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Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45â¯ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95â¯% confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127â¯mL/min/1.73â¯m2 (95â¯% CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.
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Retardadores de Chama , Organofosfatos , Insuficiência Renal Crônica , Humanos , Retardadores de Chama/toxicidade , Estudos Longitudinais , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/urina , Masculino , Feminino , Pessoa de Meia-Idade , Organofosfatos/toxicidade , Organofosfatos/urina , Idoso , Adulto , Rim/efeitos dos fármacos , Exposição Ambiental/estatística & dados numéricos , Compostos Organofosforados/urina , Compostos Organofosforados/toxicidade , Monitoramento Ambiental , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urinaRESUMO
Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.
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A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.
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Apoptose , Compostos Benzidrílicos , Cálcio , Glucose , Glucosídeos , Sistema de Sinalização das MAP Quinases , Mitocôndrias , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Glucose/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cálcio/metabolismo , Animais , Ratos , Linhagem Celular , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Caspase 3/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismoRESUMO
With an estimated prevalence of 1 in 1000 individuals globally, autosomal dominant polycystic kidney disease (ADPKD) stands as the most prevalent inherited renal disorder. Ultrasonography (US) is the most widely used imaging modality in the diagnosis and monitoring of ADPKD. This review discusses the role of US in the evaluation of ADPKD, including its diagnostic accuracy, limitations, and recent advances. An overview of the pathophysiology and clinical manifestations of ADPKD has also been provided. Furthermore, the potential of US as a noninvasive tool for the assessment of disease progression and treatment response is examined. Overall, US remains an essential tool for the management of ADPKD, and ongoing research efforts are aimed at improving its diagnostic and prognostic capabilities.
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Vascular calcification is commonly observed in chronic kidney disease (CKD) and is associated with increased morbidity and mortality. This study examined whether exogenous BMP7 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats. After an adenine diet for 4 weeks, the animals were injected with BMP7 for 2 weeks. Biochemical data, kidney tissue, bony structure, and vascular calcification of the thoracic aorta were examined and compared. Reduced renal function, hyperphosphatemia, and hyperparathyroidism with low 1,25(OH)2 vitamin D levels were observed in the adenine group. MicroCT revealed reduced bone mineral density (BMD), decreased bone and tissue volume ratio (BV/TV), and decreased trabecular number with increased separation. Marked vascular calcification was observed in adenine-fed animals, and immunohistochemical analysis showed increased expression of BMP2, RUNX2, vitamin D receptor (VDR), and Pit1 in aortic tissue. Treatment with BMP7 was associated with reduced serum phosphate, intact parathyroid hormone, FGF23, sclerostin, and DKK1 levels. BMP7 administration was accompanied with improvements in BMD and BV/TV. The increase in BMP2, RUNX2, VDR, and Pit1 was reversed by BMP7. In conclusion, exogenous BMP7 administration improved hyperphosphatemia and hyperparathyroidism in adenine-induced CKD. This treatment also attenuated vascular calcification and modulated structural abnormalities in the skeletal system.
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Hiperfosfatemia , Insuficiência Renal Crônica , Calcificação Vascular , Adenina , Animais , Proteína Morfogenética Óssea 7/uso terapêutico , Subunidade alfa 1 de Fator de Ligação ao Core , Hiperfosfatemia/complicações , Ratos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/metabolismoRESUMO
Tris(2-butoxyethyl) phosphate (TBEP) is one of the most abundant organophosphate flame retardants in the environment. This study aimed to evaluate the effect of TBEP exposure during adolescence on male reproductive function in adult rats. Male Sprague-Dawley rats were treated with 20 and 200 mg/kg body weight of TBEP or corn oil from postnatal day (PND) 42 to PND 105. A significant increase in the proportion of sperm with abnormal morphology (flattened head and bent tail) and superoxide anion (O2-.) production in the sperm of the 200 mg/kg treated group was observed (p < 0.05). Excessive production of sperm hydrogen peroxide (H2O2) was found in both the 20 and 200 mg/kg treatment groups (p < 0.05). Disruption of testicular structure was observed in the 20 and 200 mg/kg treated groups and seminiferous tubule degeneration was observed in the 200 mg/kg treated group. Our study demonstrated the adverse effects of TBEP on male reproductive function in rats.
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Retardadores de Chama , Fosfatos , Animais , Retardadores de Chama/toxicidade , Peróxido de Hidrogênio/farmacologia , Masculino , Organofosfatos/farmacologia , Compostos Organofosforados , Fosfatos/farmacologia , Ratos , Ratos Sprague-Dawley , Sêmen , EspermatozoidesRESUMO
The electronic whiteboard system is an important part of smart medical care. This system has been digitized and upgraded gradually over time, and now functions as a dashboard, incorporating sound effects, touch control, image display, face recognition, and other functions that maximize usage efficiency. In hospitals, electronic whiteboards are specialized for dedicated use in one of two areas: nursing stations and wards. Those used in nursing stations may upload data into the medical information system based on departmental and institutional requirements. Systems are built to the specific needs of different clinical departments and thus differ widely in terms of settings and functionality. Therefore, hospitals should promote regular communication among doctors, nurses, and patients.
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Hospitais , Médicos , Comunicação , Eletrônica , Humanos , TaiwanRESUMO
Disturbance in glucose and uric acid metabolism is the major disorder of metabolic syndrome (MetS). The kidneys play an important role in the management of glucose and uric acid. The aim of our study was to investigate alterations in renal glucose and uric acid transporters in animals with MetS after treatment with dapagliflozin and xanthine oxidase inhibitors (allopurinol and febuxostat). Sprague-Dawley rats were fed normal chow or a high fructose diet for the first 3 months. The fructose-fed animals were then treated with dapagliflozin, allopurinol, febuxostat, or no treatment for the next 3 months. Fasting glucose, insulin resistance, and hyperuricaemia were improved in all treatment groups except that in the fructose group (all p < 0.05). Both allopurinol and febuxostat reversed the increase in levels of sodium glucose cotransporter (SGLT) 1, SGLT2, and glucose transporter (GLUT) 2 (all p < 0.05). Dapagliflozin alleviated hyperuricaemia and induced uricosuria without affecting serum xanthine oxidase activity. Dapagliflozin suppressed the expression of GLUT9, urate transporter, and urate anion exchanger 1 (all p < 0.05), which was similar to the effects of allopurinol and febuxostat. The results suggest that treatment with dapagliflozin and xanthine oxidase inhibitors improved insulin resistance and reversed the increased expression of glucose and urate transporters in the kidney.
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Compostos Benzidrílicos , GlucosídeosRESUMO
PURPOSE: This study aimed to investigate the association between clinical factors and temporary changes in functional performance in patients undergoing hemodialysis. METHODS: This was a retrospective, longitudinal observational study conducted from 2015 to 2017. Eight-two patients undergoing hemodialysis in the outpatient clinic were enrolled. Functional performance was measured using the Karnofsky Performance Status (KPS) scale. Collected data for analysis included demographics, laboratory parameters, and KPS scale scores. All participants were grouped into a high KPS cluster and a low KPS cluster based on dynamic changes in KPS scales from 2015 to 2017. RESULTS: Participants in the high KPS cluster demonstrated an approximate trend, and those in the low KPS cluster demonstrated a low pattern. By stepwise selection model analysis, age (OR 1.12, 95% CI 1.03-1.23, p = 0.011), serum BUN (OR 1.08, 95% CI 1.02-1.16, p = 0.015), calcium levels (OR 3.24, 95% CI 1.2-8.73, p = 0.02), and beta-2-microglobulin (OR > 1.0, CI >1.00-<1.01, p = 0.031) showed risk for the low KPS cluster. Male sex (OR 0.20, 95% CI 0.04-0.96, p = 0.045) and albumin level (OR 0.02, 95% CI 0-0.4, p = 0.009) showed a low risk for the low KPS cluster. CONCLUSIONS: A different trajectory pattern was observed between the high and low KPS clusters in a 3-year period. Risk factors for the low KPS cluster were age, serum BUN, calcium, and beta-2-microglobulin levels. Male sex and serum albumin levels reduced the risk for the low KPS cluster.
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Avaliação de Estado de Karnofsky , Diálise Renal , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , TaiwanRESUMO
High serum levels of free fatty acids (FFAs) could contribute to obesity-induced nephropathy. CD36, a class B scavenger receptor, is a major receptor mediating FFA uptake in renal proximal tubular cells. Empagliflozin, a new anti-diabetic agent, is a specific inhibitor of sodium-glucose co-transporter 2 channels presented on renal proximal tubular cells and inhibits glucose reabsorption. In addition, empagliflozin has shown renoprotective effects. However, the mechanism through which empagliflozin regulates CD36 expression and attenuates FFA-induced lipotoxicity remains unclear. Herein, we aimed to elucidate the crosstalk between empagliflozin and CD36 in FFA-induced renal injury. C57BL/6 mice fed a high-fat diet (HFD) and palmitic acid-treated HK-2 renal tubular cells were used for in vivo and in vitro assessments. Empagliflozin attenuated HFD-induced body weight gain, insulin resistance, and inflammation in mice. In HFD-fed mice, CD36 was upregulated in the tubular area of the kidney, whereas empagliflozin attenuated CD36 expression. Furthermore, empagliflozin downregulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ. Treatment with a PPARγ inhibitor (GW9662) did not further decrease PPARγ expression, whereas a PPARγ antagonist reversed this effect; this suggested that empagliflozin may, at least partly, decrease CD36 by modulating PPARγ. In conclusion, empagliflozin can ameliorate FFA-induced renal tubular injury via the PPARγ/CD36 pathway.
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Compostos Benzidrílicos/administração & dosagem , Antígenos CD36/metabolismo , Ácidos Graxos não Esterificados/efeitos adversos , Glucosídeos/administração & dosagem , Túbulos Renais Proximais/citologia , PPAR gama/metabolismo , Substâncias Protetoras/administração & dosagem , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Animais , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Ácido Palmítico/farmacologia , Insuficiência Renal/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: To describe the associated factors for non-medical reasons for dropout in peritoneal dialysis (PD) patients. METHODS: A retrospective cohort study was performed using registry data of adult patients commencing PD as their initial renal replacement therapy in one hospital-facilitated PD center in Taiwan between 2014 and 2018. The collected data included socio-demographics and relevant medical and PD-related parameters. Kaplan-Meier analysis was used to determine the impact of non-medical reasons and medical reasons on PD dropout. RESULTS: The analysis included 224 PD patients, of whom 37 dropped out for non-medical reasons and 187 for medical reasons during the study period. There was significant difference between the two cohorts in age (62.3 years vs. 56.1 years, P = 0.010) and PD vintage (median 3.4 years vs. 4.8 years, P = 0.001). Diabetes was more predominant in the cohort for non-medical reasons than in the one for medical reasons (54.1% vs. 27.3% respectively, P = 0.001). In non-medical reason cohort, two leading reasons given for dropping out were lacking of caregivers (n = 12) and losing confidence (n = 10), whereas PD-related peritonitis (n = 101) was the main medical reason for PD dropout. Using Kaplan-Meier curve analysis, patients in the non-medical reason cohort demonstrated higher cumulative dropout rate compared to patients in the medical reason cohort during a 10-year period (P < 0.001). CONCLUSIONS: The main characteristics of PD dropout patients for non-medical reasons are age, diabetes, patients' perception and caregiver support.
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Atitude , Pacientes Desistentes do Tratamento/psicologia , Diálise Peritoneal/psicologia , Apoio Social , Adulto , Fatores Etários , Idoso , Cuidadores , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Percepção , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de TempoRESUMO
Purpose: In this prospective study, we aimed to examine the sociodemographic factors and clinical factors associated with psychological disorders in chronic kidney disease (CKD) patients receiving unplanned hemodialysis (HD).Methods: We prospectively enrolled 187 CKD stage 5 patients receiving unplanned HD at a tertiary hospital from January 2015 to December 2016. We used structured questionnaires to gather data about participants' anxiety, depression, and sleep disturbance. Generalized linear regression analysis was used to examine the relationships between sociodemographic and laboratory parameters, and severity of psychological distress.Results: The mean age of the participants was 60 years, and the number of men and women was 97 and 90, respectively. We did not find a significant association between anxiety, depression, and sleep disturbance scores and gender, age, marital status, religion status, education levels, and employment status and number of comorbidities. Generalized linear regression analysis showed that a multidisciplinary CKD care program in outpatient clinic disclosed a significant negative association with psychological disorders in participants.Conclusions: CKD patients exhibited psychological distress when receiving unplanned HD, not closely associated with sociodemographic profiles.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Falência Renal Crônica/complicações , Diálise Renal/psicologia , Transtornos do Sono-Vigília/epidemiologia , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Autorrelato , Índice de Gravidade de Doença , Taiwan/epidemiologiaRESUMO
Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-ß) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-ß and NF-κB levels.
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OBJECTIVE: To analyze the effects of chronic kidney disease (CKD) care programs on clinical outcomes. DESIGN: An observational, retrospective study with medical record review. SETTING: Kaohsiung Chang Gung Memorial Hospital. PARTICIPANTS: Patients diagnosed with CKD. INTERVENTIONS: CKD care programs conducted by nephrologists-based team from 2006 to 2013 in our hospital. MAIN OUTCOME MEASURES: We set 10 goals with treatment target ranges based on the guidelines suggested by the following organizations: Kidney Disease Improving Global Outcomes (2012) and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (2003). RESULTS: In total, 1486 patients were enrolled. Their average estimated glomerular filtration rate (ml/min/1.73 m2) was 31.9 at baseline and declined to 28.9 in Year 3 (P < 0.001). The all-goals attainment rate increased from 59.4% at baseline to 60.5% in Year 3, with an especially significant improvement for low-density lipoprotein (from 46.8% to 67.0%) and glycated hemoglobin (from 55.0% to 64.0%). Achievement rates decreased for hemoglobin (from 34.2% to 31.0%), calcium (from 94.6% to 92.3%) and phosphate (from 89.9% to 82.5%) between baseline and Year 3. Albuminuria was the least achieved goal (from 23.4% to 24.0%). Subgroup analysis revealed that estimated glomerular filtration rate did not decline in patients who had a good achievement rate, but decreased significantly in patients with a poor achievement rate. CONCLUSION: Enrolment in CKD care programs resulted in a significant improvement in goal attainment by patients. Further, a good achievement rate was associated with better preservation of residual renal function.
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Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/terapia , Idoso , Albuminúria , Cálcio/sangue , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , TaiwanRESUMO
High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1ß, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1ß, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1ß, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.
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Apoptose/efeitos dos fármacos , Antígenos CD36/metabolismo , Inflamassomos/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nefrite/induzido quimicamente , Obesidade/etiologia , Ácido Palmítico/toxicidade , Proteinúria/induzido quimicamente , Animais , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Antígenos CD36/antagonistas & inibidores , Linhagem Celular , Dieta Hiperlipídica , Modelos Animais de Doenças , Humanos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos Endogâmicos C57BL , Nefrite/metabolismo , Nefrite/patologia , Nefrite/prevenção & controle , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , Ácidos Oleicos/farmacologia , Proteinúria/metabolismo , Proteinúria/patologia , Proteinúria/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Succinimidas/farmacologiaRESUMO
BACKGROUND/AIMS: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. METHODS: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. RESULTS: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. CONCLUSION: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.
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Diálise Peritoneal , Potássio/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Humanos , Hiperpotassemia/sangue , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangueRESUMO
BACKGROUND/AIMS: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. METHODS: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. RESULTS: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. CONCLUSION: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.
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Fosfatase Alcalina/sangue , Falência Renal Crônica/mortalidade , Diálise Renal/mortalidade , Idoso , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , RiscoRESUMO
BACKGROUND: Vascular calcification (VC) is a key process associated with cardiovascular mortality in dialysis patients. Gelsolin is an actin-binding protein that can modulate inflammation, correlated inversely with hemodialysis (HD) mortality and involved in bone calcification homeostasis. In this report, we aim to characterize progression in aortic arch calcification (AAC) and investigate its association with gelsolin. METHODS: 184 HD patients were enrolled and their annual posterior-anterior chest X-ray films (CXR) in 2009 and 2013 were examined. The severity of AAC was classified as grade 0 to 3. Blood levels of gelsolin were measured by ELISA kits. Biographic and biochemical data at baseline were analyzed with status of AAC at baseline and changes after 4 years. RESULTS: At baseline, 60% of the patients had detectable AAC on CXR. After 4 years, 77% had AAC. Patients with grade 1 and 2 AAC had increased risk of progression (Odds ratio [OR] 2~3, P=0.001) compared to those with grade 0 at baseline. Compared to those with no AAC, patients with AAC progression had older age, lower gelsolin, higher waist circumference and prevalence of vascular disease. Regression analysis confirmed baseline gelsolin (odds ratio 0.845, 95% confidence interval [0.734-0.974]) and waist circumference as the independent factors associated with AAC progression. Gelsolin is positively correlated with serum albumin and negatively with tumor necrosis factor-alpha. CONCLUSION: Our study demonstrated that HD patients with grades 1 or 2 baseline AAC are at increased risk of further progression compared to those with grade 0. We also found lower blood levels of gelsolin associated with progressive AAC. Further investigation into the mechanistic roles of gelsolin in vascular calcification may provide new understanding of this key process.
Assuntos
Aorta Torácica/fisiopatologia , Gelsolina/sangue , Diálise Renal/efeitos adversos , Calcificação Vascular/etiologia , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Biomarcadores/sangue , Humanos , Pessoa de Meia-Idade , Radiografia Torácica , Calcificação Vascular/diagnóstico por imagemRESUMO
Protein-energy wasting (PEW) contributes to mortality in hemodialysis (HD) patients. Adipokines regulate energy homeostasis and body weight. Circulating gelsolin can modulate inflammation and is correlated with HD mortality. Whether adipokines and gelsolin play important roles in PEW remains unclear. Based on the criteria proposed by the International Society of Renal Nutrition and Metabolism, we examined the associations between PEW and biomarkers (gelsolin, leptin, adiponectin, interleukin-6, tumor necrosis factor alpha [TNF-α]) in 188 stable HD patients. Patients with PEW had significantly lower serum leptin levels, and tended to have higher adiponectin, TNF-α, and lower gelsolin levels. Logistic regression analysis revealed that gelsolin, leptin, adiponectin, and blood urea nitrogen were independently associated with PEW score. Serum creatinine, TNF-α, gender, renin-angiotensin system (RAS) blockade, and lipid-lowering agents were not associated with PEW score. Patients on lipid-lowering agents had lower PEW scores and those with RAS blockade had higher PEW scores. Our study confirms that gelsolin, adiponectin, and leptin are significant associates with PEW in HD patients. Further understanding of how these factors contribute to PEW may help design novel therapeutic strategies for PEW in chronic kidney disease.
Assuntos
Adipocinas/sangue , Gelsolina/sangue , Desnutrição Proteico-Calórica/sangue , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Desnutrição Proteico-Calórica/etiologia , Insuficiência Renal Crônica/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Indoxyl sulfate (IS) contributes to oxidative stress and endothelial dysfunction in chronic kidney disease patients. However, the role of mitochondria in IS-induced oxidative stress is not very clear. In this study, we examined whether mitochondria play a pivotal role in modulating the effects of antioxidants during IS treatment. In the context of human umbilical vein endothelial cells, we found that IS had a dose-dependent antiproliferative effect. In addition, we used flow cytometry to demonstrate that the level of reactive oxygen species increased in a dose-dependent manner after treatment with IS. High doses of IS also corresponded to increased mitochondrial depolarization and decreased mitochondrial DNA copy number and mitochondrial mass. However, these effects could be reversed by the addition of antioxidants, namely, vitamin C and N-acetylcysteine. Thus, our results suggest that IS-induced oxidative stress and antiproliferative effect can be attributed to mitochondrial dysfunction and impaired biogenesis and that these processes can be protected by treatment with antioxidants.