Serum total and indirect bilirubin were positively correlated with estimated glomerular filtration rate, but negatively correlated with 24-h urine protein in patients with CKD. Serum total and indirect bilirubin were inversely associated with CKD stages in patients with CKD stages 1-5. Multiple Cox regression analysis demonstrated that the higher concentration of serum total bilirubin was independently associated with better renal outcomes in CKD. CONCLUSIONS: Our results suggest that serum total bilirubin may have protective effects on kidneys.
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Bilirrubina/sangre , Insuficiencia Renal Crónica/sangre , China , Técnicas de Laboratorio Clínico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/diagnóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To investigate whether combined continuous venovenous hemofiltration and hemoperfusion among paraquat-poisoned patients would improve survival. DESIGN: Prospective, controlled interventional study over 4 years. SETTING: Single, tertiary, academic medical center. PATIENTS: We recruited patients admitted to Shanghai Tenth People's Hospital within 48 hours after paraquat ingestion. Exclusions were under 14 years old, ingestion of paraquat with other toxicants, pregnant, a history of chronic pulmonary disease, psychosis, hyperthyroidism, or diabetes with impaired liver or renal function. INTERVENTIONS: All patients were assigned to receive continuous venovenous hemofiltration with hemoperfusion therapy (continuous venovenous hemofiltration group) and to receive conventional therapy (conventional group). The study outcomes were death from any cause within 90 days after paraquat ingestion and the frequencies of hypoxia, acute kidney injury, or adverse events. MEASUREMENTS AND MAIN RESULTS: Of the 110 enrolled patients, 59 were assigned to continuous venovenous hemofiltration group and 51 to conventional group. The two groups had similar baseline demographics and clinical features. At 90 days after paraquat ingestion, 19 of 59 patients (32.2%) in the continuous venovenous hemofiltration group and 29 of 51 patients (56.9%) in the conventional group had died (hazard ratio, 0.43; 95% CI, 0.24-0.76; p = 0.004). In multivariable Cox proportional hazard models controlling for baseline characteristics, combined continuous venovenous hemofiltration and hemoperfusion was independently associated with reduced risk of death compared with conventional therapy (adjusted hazard ratio, 0.35; 95% CI, 0.19-0.64; p = 0.001). Patients in the continuous venovenous hemofiltration group, as compared to the conventional group, had a reduced occurrence rate of hypoxia (40.7% vs 72.5%; p = 0.001) and of acute kidney injury (59.3% vs 78.4%; p = 0.03). Hypophosphatemia and thrombocytopenia were more common in the continuous venovenous hemofiltration group (p < 0.05). CONCLUSIONS: In patients with paraquat poisoning, treatment with combined continuous venovenous hemofiltration and hemoperfusion significantly improved 90-day survival rates.
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Cuidados Críticos/métodos , Hemofiltración , Hemoperfusión , Paraquat/envenenamiento , Lesión Renal Aguda/mortalidad , Adulto , Causas de Muerte , Terapia Combinada , Femenino , Lavado Gástrico , Hemofiltración/efectos adversos , Hemoperfusión/efectos adversos , Humanos , Hipofosfatemia/mortalidad , Hipoxia/mortalidad , Masculino , Estudios Prospectivos , Análisis de Supervivencia , Trombocitopenia/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method. MATERIALS AND METHODS: 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. RESULTS: Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05). CONCLUSION: Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.
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Medios de Contraste/administración & dosificación , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico por imagen , Ácido Úrico/sangre , Nefropatías Diabéticas/fisiopatología , Femenino , Humanos , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Riesgo , UltrasonografíaRESUMEN
PURPOSE: To investigate the diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease (DKD). MATERIALS AND METHODS: 55 DKD patients with estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2) and 26 normal controls (NCs) were enrolled. Clinical data was well documented. Blood samples were drawn for evaluation of renal function including blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA), and urine samples were assayed for total protein quantification, and various microprotein markers. According to eGFR level, DKD patients were divided into early-stage DKD (eGFR ≥90 ml/min/1.73 m(2), n = 18) and middle-stage DKD (eGFR 30-90 ml/min/1.73 m(2), n = 37). Based on urinary microalbumin/creatinine ratio (MALB/UCR), early-stage DKD patients were further classified into two groups: MALB/UCR <10 g/mol (n = 11) and MALB/UCR ≥10 g/mol (n = 7). Then, CEUS was performed to observe the real-time renal perfusion, and low acoustic power contrast-specific imaging was used for quantitative analysis. RESULTS: The renal perfusion images of CEUS were well developed successively. The corresponding perfusion curves based on echo-power signals in time series were constructed. Quantitative analysis showed that area under the descending curve (AUC2) was significantly increased in early-stage DKD compared to middle-stage DKD (p < 0.05), but AUC showed no significant difference. Further comparison between different MALB/UCR levels of early-stage DKD showed that patients with MALB/UCR ≥10 g/mol had significantly increased levels of AUC, AUC2 and proteinuria than patients with low MALB/UCR (p < 0.05). Also, high MALB/UCR DKD patients had increased proteinuria but similar eGFR compared to low MALB/UCR patients. CONCLUSION: Renal microvascular hyperperfusion may be responsible for overt proteinuria until decline of renal filtration in DKD. AUC2 could be an early and sensitive marker for early renal injury and renal microvascular hyperperfusion in DKD.
Asunto(s)
Nefropatías Diabéticas/diagnóstico por imagen , Riñón/irrigación sanguínea , Circulación Renal , Anciano , Albuminuria/orina , Área Bajo la Curva , Estudios de Casos y Controles , Medios de Contraste , Creatinina/orina , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/diagnóstico por imagen , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Fosfolípidos , Índice de Severidad de la Enfermedad , Hexafluoruro de Azufre , UltrasonografíaRESUMEN
AIMS: Paraquat Poisoning (PQ) can cause illness and death, and its main causes of mortality are acute respiratory failure and lung fibrosis. Early recognition of this condition and early treatment are vital. Thus, it is of importance to target the key genes controlling pathogenesis in the early stage of PQ. MAIN METHODS: C57BL/6 mice were used for Paraquat intragastric administration as a model of PQ. Following a gene chip-based screening, the change of gene expression in the lung was further validated by bioinformatic analyses, co-expression network construction and real-time RT-PCR, Western blot and immunofluorescence assays. KEY FINDINGS: 2287 genes with differential expression were identified at the very early stage of PQ. From these, 76 genes that were linked to mitochondrion function were further pursued. Among these genes, PSTK was a phosphorylase kinase which serves a protective role in oxidative stress lung damage. PSTK was the central gene in a 30-gene network that is important for mitochondrial complex I assembly, mitochondrial apoptosis and mitochondrial fatty acid beta-oxidation, suggesting that they could conceivably be related to the pathogenesis of PQ induced lung damage. Lastly, we confirmed that PSTK was lowered in rodent lungs following PQ. SIGNIFICANCE: PSTK emerges as a central gene in a network of mitochondrial function genes in PQ exposed mice. The functional role of PSTK in PQ induced lung injury warrants further examination.