RESUMEN

Background: Disturbances in the cardiovascular system, bone and skeletal muscle are independent risk factors for death among patients receiving haemodialysis (HD). However, the combined impact of disorders of these three organs on morbidity and mortality is unclear in the HD population. Methods: A total of 3031 Japanese patients on maintenance HD were prospectively followed. The outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and bone fracture. Patients were divided into four groups (G1-G4) according to the baseline number of diseased organs represented as histories of cardiovascular disease and bone fractures and the presence of low skeletal muscle mass as follows: G1, no organ; G2, one organ; G3, two organs; G4, three organs. Multivariable-adjusted survival models were used to analyse associations between the number of diseased organs and outcomes. Results: During a 4-year follow-up, 499 deaths, 540 MACE and 140 bone fractures occurred. In the Cox proportional hazards model, the risk for all-cause mortality was significantly higher in G2, G3 and G4 than in G1 as the reference {hazard ratio: G2, 2.16 [95% confidence interval (CI) 1.65-2.84], G3, 3.10 [95% CI 2.27-4.23] and G4, 3.11 [95% CI 1.89-5.14]}. Similarly, the risks for developing MACE and bone fractures were significantly elevated as the number of organ disorders increased. Conclusions: Multiple disorders of the cardiovascular-bone-skeletal muscle axis are strong predictors of morbidity and mortality in patients undergoing HD.

RESUMEN

Acute kidney injury (AKI) is a complex clinical syndrome with a rapid decrease in renal function caused by several different etiologies, including sepsis, ischemia, and the administration of nephrotoxic drugs. Tubular arginase 2 (ARG2), an arginine-metabolic enzyme, is a potential therapeutic target for AKI, but it has not been confirmed under various AKI conditions. The aim of this study was to investigate ARG2 as a therapeutic target for cisplatin-induced AKI. Cisplatin-treated mice with a genetic deficiency in Arg2 had significant amelioration of renal dysfunction, characterized by decreased acute tubular damage and apoptosis. In contrast, cisplatin-induced tubular toxicity was not ameliorated in proximal tubule cells derived from Arg2-deficient mice. Immunohistochemical analysis demonstrated the increased infiltration of ARG2-positive macrophages in kidneys damaged by cisplatin. Importantly, cisplatin-treated Arg2 knockout mice exhibited a significant reduction in kidney inflammation, characterized by the decreased infiltration of inflammatory macrophages and reduced gene expression of interleukin (IL)-6 and IL-1ß. The secretion of IL-6 and IL-1ß induced by lipopolysaccharides was decreased in bone marrow-derived macrophages isolated from Arg2-deficient mice. Furthermore, the lipopolysaccharide-induced elevation of mitochondrial membrane potential and production of reactive oxygen species were reduced in bone marrow-derived macrophages lacking Arg2. These findings indicate that ARG2 promotes the inflammatory responses of macrophages through mitochondrial reactive oxygen species, resulting in the exacerbation of AKI. Therefore, targeting ARG2 in macrophages may constitute a promising therapeutic approach for AKI.

Asunto(s)

Lesión Renal Aguda , Cisplatino , Animales , Ratones , Lesión Renal Aguda/metabolismo , Arginasa/genética , Arginasa/metabolismo , Cisplatino/toxicidad , Riñón/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

INTRODUCTION: Cancer constitutes a major source of morbidity and mortality among people undergoing hemodialysis (HD). A systemic inflammatory response is associated with the incidence and prognosis of cancer in the general population. However, the effect of systemic inflammation on cancer-related mortality in patients undergoing HD remains unclear. METHODS: We analyzed 3,139 patients registered in the Q-Cohort Study, which is a multicenter, observational cohort study of patients on hemodialysis in Japan. The primary outcome was cancer-related mortality during a 10-year follow-up. The covariate of interest was serum C-reactive protein (CRP) concentrations at baseline. The patients were divided into tertiles based on their serum CRP concentrations at baseline (tertile [T] 1: ≤0.07; T2: 0.08-0.24; and T3: ≥0.25). The association between serum CRP concentrations and cancer-related mortality was calculated using the Cox proportional hazards model and the Fine-Gray subdistribution hazards model with non-cancer-related death as a competing risk. RESULTS: During the 10-year follow-up, 216 patients died of cancer. In the multivariable analysis, the risk of cancer-related mortality in the highest tertile (T3) of serum CRP concentrations was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval]: 1.68 [1.15-2.44]). This association remained consistent in the competing risk model, in which the subdistribution hazard ratio was 1.47 and the 95% confidence interval was 1.00-2.14 for T3 compared with T1. CONCLUSION: Higher serum CRP concentrations are associated with an increased risk of cancer-related mortality in patients undergoing maintenance HD.

Asunto(s)

Proteína C-Reactiva , Neoplasias , Humanos , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Biomarcadores , Medición de Riesgo , Diálisis Renal/efectos adversos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Neoplasias/complicaciones , Neoplasias/terapia

RESUMEN

The nervous and immune systems control whole-body homeostasis and respond to various types of tissue injury, including stroke, in a coordinated manner. Cerebral ischaemia and subsequent neuronal cell death activate resident or infiltrating immune cells, which trigger neuroinflammation that affects functional prognosis after stroke. Inflammatory immune cells exacerbate ischaemic neuronal injury after the onset of brain ischaemia; however, some of the immune cells thereafter change their function to neural repair. The recovery processes after ischaemic brain injury require additional and close interactions between the nervous and immune systems through various mechanisms. Thus, the brain controls its own inflammation and repair processes after injury via the immune system, which provides a promising therapeutic opportunity for stroke recovery.

Asunto(s)

Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Neuroinmunomodulación , Encéfalo/metabolismo

RESUMEN

BACKGROUND: A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD. METHODS: In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60 mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors. RESULTS: FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data. CONCLUSIONS: Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.

Asunto(s)

Albuminuria/patología , Tasa de Filtración Glomerular , Riñón/patología , Sistema de Registros , Insuficiencia Renal Crónica/patología , Índice de Severidad de la Enfermedad , Anciano , Albuminuria/sangre , Estudios Transversales , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/fisiopatología

RESUMEN

AIM: Multivascular disease, indicating concurrent arteriosclerotic lesions in a number of different vascular beds, is an independent risk factor for recurrent ischemic events in the general population. However, the impact of multivascular disease on the risk of developing cardiovascular disease has not been fully evaluated in patients receiving hemodialysis. METHODS: A total of 3,504 hemodialysis patients were prospectively followed for 10 years. In this study, multivascular disease was defined as the coexistence of coronary artery disease and stroke. We examined the relationship between multivascular disease and the occurrence of composite cardiovascular endpoint, consisting of cardiovascular death, nonfatal coronary artery disease, nonfatal stroke, and peripheral artery disease. RESULTS: The proportion of participants with multivascular disease was 5.7% (n=200) at baseline. During follow-up (median, 106.6 months; interquartile range, 50.1-121.8 months), 1,311 patients experienced the composite endpoint, which was defined as at least one of the following: cardiovascular death (n=620), nonfatal coronary artery disease (n=318), nonfatal stroke (n=340), and peripheral artery disease (n=257). Compared with the group with no history of cardiovascular disease, the risk of experiencing the composite endpoint increased significantly with higher numbers of injured vascular beds in patients with single vascular disease (hazard ratio, 1.68; 95% confidence interval, 1.49-1.89) and in those with multivascular disease (hazard ratio, 2.11; 95% confidence interval, 1.71-2.60). In a multivariable analysis, multivascular disease was an independent predictor of cardiovascular events, in addition to diabetes, aging, and hypertension. CONCLUSIONS: This study clearly demonstrated that multivascular disease was a powerful predictor for cardiovascular mortality and morbidity in patients receiving hemodialysis.

Asunto(s)

Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria/epidemiología , Fallo Renal Crónico , Diálisis Renal , Accidente Cerebrovascular/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Japón/epidemiología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Mortalidad , Evaluación de Resultado en la Atención de Salud , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos

RESUMEN

BACKGROUND: Several experimental studies have indicated that increased plasma osmolarity caused by recurrent dehydration is involved in kidney injury via a mechanism, mediated by vasopressin secretion and activation of the aldose reductase pathway. Epidemiologic evidence linking increased plasma osmolarity and the onset of end-stage kidney disease (ESKD), in patients with primary glomerulonephritis, is lacking. METHODS: We retrospectively examined 663 patients with IgA nephropathy (IgAN) diagnosed by kidney biopsy and evaluated the association between estimated plasma osmolarity and ESKD prevalence, using a Cox proportional hazards model. RESULTS: During follow-up (median 80.4 months; interquartile range 22.2-120.1), 73 patients developed ESKD. In a baseline survey, plasma osmolarity was correlated negatively with the mean value of the estimated glomerular filtration rate, but correlated positively with the mean value of urinary protein excretion, systolic blood pressure, and pathologic severity of extracapillary proliferation, in addition to tissue fibrosis and sclerosis. The incidence rate of ESKD increased linearly with increase in plasma osmolarity (P < 0.05 for trend). In multivariate analyses, plasma osmolarity was an independent risk factor for ESKD (hazard ratio for each increment of 5 mOsm/kg in plasma osmolarity 1.56; 95% confidence interval 1.18-2.07) even after adjustment for potential confounders. CONCLUSIONS: Increased plasma osmolarity was associated significantly with an increased risk of ESKD in patients with IgAN. Maintenance of plasma osmolarity by appropriate control of the balance between salt and water may contribute to kidney protection.

Asunto(s)

Glomerulonefritis por IGA/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Plasma/química , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/fisiopatología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Concentración Osmolar , Prevalencia , Modelos de Riesgos Proporcionales , Factores de Riesgo , Adulto Joven

RESUMEN

Inflammation plays a key role in the pathogenesis of cardiovascular diseases via the development of atherosclerosis. Here, we evaluated the impact of serum C-reactive protein (CRP) and the white blood cell (WBC) count on the risk of hypertension in middle-aged Japanese men at a work site. We evaluated a total of 2991 Japanese male workers without hypertension who ranged in age from 18 to 64 years (mean age 40.4 ± 0.2 years) at a worksite in 2010. The hazard ratio (HR) for incident hypertension was estimated according to quartile levels of serum high-sensitivity CRP (hs-CRP) or WBC count. These men were followed up for 5 years from 2010 to 2015. During the follow-up period, 579 (19.4%) subjects developed hypertension. In a multivariable analysis, the risk of incident hypertension was significantly increased with higher hs-CRP levels: HR 1.00 (reference) for the lowest quartile, 1.39 (1.04-1.85) for the 2nd quartile, 1.46 (1.08-1.98) for the 3rd quartile, and 1.57 (1.17-2.11) for the highest quartile. In contrast, the WBC count was not associated with a greater risk of incident hypertension after multivariable adjustment. These findings suggest that higher levels of serum hs-CRP, but not the WBC count, are associated with the future incidence of hypertension in middle-aged Japanese men.

Asunto(s)

Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/metabolismo , Hipertensión/epidemiología , Inflamación/sangre , Adulto , Aterosclerosis/complicaciones , Determinación de la Presión Sanguínea/métodos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Incidencia , Inflamación/complicaciones , Japón/epidemiología , Recuento de Leucocitos/estadística & datos numéricos , Masculino , Medición de Riesgo , Factores de Riesgo , Lugar de Trabajo

RESUMEN

BACKGROUND: Differential diagnosis between acute ischemic stroke (AIS) and epilepsy-related stroke mimics is sometimes difficult in the emergency department. We investigated whether a combination of diffusion-weighted imaging (DWI) and arterial spin labeling imaging (ASL) is useful in distinguishing AIS from epileptic disorders. METHODS: The study included suspected AIS patients who underwent emergency MRI including both DWI and ASL, and who exhibited DWI high-intensity lesions corresponding to neurological symptoms. We investigated the relationship between the ASL results from within and/or around DWI lesions and the final clinical diagnosis. RESULTS: Eighty-five cases were included (mean age, 71 ± 13 years; 47 men). The time from onset to the MRI examination was 493 ± 536 minutes. ASL showed hyperintensity in 13 patients, isointensity in 43, and hypointensity in 29. All ASL hyperintensities were observed in the cortex, with 4 patients (31%) presenting with AIS and 9 (69%) with an epileptic disorder. All of the AIS patients with ASL hyperintensity were diagnosed with cardioembolic stroke (4/4, 100%), with magnetic resonance angiography demonstrating recanalization of the occluded artery in all cases (4/4, 100%). In the 9 patients with an epileptic disorder, the area of ASL hyperintensity typically extended beyond the vascular territory (7/9, 78%) and involved the ipsilateral thalamus (7/9, 78%). All patients with ASL isointensity and hypointensity were diagnosed with AIS; none had epileptic disorders. CONCLUSIONS: Although cortical ASL hyperintensity can indicate cardioembolic stroke with recanalization, hyperintensity beyond the vascular territory may alternatively suggest an epileptic disorder in suspected AIS patients with DWI lesions.

Asunto(s)

Isquemia Encefálica/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Epilepsia/diagnóstico por imagen , Marcadores de Spin , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Encéfalo/fisiopatología , Isquemia Encefálica/fisiopatología , Diagnóstico Diferencial , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/fisiopatología

RESUMEN

There has been limited data discussing the relationship between apparent treatment-resistant hypertension (ATRH) and cardiovascular disease risk in patients receiving maintenance hemodialysis. We analyzed data for 2999 hypertensive patients on maintenance hemodialysis. ATRH was defined as uncontrolled blood pressure despite the use of three or more classes of antihypertensive medications, or four or more classes of antihypertensive medications regardless of blood pressure level. We examined the relationships between ATRH and cardiovascular events using a Cox proportional hazards model. The proportion of participants with ATRH was 18.0% (539/2999). During follow-up (median: 106.6 months, interquartile range: 51.3-121.8 months), 931 patients experienced cardiovascular events including coronary heart disease (n = 424), hemorrhagic stroke (n = 158), ischemic stroke (n = 344), and peripheral arterial disease (n = 242). Compared with the non-ATRH group, the ATRH group showed a significant increased risk of developing cardiovascular disease (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.08-1.49), coronary heart disease (HR: 1.28; 95% CI: 1.01-1.62), ischemic stroke (HR: 1.31; 95% CI: 1.01-1.69), and peripheral arterial disease (HR: 1.42; 95% CI: 1.06-1.91) even after adjusting for potential confounders. This study demonstrated that ATRH was significantly associated with increased cardiovascular risk in hemodialysis patients.

Asunto(s)

Hipertensión/tratamiento farmacológico , Diálisis Renal/efectos adversos , Anciano , Presión Sanguínea , Estudios de Cohortes , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Resultado del Tratamiento

RESUMEN

Professional oral health care (POHC) is known to prevent aspiration pneumonia in patients with dysphagia and/or those at the perioperative stage of surgery. However, the effect of POHC on patients suffering from aspiration pneumonia remains unknown. Here, we report a case where continual POHC intervention improved severe aspiration pneumonia. A 74-year-old male patient with a brain infarction suffered from severe aspiration pneumonia (PSI: IV, A-DROP: 3) complicated by vascular dementia and severe dysphagia. Because an antimicrobial approach following the treatment guidelines for pneumonia was not effective, we started a POHC intervention to improve his poor oral condition at the request of the attending doctor and the patient's family. The severe pneumonia markedly improved after continual POHC by the dental team. This case suggests that continual POHC intervention by a dental hygienist may improve severe aspiration pneumonia.

RESUMEN

Blood pressure variability (BPV) has been shown to be associated with cardiovascular diseases. The effects on long-term BPV of obstructive sleep apnea (OSA) are not yet known. We evaluated a total of 1653 Japanese male workers (18-69 years) at a work site to diagnose OSA, and we divided them into three groups: non-OSA (apnea-hypopnea index (AHI): < 5, n = 1414), mild-to-moderate OSA (5 ≤ AHI < 30: n = 131) and severe OSA (AHI ≥ 30: n = 108). The standard deviation and coefficient of variation of the subjects' BPV were calculated by using their annual blood pressure measurements at routine physical examinations from 2012 to 2015 (four measurements). The multivariable-adjusted BPV of systolic blood pressure (SBP) was significantly higher in the severe-OSA group compared to the non-OSA group. A multiple regression analysis also revealed that OSA was positively associated with BPV of SBP. We focused on the mild-to-moderate OSA group to evaluate the association of OSA treatment with BPV, because most of the severe-OSA subjects were being treated with continuous positive airway pressure or an oral appliance. The BPV of both systolic and diastolic blood pressure was significantly decreased in the treated subjects. These findings suggest that OSA is associated with increases in long-term BPV which was improved by the treatment of OSA in Japanese men of a work-site population.

Asunto(s)

Presión Sanguínea/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Lugar de Trabajo , Adolescente , Adulto , Anciano , Estudios Transversales , Humanos , Japón , Masculino , Persona de Mediana Edad , Polisomnografía , Factores de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/diagnóstico , Adulto Joven

RESUMEN

Inflammatory responses play a multifaceted role in regulating both disability and recovery after ischemic brain injury. In the acute phase of ischemic stroke, resident microglia elicit rapid inflammatory responses by the ischemic milieu. After disruption of the blood-brain barrier, peripheral-derived neutrophils and mononuclear phagocytes infiltrate into the ischemic brain. These infiltrating myeloid cells are activated by the endogenous alarming molecules released from dying brain cells. Inflammation after ischemic stroke thus typically consists of sterile inflammation triggered by innate immunity, which exacerbates the pathologies of ischemic stroke and worsens neurological prognosis. Infiltrating immune cells sustain the post-ischemic inflammation for several days; after this period, however, these cells take on a repairing function, phagocytosing inflammatory mediators and cellular debris. This time-specific polarization of immune cells in the ischemic brain is a potential novel therapeutic target. In this review, we summarize the current understanding of the phase-dependent role of innate myeloid cells in ischemic stroke and discuss the cellular and molecular mechanisms of their inflammatory or repairing polarization from a therapeutic perspective.

Asunto(s)

Isquemia Encefálica/inmunología , Encéfalo/inmunología , Inflamación/inmunología , Células Mieloides/inmunología , Accidente Cerebrovascular/inmunología , Animales , Encéfalo/patología , Humanos , Inmunidad Innata/fisiología , Inflamación/patología , Células Mieloides/patología , Fagocitosis/fisiología , Accidente Cerebrovascular/patología

RESUMEN

OBJECTIVE: Higher levels of serum uric acid are associated with an increased risk of cardiovascular diseases, which may be confounded by comorbidities. We investigated the effects of serum uric acid on the risk of hypertension in Japanese men at a worksite. METHODS: We evaluated a total of 2335 Japanese male workers without hypertension who ranged in age from 18 to 64 years at a worksite in 2009. These men were followed for 6 years from 2009 to 2015. RESULTS: During the follow-up period, 380 individuals developed hypertension. The odds ratio for the incident hypertension was estimated according to quartiles of serum uric acid levels of 5.1 or less, 5.2-5.8, 5.9-6.6, and at least 6.7 mg/dl. The multivariable-adjusted risk of incident hypertension was significantly higher in the highest serum uric acid quartile than in the lowest: odds ratio 1.00 (reference) for the lowest quartile, 1.34 (0.91-1.97) for the second quartile, 1.42 (0.97-2.06) for the third quartile, and 1.65 (1.14-2.40) for the highest quartile. In stratified analyses, the association between serum uric acid and incident hypertension was significant in the patients of aged below 45 years and without comorbidities, namely diabetes and low levels of high-density lipoprotein-cholesterol. CONCLUSIONS: Serum uric acid levels were associated with the future incidence of hypertension, and the association was observed in the younger individuals, those without diabetes, and those with preserved high-density lipoprotein cholesterol levels in a worksite population of Japanese men.

Asunto(s)

Hipertensión/epidemiología , Ácido Úrico/sangre , Adolescente , Adulto , Estudios de Seguimiento , Humanos , Hipertensión/sangre , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Lugar de Trabajo , Adulto Joven

RESUMEN

Background: There are limited data on secular trends in the incidence of end-stage renal disease (ESRD) and frequencies of its risk factors or treatment modalities in patients with immunoglobulin A nephropathy (IgAN). Methods: This study divided 1255 patients with IgAN into three groups according to the timing of renal biopsy: 1979-89 (n = 232), 1990-99 (n = 574) and 2000-10 (n = 449). The age-adjusted incidence rates, incidence rate ratios and 95% confidence intervals (CIs) for ESRD were calculated by the person-year method and compared using Poisson regression analysis. Results: A total of 63 patients (5.0%) developed ESRD. The age-adjusted incidence of ESRD decreased significantly over time, i.e. 11.5 per 1000 person-years (95% CI 5.4-24.6) in 1979-89, 6.5 per 1000 person-years (95% CI 1.0-25.2) in 1990-99 and 4.2 per 1000 person-years (95% CI 1.0-17.7) in 2000-10. The proportions of patients with preserved renal function and acute-stage inflammatory histologic changes (i.e. endocapillary hypercellularity and extracapillary proliferation) at the timing of biopsy increased over time, as did the rates of prescriptions of renin-angiotensin system blockers and corticosteroids (all P for trend <0.05). The effect of acute inflammatory histologic lesions on renal prognosis was drastically reduced over time. Conclusions: These findings suggest that early diagnosis in the acute inflammatory phase and subsequent aggressive treatment may have contributed to the significant downward trend in the incidence of ESRD in patients with IgAN over three decades.

Asunto(s)

Glomerulonefritis por IGA/fisiopatología , Inflamación/complicaciones , Fallo Renal Crónico/epidemiología , Adulto , Femenino , Humanos , Incidencia , Japón/epidemiología , Fallo Renal Crónico/etiología , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

The association between blood urea nitrogen to creatinine ratio (UCR) and survival is uncertain in hemodialysis patients. We examined the influence of UCR on mortality and morbidity in hemodialysis patients. A total of 3,401 hemodialysis patients were prospectively followed for 4 years. The association between UCR with overall survival was analyzed using a Cox regression model. During a 4-year follow-up period, 545 patients died from any cause and 582 experienced MACE, 392 with coronary heart disease (CHD), 114 with infection-related death, 77 with hemorrhagic stroke, 141 with ischemic stroke, and 107 with cancer death. Every 1 increase in UCR level was significantly associated with an increased risk for all-cause mortality (hazard ratio [HR] 1.07; 95% confidence interval [CI] 1.03-1.12), CHD (HR 1.08; 95% CI 1.02-1.14), and infection-related death (HR 1.11; 95% CI 1.02-1.21). There was no evidence of a significant association between UCR and death from cancer, and incidence of stroke. A high UCR was significantly associated with an increased risk for all-cause mortality, infection-related death and incidence of CHD in hemodialysis patients.

Asunto(s)

Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Diálisis Renal/mortalidad , Anciano , Causas de Muerte , Enfermedades Transmisibles/sangre , Enfermedades Transmisibles/mortalidad , Enfermedad Coronaria/sangre , Enfermedad Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/mortalidad , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Análisis de Supervivencia

Asunto(s)

Lesión Renal Aguda/etiología , Conservadores de la Densidad Ósea/efectos adversos , Calcio/sangre , Denosumab/efectos adversos , Hidroxicolecalciferoles/efectos adversos , Hipercalcemia/inducido químicamente , Hipocalcemia/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Lesión Renal Aguda/sangre , Lesión Renal Aguda/fisiopatología , Anciano de 80 o más Años , Biomarcadores/sangre , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Hipercalcemia/sangre , Hipercalcemia/fisiopatología , Hipocalcemia/sangre , Hipocalcemia/inducido químicamente , Hipocalcemia/fisiopatología , Riñón/fisiopatología , Osteoporosis/complicaciones , Osteoporosis/fisiopatología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología

RESUMEN

Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.

Asunto(s)

Alarminas/inmunología , Encéfalo/inmunología , Infarto de la Arteria Cerebral Media/inmunología , Factor de Transcripción MafB/inmunología , Células Mieloides/inmunología , Receptores Inmunológicos/inmunología , Receptores Depuradores de Clase A/inmunología , Animales , Benzoatos/farmacología , Encéfalo/efectos de los fármacos , Isquemia Encefálica/inmunología , Sistemas CRISPR-Cas , Calgranulina A/inmunología , Calgranulina B/inmunología , Inmunoprecipitación de Cromatina , Proteína HMGB1/inmunología , Inflamación , Factor de Transcripción MafB/efectos de los fármacos , Factor de Transcripción MafB/genética , Ratones , Células Mieloides/metabolismo , Peroxirredoxinas/inmunología , Receptores Inmunológicos/genética , Receptores de Ácido Retinoico/agonistas , Receptores Depuradores de Clase A/efectos de los fármacos , Receptores Depuradores de Clase A/genética , Accidente Cerebrovascular/inmunología , Tetrahidronaftalenos/farmacología

RESUMEN

As fibroblast growth factor 23 (FGF23) has been shown to induce cardiovascular disease directly in patients with chronic kidney disease, identification of factors and treatments that can modulate serum FGF23 (sFGF23) level is clinically important. This retrospective longitudinal study investigated factors that modulate sFGF23 in 49 patients who underwent peritoneal dialysis (PD). sFGF23 ratio (sFGF23 at 18 months/baseline sFGF23) was used as an indicator of changes in sFGF23 level. Total phosphate elimination was the sum of both renal phosphate excretion and dialysate phosphate elimination. In multivariate analysis, log sFGF23 ratio was associated negatively with total phosphate elimination and the use of cinacalcet at baseline, and positively with the use of vitamin D receptor activators at baseline, even after adjusting for potential confounding factors. Our study indicates that maintaining phosphate elimination can prevent increased sFGF23, thereby preventing cardiovascular events in patients who undergo PD.

Asunto(s)

Factores de Crecimiento de Fibroblastos/sangre , Diálisis Peritoneal , Fosfatos/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia , Biomarcadores/metabolismo , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Post-ischemic inflammation is re-appraised as an important player in the progression of ischemic stroke. Activation of inflammatory cells via Toll-like receptor 2 (TLR2) and TLR4 is caused by several damage-associated molecular patterns (DAMPs), including high mobility group box-1 (HMGB-1) and heat shock proteins. We have recently found that peroxiredoxin (Prx) is one of the strong DAMPs and activates infiltrating macrophages in brain ischemia. We have also found that interleukin-23 (IL-23) from the activated macrophages stimulates γδT cells which release IL-17, thereby causing the delayed expansion of infarct lesions. Further investigation of the innate immune response would lead to development of novel stroke treatment with a broad therapeutic time window.

Asunto(s)

Inflamación/genética , Accidente Cerebrovascular , Encéfalo/patología , Progresión de la Enfermedad , Proteína HMGB1 , Proteínas de Choque Térmico , Humanos , Inmunidad Innata , Inflamación/inmunología , Interleucina-17 , Interleucina-23 , Activación de Macrófagos , Peroxirredoxinas/fisiología , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/inmunología , Receptor Toll-Like 2 , Receptor Toll-Like 4