RESUMEN
Background and Objectives: Left ventricular hypertrophy (LVH) represents a significant cardiovascular risk in patients undergoing chronic hemodialysis (CHD). A large inferior vena cava diameter (IVCD), potentially indicative of fluid overload and a contributing factor to elevated cardiovascular risk, has not been sufficiently explored. Therefore, our study aims to gain further insights into this aspect. Materials and Methods: A retrospective cohort study enrolled patients receiving CHD in a single medical center with available echocardiography from October to December 2018. They were categorized into four groups based on LVH geometry and IVCD. Cox proportional hazard models assessed the risk of major adverse cardiovascular effects (MACEs) and cardiovascular and overall mortality after multivariate adjustments. Kaplan-Meier analysis depicted MACE-free events and survival during the follow-up time. Results: Of the 175 CHD patients, 38, 42, 45, and 50 exhibited small IVCD with eccentric and concentric LVH and large IVCD with eccentric and concentric LVH, respectively. Compared to small IVCD and eccentric LVH, large IVCD and eccentric LVH had the highest risk of MACEs, followed by large IVCD and concentric LVH (aHR: 4.40, 3.60; 95% CI: 1.58-12.23, 1.28-10.12, respectively). As for cardiovascular mortality, large IVCD and concentric LVH had the highest risk, followed by large IVCD and eccentric LVH, and small IVCD and concentric LVH. (aHR: 14.34, 10.23, 8.87; 95% CI: 1.99-103.35, 1.41-74.33; 1.01-77.87). The trend in overall mortality risk among the groups was similar to that of cardiovascular mortality. Conclusions: LVH geometry and IVCD co-modify the risk of MACEs and cardiovascular and overall mortality in CHD patients. The highest risk of MACEs is associated with large IVCD and eccentric LVH, while the highest risk of cardiovascular and overall mortality is linked with large IVCD and concentric LVH.
Asunto(s)
Enfermedades Cardiovasculares , Diálisis Renal , Vena Cava Inferior , Humanos , Masculino , Femenino , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Vena Cava Inferior/diagnóstico por imagen , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/complicaciones , Ecocardiografía/métodos , Factores de Riesgo , Modelos de Riesgos Proporcionales , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Estudios de Cohortes , Estimación de Kaplan-Meier , AdultoRESUMEN
BACKGROUND: Hemodialysis (HD) patients with peripheral arterial disease (PAD) are at heightened risk of adverse vascular events, and aspirin positively affects those outcomes. We aimed to investigate the association between different patterns of aspirin use and clinical vascular events in chronic HD patients with PAD. METHODS: This retrospective nationwide cohort study enrolled 758 chronic HD patients who had been diagnosed with PAD between January 1, 2008, and December 31, 2012, and followed up until the end of 2020. Patients were divided into three groups according to medication possession ratio (MPR) and continued use of aspirin (i.e., low MPR, high MPR but discontinuous prescription, and high MPR and continuous prescription). Percutaneous transluminal angioplasty (PTA), surgical bypass, lower leg amputation, cardiovascular events, cerebrovascular events, and all-cause mortality were evaluated. RESULTS: High MPR and continuous aspirin use had the lowest incidence of all-cause mortality and cardiovascular events compared with the two other groups, and it was significantly associated with low risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality (aHR: 0.58 [0.41-0.83], 0.49 [0.25-0.95], 0.57 [0.40-0.81], and 0.70 [0.55-0.88], respectively). Kaplan-Meier analysis revealed that event-free rates of PTA, cardiovascular events, and all-cause mortality of patients with high MPR and continuous aspirin treatment were the highest among the three groups (p < 0.05). CONCLUSION: Among HD patients with PAD, high MPR and continuous aspirin use significantly reduced the risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality and improved the event-free rates of PTA, cardiovascular events, and all-cause mortality during long-term follow-up.
Asunto(s)
Aspirina , Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Diálisis Renal , Humanos , Aspirina/uso terapéutico , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidadRESUMEN
Background: The factors affecting cardiovascular risk associated with vascular calcification in patients with chronic kidney disease are less well addressed. Distinct risk factors may contribute synergistically to this elevated cardiovascular risk in this population. Objectives: We aimed to determine whether echocardiographic left ventricular hypertrophy (LVH) affects the risk of major adverse cardiac events (MACE) associated with vascular calcification in end-stage kidney disease (ESKD) patients. Methods: In this retrospective cohort study, ESKD patients underwent chest radiography and echocardiography to assess aortic arch calcification (AoAC) and LVH, respectively, and were classified into three groups accordingly: non-to-mild AoAC without LVH, non-to-mild AoAC with LVH, and moderate-to-severe AoAC. The risks of MACE, cardiovascular mortality, and overall mortality were assessed using Cox proportional hazard analysis. Results: Of the 283 enrolled ESKD patients, 44 (15.5%) had non-to-mild AoAC without LVH, 117 (41.3%) had non-to-mild AoAC with LVH, and 122 (43.1%) had moderate-to-severe AoAC. After 34.1 months, 107 (37.8%) participants developed MACE, including 6 (13.6%), 40 (34.2%), and 61 (50%) from each respective group. Those with moderate-to-severe AoAC (Hazard ratio, 3.72; 95% confidence interval, 1.58-8.73) had a significantly higher risk of MACE than did those with non-to-mild AoAC without LVH or with non-to-mild AoAC and LVH (Hazard ratio, 2.73; 95% confidence interval, 1.16-6.46). A similar trend was observed for cardiovascular and overall mortality. Conclusion: Echocardiographic LVH could modify the risk of adverse cardiovascular events associated with vascular calcification in ESKD patients. Interventions aiming to ameliorate both morbidities might be translated into a lower MACE risk in this population.
RESUMEN
BACKGROUND: This study reports the outcomes of a collaborative program between dialysis clinics and a referral hospital, which consisted of clinical monitoring and supplementary routine surveillance, for improving the quality of vascular access care. METHODS: This retrospective observational study was performed at five dialysis clinics as part of a 2-year collaborative program (2019-2020) in conjunction with a hospital-based dialysis access management center. A total of 392 hemodialysis patients (arteriovenous fistula [AVF], n = 339 and arteriovenous graft [AVG], n = 53) were included. Outcome measures included the prognosis of vascular access, clinic satisfaction, and referral rate to the hospital. RESULTS: Increased vascular access flow was observed and critical flow events decreased from the first to the second year (AVF: 18.3% vs. 12.7%, p < 0.001; AVG: 26.2% vs. 20.1%, p = 0.30). There were fewer percutaneous transluminal angioplasty events in the AVG group (0.77 per person-year vs. 0.51 per person-year, p = 0.005). New AVF or AVG creation events also remained low. All dialysis clinics were satisfied with the program. The overall referral rate from the participating clinics increased (65.7% vs. 72.0%) during the study period independently of the physical distance between the dialysis clinic and the hospital. CONCLUSION: The collaboration between dialysis clinics and a referral hospital for improving the quality of vascular access care was successful in this study, and the model can be used by other clinics and hospitals looking to improve care coordination in dialysis patients.
RESUMEN
BACKGROUND: Arteriovenous fistula and arteriovenous graft are the most common types of vascular access for dialysis; stenosis and thrombosis are major complications leading to access failure and to an incresed risk of mortality. The aim of the present study was to assess the results of integrating strict vascular access blood flow surveillance with routine clinical monitoring for predicting vascular access stenosis in chronic hemodialysis patients. METHODS: In this retrospective study, chronic dialysis patients with arteriovenous fistula or arteriovenous graft were included from a setting in which all patients underwent quarterly blood flow surveillance in 2017. The results of blood flow surveillance were confirmed by thorough physical examination. Predictive performance of blood flow surveillance models in detecting stenosis in patients with arteriovenous fistula or arteriovenous graft was evaluated. The predictive performance of the quarterly blood flow surveillance model was described by confusion matrix. Differences in accuracy, positive predictive value (PPV), and negative predictive value (NPV) between blood flow surveillance models with distinct blood flow thresholds were evaluated. RESULTS: Of 397 included patients, 336 had an arteriovenous fistula and 61 had an arteriovenous graft. In 2017, 106 percutaneous transluminal angioplasty procedures were performed in patients with an arteriovenous fistula, and 63 in patients with an arteriovenous graft. The results revealed similar predictive performance of surveillance models using an absolute blood flow threshold of < 500 or < 400 mL/min in predicting stenosis in patients with arteriovenous fistula. Blood flow surveillance models for patients with an arteriovenous fistula had significantly higher accuracy than those for patients with an arteriovenous graft. Furthermore, the use of a relative threshold, defined as blood flow < 1000 mL/min and a 25% decline in blood flow, did not affect the predictive performance of blood flow surveillance models. CONCLUSION: Blood flow surveillance models using thresholds of < 400 and < 600 mL/min, followed by thorough physical examination, showed an accuracy of 91.54% and 72.15% in predicting stenosis in patients with arteriovenous fistula and arteriovenous graft, respectively. These two blood flow surveillance models may be integrated with routine clinical monitoring to improve early detection and treatment of stenosis in hemodialysis patients.
RESUMEN
AIM: Patients with end-stage kidney disease (ESKD) have an unparalleled risk of left ventricular hypertrophy (LVH) and vascular calcification (VC), both of which introduce excessive cardiovascular risk. However, it remains unclear whether LVH geometry co-modulates cardiovascular outcomes with VC in this population. METHODS: A retrospective cohort study was conducted. Patients with ESKD requiring chronic hemodialysis were identified from Shin Kong Wu Ho-Su Memorial Hospital between October and December 2018, with echocardiographic LVH geometry and aortic arch calcification (AoAC) determined. They were divided into four groups according to AoAC severity and eccentric or concentric LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyze their cardiovascular and all-cause mortality after multivariate adjustment. RESULTS: Overall, 223 patients with ESKD with LVH were analyzed, among whom 29.1%, 23.3%, 25.1%, and 22.4% had non-to-mild AoAC with eccentric and concentric LVH and moderate-to-severe AoAC with eccentric and concentric LVH, respectively. After 3.5 years of follow-up, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher risk of cardiovascular mortality than those with non-to-mild AoAC and eccentric LVH (hazard ratio 3.35, p=0.002). However, those with moderate-to-severe AoAC but eccentric LVH did not have higher cardiovascular mortality. Similarly, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher all-cause mortality than those with non-to-mild AoAC and eccentric LVH, whereas the other two groups did not have higher risk. CONCLUSION: LVH geometry could help stratify the risk of patients with ESKD when they had severe VC, and co-existing severe VC and concentric LVH aggravated cardiovascular risk.
Asunto(s)
Fallo Renal Crónico , Calcificación Vascular , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/epidemiología , Estudios Retrospectivos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Ventrículos Cardíacos , Calcificación Vascular/complicaciones , Remodelación VentricularRESUMEN
AIM: The aim of this study was to investigate the effects of continuous cilostazol use on emergency department (ED) visits, hospitalizations, and vascular outcomes in patients with hemodialysis (HD) with peripheral artery disease (PAD). METHODS: This retrospective cohort study recruited 558 adult patients, who had received chronic HD for at least 90 days between January 1, 2008 and December 31, 2012, from the National Health Insurance Research Database. Eligible patients were divided into two groups based on continuing or discontinuing cilostazol treatment. Outcome measures were ED visits, hospitalizations, mortality, and vascular outcomes such as percutaneous transluminal angioplasty, surgical bypass, lower leg amputation, ischemic stroke, hemorrhagic stroke, and cardiovascular events. RESULTS: Patients with continuous cilostazol use had significantly higher prevalence of stroke, cancer, vintage, and the use of angiotensin receptor blocker and ß-blocker, but significantly lower incidence of ischemic stroke and cardiovascular events, as well as lower mortality, than those without continuous cilostazol use (all pï¼.05). Continuous cilostazol use was independently associated with lower risk of ED visits, hemorrhagic stroke, and cardiovascular events (adjusted hazard ratios: 0.79, 0.29, and 0.67; 95% confidence intervals: 0.62-0.98, 0.10-0.84, and 0.48-0.96, respectively; all pï¼.05). Continuous cilostazol use was significantly associated with higher ED visit-free and cardiovascular event-free rates (log-rank test; pï¼.05). CONCLUSION: Continuous treatment of cilostazol in patients with HD with PAD significantly decreases the risk of ED visits, hemorrhagic stroke, and cardiovascular events and improves ED visit-free and cardiovascular event-free rates during long-term follow-up.
Asunto(s)
Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Humanos , Cilostazol , Accidente Cerebrovascular Hemorrágico/inducido químicamente , Accidente Cerebrovascular Hemorrágico/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Diálisis Renal , Estudios Retrospectivos , Resultado del Tratamiento , AdultoRESUMEN
Introduction: This study aimed to investigate the association of aortic arch calcification (AoAC) and aortic valve calcification (AVC) with major adverse cardiovascular events (MACE) and cardiovascular and all-cause mortality in patients on maintenance hemodialysis (MHD). Methods: This study enrolled 297 adult patients with end-stage kidney disease who were on MHD. They were divided into those with an AoAC score <2 without AVC (n = 70, 23.6%), those with an AoAC score <2 with AVC (n = 96, 32.3%), and those with an AoAC score ≥2 regardless of AVC status (n = 131, 44.1%). We analyzed the risks of MACE, cardiovascular and overall mortality among the three groups using Cox proportional hazard analyses. Survival probabilities were estimated using the log-rank test via the Kaplan-Meier method. Results: Kaplan-Meier analysis revealed that the MACE-free rate and the survival rates of cardiovascular and overall mortality were significantly higher in adult chronic hemodialysis patients with AoAC score <2 without AVC, followed by those with AoAC score <2 with AVC, and then those with AoAC score ≥2 (log-rank test; all p < 0.01). The grade of AoAC is a significant risk factor for MACE, cardiovascular mortality, and overall mortality after adjusting for age and gender Relative to AoAC score <2 without AVC, adult chronic hemodialysis patients with AoAC score ≥2 remained an independently significantly risk factor of MACE (adjusted hazard ratio, 2.17; 95% confidence interval 1.11-4.20; p = 0.023) after adjusting for age, sex, and all significant variables in baseline characteristics. Conclusion: AoAC grade was positively correlated with a higher risk of MACE and cardiovascular and overall mortality. Furthermore, the presence of AVC modified the adverse cardiovascular risk associated with AoAC in patients on MHD.
RESUMEN
Background: Little is known about the association of inferior vena cava diameter (IVCD) and left ventricular end-systolic diameter (LVESD) with mortality in patients undergoing hemodialysis (HD). Methods: The single medical center observational cohort study enrolled 241 adult chronic HD patients from 1 October 2018 to 31 December 2018. Echocardiography results of IVCD and LVESD prior to dialysis were retrieved and patients were divided into high IVCD and low IVCD groups. Patients who received HD via a tunneled cuffed catheter were excluded. Study outcomes included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Subgroup analyses of HD patients with high and low LVESD were also performed. Results: The incidence of all-cause mortality, cardiovascular mortality, and MACE were higher in chronic HD patients with high IVCD (p < 0.01). High IVCD patients had significantly greater all-cause mortality, cardiovascular mortality, and MACE (log-rank test; p < 0.05). High IVCD patients are also associated with an increased risk of all-cause mortality and MACE relative to low IVCD patients (aHRs, 2.88 and 3.42; 95% CIs, 1.06−7.86 and 1.73−6.77, respectively; all p < 0.05). In the subgroup analysis of patients with high or low LVESD, the high IVCD remained a significant risk factor for all-cause mortality and MACE, and the HR is especially high in the high LVESD group. Conclusions: Dilated IVCD is a risk factor for all-cause mortality and MACE in chronic HD patients. In addition, these patients with high LVESD also have a significantly higher HR of all-cause mortality and MACE.
RESUMEN
Background: A clinically tunneled cuffed catheter (TCC) for hemodialysis (HD) is often inserted into end-stage renal disease patients, who have an immature or no arteriovenous fistula (AVF), for the performance of HD to relieve uremic syndrome or to solve uncontrolled fluid overload, hyperkalemia, or metabolic acidosis. The catheter is primarily regarded as a bridge until the AVF matures and can be cannulated for HD. However, the effect of the bridge of the TCC on the future patency of AVFs remains elusive. Methods: This nationwide population-based observational study compared the hazards of AVF failure and the time to AVF failure. We enrolled 24,142 adult incident patients on HD, who received HD via AVFs for at least 90 days between 1 January 2010 and 31 December 2015. The subjects were divided into two groups, according to the history of TCC, and were followed-up until the failure of the AVF, mortality, or the end of the study. A propensity score-matched analysis based on 1:1 matching of age, sex, and baseline comorbidities was utilized to reduce bias and confounding variables. Results: A Kaplan−Meier survival curve revealed that patients with and without a history of TCC had significantly better AVF survival rates (log-rank test; p < 0.001). A history of TCC was independently associated with a higher risk of new AVF or AVG creation due to AVF failure, after the adjustment of the Charlson comorbidity index score (corresponding adjusted hazard ratios of 2.17 and 1.52; 95% confidence intervals of 1.77−2.67 and 1.15−1.99). For the impact of time on AVF failure, patients with a TCC bridge had a significantly higher incidence of new AVF creation during the first year after the AVF cannulation. Conclusion: A history of a TCC bridge was an independent risk factor for AVF failure and the time of AVF failure was significantly higher during the first year after the fistula cannulation in the TCC bridge group.
RESUMEN
OBJECTIVES: Maintenance of vascular access (VA) patency after percutaneous transluminal angioplasty (PTA) is important and remains a challenge despite VA monitoring and surveillance. The aim of this study was to examine factors affecting the post-PTA arteriovenous access (AVA) patency in patients who have been on close VA monitoring and surveillance for access flow. DESIGN: Retrospective cohort study. SETTING: A single medical centre in Taiwan. PARTICIPANTS: Records of patients who received chronic haemodialysis between 1 January 2017 and 31 December 2018 were retrospectively reviewed. Patients were divided into two groups (without or with PTA intervention on AVA). PRIMARY AND SECONDARY OUTCOME: Patients were followed until reintervention PTA, termination or abandoned VA or end of study. In addition to routine monitoring, VA flow surveillance was performed every 3 months for detection of VA dysfunction adhering to Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: A total of 508 patients were selected for study inclusion (with PTA, n=231; without PTA, n=277). At baseline, variables that differed between groups included malignancy and levels of albumin, uric acid, potassium, phosphorous, high-density lipoprotein, total bilirubin and ferritin (all p<0.05). Significant between-group differences were observed for ß-adrenergic blocking agents (with PTA, 49.8%; without PTA, 37.5%; p, 0.007) and ADP inhibitors (with PTA, 23.8%; without PTA, 11.2%; p<0.001). Among patients with PTA, those with acute myocardial infarction, high ferritin level or arteriovenous graft (AVG) had a significantly higher risk of reintervention post-PTA (p<0.05). Dipeptidyl peptidase-4 inhibitors, thiazolidinediones, ADP inhibitors, and warfarin use were predictors of post-PTA patency (p<0.05). CONCLUSIONS: AVG access type, acute myocardial infarction, and high ferritin levels are risk factors for re-intervention post-PTA. These findings may be useful in the development of prophylactic strategies for monitoring VA function and tailoring surveillance programs for these dialysis patients.
Asunto(s)
Angioplastia de Balón , Derivación Arteriovenosa Quirúrgica , Angioplastia , Oclusión de Injerto Vascular/etiología , Humanos , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Dermatologic disease is a neglected public health challenge that disproportionately affects resource-poor settings. Globally, dermatologic disease contributes the fourth highest burden of nonfatal disability with the most acute impact in the Oceanic region, including the Republic of Palau. Efforts to address the dermatologic health inequality are hindered without the necessary epidemiologic evidence to guide health policy in the resource-poor setting of Palau. METHODS: We conducted a 4-year cross-sectional study of all Dermatology Service patients in the Belau National Hospital and outreach community health centers from 2015 to 2018. No other specialized dermatology service was available. Skin disease was classified by both diagnosis and Global Burden of Disease criteria and analyzed by age, gender, region, and surrounding Oceanic nations. RESULTS: The study enrolled 494 patients comprising 179 males and 315 females between 2015 and 2018. The most prevalent diseases were eczema (48.8%), superficial fungal infection (24.5%), and pruritus (22.7%). The neglected tropical disease of scabies was detected in four patients. Males were significantly more likely to present with cellulitis, keratinocyte carcinoma, stasis dermatitis, wounds, marine-related dermatitis, viral skin disease, tinea faciei, verruca, and xerosis and females with melasma and hyperpigmentation. CONCLUSION: This study presents the first primary epidemiologic data describing the prevalence of dermatologic disease in the Palauan adult population. The significant burden of disease in Palau compared with other Oceanic nations validates ongoing dermatology services and informs public health implications for resource allocation and disease management to achieve health equality in the resource-poor nation.
Asunto(s)
Eccema , Enfermedades de la Piel , Adulto , Servicios de Salud Comunitaria , Estudios Transversales , Eccema/epidemiología , Femenino , Disparidades en el Estado de Salud , Humanos , Masculino , Palau/epidemiología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/epidemiologíaRESUMEN
TRPA1, a nonselective cation channel, is expressed in sensory afferent that innervates peripheral targets. Neuronal TRPA1 can promote tissue repair, remove harmful stimuli and induce protective responses via the release of neuropeptides after the activation of the channel by chemical, exogenous, or endogenous irritants in the injured tissue. However, chronic inflammation after repeated noxious stimuli may result in the development of several diseases. In addition to sensory neurons, TRPA1, activated by inflammatory agents from some non-neuronal cells in the injured area or disease, might promote or protect disease progression. Therefore, TRPA1 works as a molecular sentinel of tissue damage or as an inflammation gatekeeper. Most kidney damage cases are associated with inflammation. In this review, we summarised the role of TRPA1 in neurogenic or non-neurogenic inflammation and in kidney disease, especially the non-neuronal TRPA1. In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate hypoxia-reoxygenation injury in vitro and ischaemia-reperfusion-induced kidney injury in vivo through MAPKs/NF-kB signalling. Acute kidney injury (AKI) patients with high renal tubular TRPA1 expression had low complete renal function recovery. In renal disease, TPRA1 plays different roles in different cell types accordingly. These findings depict the important role of TRPA1 and warrant further investigation.
Asunto(s)
Enfermedades Renales/metabolismo , Canal Catiónico TRPA1/metabolismo , Animales , Humanos , Inflamación/metabolismo , Enfermedades Renales/patología , Neuronas/metabolismo , Transducción de SeñalRESUMEN
Oxidative stress and inflammation play important roles in the pathophysiology of acute kidney injury (AKI). Transient receptor potential ankyrin 1 (TRPA1) is a Ca2+-permeable ion channel that is sensitive to reactive oxygen species (ROS). The role of TRPA1 in AKI remains unclear. In this study, we used human and animal studies to assess the role of renal TRPA1 in AKI and to explore the regulatory mechanism of renal TRPA1 in inflammation via in vitro experiments. TRPA1 expression increased in the renal tubular epithelia of patients with AKI. The severity of tubular injury correlated well with tubular TRPA1 or 8-hydroxy-2'-deoxyguanosine expression. In an animal model, renal ischemia-reperfusion injury (IR) increased tubular TRPA1 expression in wild-type (WT) mice. Trpa1-/- mice displayed less IR-induced tubular injury, oxidative stress, inflammation, and dysfunction in kidneys compared with WT mice. In the in vitro model, TRPA1 expression increased in renal tubular cells under hypoxia-reoxygenation injury (H/R) conditions. We demonstrated that H/R evoked a ROS-dependent TRPA1 activation, which elevated intracellular Ca2+ level, increased NADPH oxidase activity, activated MAPK/NF-κB signaling, and increased IL-8. Renal tubular TRPA1 may serve as an oxidative stress sensor and a crucial regulator in the activation of signaling pathways and promote the subsequent transcriptional regulation of IL-8. These actions might be evident in mice with IR or patients with AKI.
Asunto(s)
Lesión Renal Aguda/metabolismo , Desoxiguanosina/metabolismo , Túbulos Renales/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/genética , Daño por Reperfusión/metabolismo , Canal Catiónico TRPA1/metabolismo , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/genética , Adulto , Animales , Calcio/metabolismo , Línea Celular , Desoxiguanosina/análogos & derivados , Modelos Animales de Enfermedad , Epitelio/metabolismo , Epitelio/patología , Humanos , Inmunohistoquímica , Interleucina-8/metabolismo , Túbulos Renales/citología , Túbulos Renales/enzimología , Túbulos Renales/patología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , NADP/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canal Catiónico TRPA1/genéticaRESUMEN
OBJECTIVES: To investigate the effect of the Early Chronic Kidney Disease (CKD) Care Programme on CKD progression in patients with CKD stage I-IIIa. DESIGN: Observational cohort study. SETTING: Taipei Medical University Research Database from three affiliated hospitals. PARTICIPANTS: Adult non-pregnant patients with CKD stage I-IIIa from Taipei Medical University Research Database between 1 January 2012 and 31 August 2017 were recruited. These patients were divided into Early CKD Care Programme participants (case) and non-participants (control). The models were matched by age, sex, estimated glomerular filtration rate and CKD stage with 1:2 propensity score to reduce bias between two groups. OUTCOME MEASURES: The risks of CKD stage I-IIIa progression to IIIb between Early CKD Care Programme participants and non-participants. RESULTS: Compared with the control group, the case group demonstrated more comorbidities and higher proportions of hypertension, diabetes mellitus, gout, dyslipidaemia, heart disease and cerebrovascular disease, but had lower risk of progression to CKD stage IIIb before and (HR 0.72; 95% CI 0.61 to 0.85) and after (adjusted HR (aHR) 0.67; 95% CI 0.55 to 0.81) adjustments. Moreover, Kaplan-Meier analysis revealed the cumulative incidence of CKD stage IIIb was significantly lower in the case group than in the control group. Finally, the programme was an independent protective factor against progression to stage IIIb, especially in patients with CKD stage IIIa before (HR 0.72; 95% CI 0.61 to 0.85) and after (aHR 0.67; 95% CI 0.55 to 0.81) adjustments. CONCLUSIONS: The Early CKD Care Programme is an independent protective factor against progression of early CKD.
Asunto(s)
Insuficiencia Renal Crónica , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Humanos , Riñón , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: Central venous occlusive disease is a critical complication in long-term hemodialysis patients with arteriovenous (AV) dialysis circuits. The purpose of this retrospective, single-arm cohort study was to evaluate the effectiveness of an abdominal aortic aneurysm (AAA) contralateral leg endoprosthesis to treat symptomatic central venous occlusive diseases in patients with chronic hemodialysis. METHODS: A prospective cohort study included 60 patients on hemodialysis presenting with central venous stenosis or occlusion, who were treated with a Gore Excluder AAA contralateral leg stent graft between December 2013 and July 2018. Follow-up angiography was obtained at 3, 6, and 12 months. The outcomes and duration of primary circuit and target site patency were measured from the time of the stent graft implantation to the first reintervention for AV circuit dysfunction and target site restenosis. Secondary patency was calculated from stent graft implantation to the point when AV access was no longer attainable. RESULTS: Circuit primary patency rate was 54.9% at 1 year of Gore Excluder AAA contralateral leg or iliac extender stent grafts, implanted in 60 hemodialysis patients with central vein occlusive disease. Cumulative target site primary patency rate was 88.3% at 1 year. Secondary patency rate was 95% during follow-up. Patients with concomitant lesions had a significantly higher risk of circuit primary patency dysfunction. CONCLUSIONS: Treatment of central vein obstructions in hemodialysis patients with stent grafts has been appealing owing to the tapered shape with a larger diameter and the availability of various lengths.
Asunto(s)
Derivación Arteriovenosa Quirúrgica , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Procedimientos Endovasculares/instrumentación , Diálisis Renal , Enfermedades Vasculares/cirugía , Venas/cirugía , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Constricción Patológica , Procedimientos Endovasculares/efectos adversos , Femenino , Oclusión de Injerto Vascular/etiología , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/fisiopatologíaRESUMEN
OBJECTIVES: A common cause of hemodialysis vascular access dysfunction, a primary cause of morbidity and mortality in patients undergoing hemodialysis, is central venous stenosis or occlusion. The present study compared percutaneous transluminal angioplasty (PTA) with percutaneous transluminal angioplasty and stent placement (PTS) for treatment of central venous stenosis or central vein occlusion in hemodialysis patients. METHODS: A systematic literature review was conducted using database searches of PubMed, Cochrane, and Embase. Articles were selected using the Population/Intervention/Comparator/Outcomes (PICO) process. Outcomes included the rate of procedural success, primary patency, assisted primary patency, re-intervention subjects, re-intervention rate, and adverse events. RESULTS: A total of eight studies were included in the meta-analysis with subjects in the PTA group (n = 281) or PTS group (n = 192). Primary patency rate between PTA and PTS groups at 3-, 6-, 12-, or 24-month follow-up was not different (all p > 0.05). Patients treated with PTA had greater assisted primary patency rates than the PTS group (OR = 1.03, 1.73, 1.03, and 2.00 at 3, 6, 12, and 24 months, respectively). However, the statistical assessment only showed significantly at 24-month follow-up (p = 0.01). CONCLUSIONS: The present meta-analysis revealed that, compared to PTS, PTA may provide increased assisted primary patency for endovascular treatment of central vein stenosis or occlusion in patients undergoing hemodialysis. LEVEL OF EVIDENCE: Level 3a.
Asunto(s)
Angioplastia/métodos , Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal/métodos , Stents , Enfermedades Vasculares/terapia , Anciano , Constricción Patológica/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Grado de Desobstrucción Vascular , VenasRESUMEN
BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. METHODS: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan-Meier curves and logistic regression analysis. RESULTS: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35-37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26-37.27; p = 0.03). CONCLUSION: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.
RESUMEN
In this study we immobilized gold nanoparticles (AuNPs) onto thiol-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films as bioelectronic interfaces (BEIs) to be integrated into organic electrochemical transistors (OECTs) for effective detection of dopamine (DA) and also as surface-enhanced Raman scattering (SERS)-active substrates for the selective detection of p-cresol (PC) in the presence of multiple interferers. This novel PEDOT-based BEI device platform combined (i) an underlying layer of polystyrenesulfonate-doped PEDOT (PEDOT:PSS), which greatly enhanced the transconductance and sensitivity of OECTs for electrochemical sensing of DA in the presence of other ascorbic acid and uric acid metabolites, as well as amperometric response toward DA with a detection limit (S/N = 3) of 37 nM in the linear range from 50 nM to 100 µM; with (ii) a top interfacial layer of AuNP-immobilized three-dimensional (3D) thiol-functionalized PEDOT, which not only improved the performance of OECTs for detecting DA, due to the signal amplification effect of the AuNPs with high catalytic activity, but also enabled downstream analysis (SERS detection) of PC on the same chip. We demonstrate that PEDOT-based 3D OECT devices decorated with a high-density of AuNPs can display new versatility for the design of next-generation biosensors for point-of-care diagnostics.
RESUMEN
Given advancements in cancer immunity, cancer treatment has gained breakthrough developments. Immune checkpoint inhibitors, such as programmed cell death 1 (PD-1) inhibitors, are the most promising drugs in the field and have been approved to treat various types of cancer, such as metastatic melanoma, head and neck squamous cell carcinoma, and urothelial carcinoma. However, whether PD-1 inhibitors should be administered to renal transplant patients with advanced cancer remains unclear because the T-cells produced after administration of these inhibitors act against not only tumor antigens but also donor alloantigens. Thus, the use of PD-1 inhibitors in kidney-transplanted patients with advanced cancer is limited on account of the high risk of graft failure due to acute rejection. Hence, finding optimal treatment regimens to enhance the tumor-specific T-cell response and decrease T-cell-mediated alloreactivity after administration of a PD-1 inhibitor is necessary. Thus far, no recommendations for the use of PD-1 inhibitors to treat cancer in renal transplant patients are yet available, and very few cases reporting kidney-transplanted patients treated with PD-1 inhibitors are available in the literature. Therefore, in this work, we review the published cases and suggest feasible approaches for renal transplant patients with advanced malignancy treated by a PD-1 inhibitor. Of the 22 cases we obtained, four patients maintained intact grafts without tumor progression after treatment with a PD-1 inhibitor. Among these patients, one maintained steroid dose before initiation of anti-PD1, two received immunosuppressive regimens with low-dose steroid and calcineurin inhibitor (CNI)-elimination with sirolimus before initiation of anti-PD-1 therapy, and one received combined anti-PD-1, anti-vascular endothelial growth factor (VEGF), and chemotherapy with unchanged immunosuppressive regimens. mammalian target of rapamycin (mTOR) inhibitors and anti-VEGF may act as regulators of tumor-specific and allogenic T-cells. However, more studies are necessary to explore the optimal therapy and ensure the safety and efficacy of PD-1 inhibitors in kidney-transplanted patients.