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INTRODUCTION: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. RESULTS: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.
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Fallo Renal Crónico , Diálisis Renal , Calcificación Vascular , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Anciano , Estudios de Cohortes , Densidad ÓseaRESUMEN
BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Glomérulos Renales , Humanos , Nefropatías Diabéticas/patología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Glomérulos Renales/patología , Anciano , Tasa de Filtración Glomerular , Estudios de Cohortes , Biopsia , Fallo Renal Crónico , Factores de RiesgoRESUMEN
Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome data sets, 38 DEPs were organized; only ten DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin, were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multisample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.
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Espectrometría de Masas/métodos , Proteómica/métodos , Insuficiencia Renal Crónica/metabolismo , Adulto , Anciano , Animales , Apoptosis , Biomarcadores/metabolismo , Biomarcadores/orina , Células Cultivadas , Células Epiteliales/metabolismo , Femenino , Fibrosis , Humanos , Riñón/citología , Riñón/metabolismo , Riñón/patología , Masculino , Persona de Mediana Edad , Proteoma/metabolismo , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/orina , Adulto JovenRESUMEN
Obesity is a major health problem worldwide and is associated with chronic kidney disease (CKD). Body mass index (BMI) is a common method of diagnosing obesity, but there are concerns about its accuracy and ability to measure body composition. This study evaluated the risk of CKD development in a middle-aged population in association with various body composition metrics. From a prospective cohort of 10,030 middle-aged adults, we enrolled 6727 for whom baseline and follow-up data were available. We collected data pertaining to participants' BMI, manually measured waist-hip ratio (WHR), and various measurements of bioelectrical impedance analysis (BIA), including total body fat content, muscle content, and calculated WHR, and classified the participants into quintiles accordingly. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 in follow-up laboratory tests. While an increase in BMI, WHR, and total body fat were associated with an elevated risk of CKD, an increase in total body muscle decreased the risk. Among the body composition metrics, WHR measured by BIA had the highest predictive value for CKD (C-statistics: 0.615). In addition, participants who were "healthy overweight, (defined as low WHR but high BMI), exhibited a 62% lower risk of developing CKD compared to those with "normal-weight obesity," (defined as high WHR despite a normal BMI). In conclusion, we suggest that central obesity measured by BIA is a more accurate indicator than BMI for predicting the development of CKD.
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Insuficiencia Renal Crónica , Persona de Mediana Edad , Adulto , Humanos , Relación Cintura-Cadera , Impedancia Eléctrica , Estudios Prospectivos , Índice de Masa Corporal , Insuficiencia Renal Crónica/complicaciones , Obesidad/epidemiologíaRESUMEN
BACKGROUND: Benzo(a)pyrene (BaP) is a carcinogenic compound in contaminated foodstuffs. The effect of oral intake of the environmental carcinogen BaP under low doses and frequent exposure on a digestive system has not been thoroughly verified. METHODS: In this regard, this study was conducted to prove the toxicity effects of BaP on the stomach and colon tissue after exposure to C57BL/6 mouse (3 and 6 µg/kg) following daily oral administration for 60 days. This study investigated acute gastric mucosal injury, severe gastric edema, cell infiltration, and mononuclear cells, multifocal cells, and tumoral inflammatory cells. RESULTS: The results of ELISA showed that the expression of serum interleukin (IL)-6 and tumor necrosis factor-α in the BaP exposure group were significantly increased, and a high level of DNA adduct distribution in their stomach and colon. Moreover, this study has confirmed the expression of early carcinogenesis markers: nuclear factor (NF)-κB, p53, IL-6, superoxide dismutase 1 (SOD1), mucin (MUC1 and MUC2), and ß-catenin in the stomach and colon, and showed that there was a significant increase in IL-6, NF-κB, SOD1, ß-catenin, and MUC1 (P < 0.05). At the same time, there was a significant decrease in MUC2 and p53 (P < 0.05). Thus, even in low doses, oral intake of BaP can induce DNA damage, increasing the potential risk of gastrointestinal cancer. CONCLUSION: This study will provide a scientific basis for researching environmental contaminated food and intestinal health following daily oral administration of BaP.
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Neoplasias Gastrointestinales , beta Catenina , Animales , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidad , Neoplasias Gastrointestinales/inducido químicamente , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , Superóxido Dismutasa-1/metabolismo , Proteína p53 Supresora de Tumor , beta Catenina/metabolismoRESUMEN
Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.
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Adipoquinas/metabolismo , Síndrome Metabólico/patología , Animales , Humanos , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismoRESUMEN
BACKGROUND: The renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on individual differences in body fluid distribution and risk of chronic dehydration. METHODS: We conducted a cross-sectional analysis of the 2008-2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (< 20 mL/kg/day), low-moderate (20-29.9 mL/kg/day), high-moderate (30-49.9 mL/kg/day), and highest (≥ 50 mL/kg/day). We assessed the risk of renal impairment (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2) according to water intake. RESULTS: In total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day. CONCLUSIONS: High daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.
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Deshidratación/prevención & control , Ingestión de Líquidos , Tasa de Filtración Glomerular , Enfermedades Renales/prevención & control , Riñón/fisiopatología , Equilibrio Hidroelectrolítico , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Bases de Datos Factuales , Deshidratación/epidemiología , Deshidratación/fisiopatología , Femenino , Humanos , Enfermedades Renales/epidemiología , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Estado de Hidratación del Organismo , Prevalencia , Factores Protectores , Ingesta Diaria Recomendada , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Acute pyelonephritis (APN) is a common infection during pregnancy that increases the risk of unfavorable maternal and fetal outcomes. However, it has not been clearly elucidated which demographic and clinical characteristics are associated with the incidence of APN during pregnancy. OBJECTIVE: This population-based cohort study aimed to determine the risk factors for APN during pregnancy. METHODS: Using the database of the Health Insurance Review and Assessment Service of South Korea, we enrolled Korean women who delivered infants between 2010 and 2014 in Korea and had complete health examination records within 1 year of pregnancy. We performed multivariate logistic regression analysis to evaluate the risk factors for APN during pregnancy. RESULTS: Of 370,248 women, 2,526 (0.7% of the total participants) were treated for APN while in hospitalization during pregnancy. Younger age, history of previous APN within 1 year of pregnancy, and abnormal results of health examination before pregnancy, such as high fasting glucose level (>100 mg/dL) and proteinuria, were associated with an increased risk of APN during pregnancy. CONCLUSION: Certain maternal demographic and clinical characteristics were associated with the incidence of APN during pregnancy, and these should be monitored closely during antenatal care.
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Pielonefritis/diagnóstico , Enfermedad Aguda , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Embarazo , Pielonefritis/patología , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.
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Necrosis Tubular Aguda/diagnóstico , Riñón/patología , Nefritis Intersticial/diagnóstico , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/etiología , Necrosis Tubular Aguda/complicaciones , Necrosis Tubular Aguda/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/complicaciones , Nefritis Intersticial/patología , Proteinuria/etiología , Factores de RiesgoRESUMEN
AIM: Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients. METHODS: A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months. RESULTS: Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953). CONCLUSION: Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.
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Espectroscopía Dieléctrica/métodos , Fluidoterapia/métodos , Fallo Renal Crónico , Diálisis Peritoneal , Desequilibrio Hidroelectrolítico , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Estado de Hidratación del Organismo , Evaluación de Resultado en la Atención de Salud , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/fisiopatología , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
BACKGROUND/AIMS: SIRT1 activation promotes the resistance of renal tubular cells to oxidative stress, and resveratrol is known as a SIRT1 activator. METHODS: Resveratrol was injected intraperitoneally with iohexol for 24 hours. NRK-52E cells were pretreated with resveratrol for 24 hours and then exposed to iohexol for 3 hours. Renal function was measured by serum creatinine and cell survival was assessed by MTT assay. We investigated whether resveratrol attenuates oxidative stress and apoptosis in contrast-induced nephropathy (CIN). RESULTS: Serum creatinine and tubular injury increased significantly after iohexol treatment, and resveratrol co-treatment attenuated the renal injury. Cell survival decreased after iohexol exposure and resveratrol reduced cell death induced by iohexol. Resveratrol was accompanied with the activation of SIRT1 and PGC-1α and dephosphorylation of FoxO1 in mice with CIN. SIRT1 and PGC-1α expression were decreased by iohexol, and increased significantly in resveratrol-pretreated cells. These processes resulted in reduction of oxidative stress and apoptosis both in vivo and in vitro experiments. Resveratrol decreased inflammatory cell infiltration induced by iohexol in mice with CIN. SIRT1 inhibition using siRNA in tubular cells accentuated the decrease of cell viability by iohexol. CONCLUSION: Resveratrol attenuated CIN by modulating renal oxidative stress and apoptosis through activation of SIRT1-PGC-1α-FoxO1 signaling.
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Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Transducción de Señal , Sirtuina 1/metabolismo , Estilbenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteína Forkhead Box O1/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Resveratrol , Estilbenos/uso terapéuticoRESUMEN
UNLABELLED: Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients. METHODS: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months; <-1, -1 - -0.1, -0.1 - +1, and ≥+1L). The relations of OH difference with HRQOL scores at 12 months and the association of OH difference with the HRQOL score difference (HRQOL score at baseline - HRQOL score at 12 months) were assessed. RESULTS: The OH group showed significantly lower baseline physical and mental health scores (PCS and MCS), and kidney disease component scores (KDCS) compared with the NH group (all, P<0.01). At 12 months, the adjusted PCS, MCS, and KDCS significantly increased as the OH difference quartiles increased (P<0.001, P=0.002, P<0.001, respectively). In multivariate analysis, the OH difference was independently associated with higher PCS (ß = 2.04, P< .001), MCS (ß=1.02, P=0.002), and KDCS (ß=1.06, P<0.001) at 12 months. The OH difference was independently associated with the PCS difference (ß = -1.81, P<0.001), MCS difference (ß=-0.92, P=0.01), and KDCS difference (ß=-0.90, P=0.001). CONCLUSION: The hydration status was associated with HRQOL and increased hydration status negatively affected HRQOL after 12 months in PD patients.
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Deshidratación/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Enfermedades Renales/terapia , Diálisis Peritoneal/efectos adversos , Adulto , Anciano , Deshidratación/complicaciones , Espectroscopía Dieléctrica , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Calidad de Vida , Rigidez Vascular/fisiologíaRESUMEN
A 65-year-old man on continuous ambulatory peritoneal dialysis was admitted with peritonitis. Empirical antibiotic therapy was initiated, and Raoultella planticola was identified in the peritoneal fluid culture. We treated the patient with intraperitoneally administered ciprofloxacin and ceftazidime according to the antibiotic susceptibility. His condition improved, and he was well treated with a 2-week antibiotic course.
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Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/patología , Enterobacteriaceae/aislamiento & purificación , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/diagnóstico , Peritonitis/patología , Anciano , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Ciprofloxacina/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Humanos , Masculino , Peritonitis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Cinacalcet is one of the important treatments of secondary hyperparathyroidism (SHPT). We evaluated the role of computed tomography (CT) for parathyroid glands (PTGs) to determine the response to cinacalcet therapy in dialysis patients. METHODS: In study 1, we compared the predictive cutoff values of the largest volume or diameter of PTGs on ultrasonography or CT for achievement of target intact parathyroid hormone (iPTH) level according to K/DOQI guideline after cinacalcet treatment in a single dialysis center. In study 2, the role of the cutoff diameter of PTGs on CT in predicting responsive to cinacalcet therapy was reevaluated in dialysis patients with SHPT in multiple centers. RESULTS: In study 1, among the total population of 26 patients, the number of patients with baseline iPTH over 600 pg/mL was 16 (61%). In study 2, it was 45 (54%), among 82 patients. In study 1, the number of PTGs equal to or larger than the cutoff value (≥ 11.2 mm) on CT, not ultrasonography, was significantly higher in non-responders than in responders (p=0.038). In study 2, the proportion of patients with PTGs ≥ 11.2 mm on CT was significantly higher in non-responders than responders (p=0.003). Multivariate analysis showed that pretreatment iPTH (odds ratio [OR] 1.498, p=0.003) and the existence of enlarged PTGs on CT (OR 8.940, p=0.015) were significant clinical factors affecting the response to cinacalcet. CONCLUSIONS: The diameter of PTGs on CT could predict the response to cinacalcet in dialysis patients with SHPT.
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Calcimiméticos/uso terapéutico , Cinacalcet/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Glándulas Paratiroides/diagnóstico por imagen , Diálisis Renal , Adulto , Anciano , Femenino , Humanos , Hiperparatiroidismo Secundario/complicaciones , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Valor Predictivo de las Pruebas , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , UltrasonografíaRESUMEN
AIM: The intrarenal renin-angiotensin system (RAS) has been reported to be activated in chronic proteinuria patients. This study aimed to compare intrarenal RAS activity between diabetic nephropathy (DN) and non-diabetic nephropathy (NDN) patients with overt proteinuria. METHODS: A multicenter, cross-sectional study was conducted in 116 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] > 1 mg/mg Cr). To estimate intrarenal RAS activity we measured urinary excretion of angiotensinogen (uAGT) and renin (uRenin) in patients with DN (n = 38) and NDN (n = 78). RESULTS: Both natural logarithms of uAGT/urinary creatinine (ln[uAGT/uCr]) and uRenin (ln[uRenin/uCr]) levels were significantly higher in patients with DN compared with those with NDN (ln[uAGT/uCr]: 4.16 ± 1.13 in DN vs. 3.52 ± 1.21 in NDN, P = 0.007; ln[uRenin/uCr]: 5.66 ± 1.60 in DN vs. 4.29 ± 1.48 in NDN, P < 0.001), when estimated glomerular filtration rate (eGFR) and uPCR showed no significant difference between the two groups. In a subgroup analysis, according to amount of proteinuria, both uAGT and uRenin were higher in DN in patients with subnephrotic-range proteinuria (uPCR < 3.5 mg/mg Cr). However, in patients with nephrotic-range proteinuria (uPCR ≥ 3.5 mg/mg Cr), only uRenin was higher in DN compared to NDN. In a multiple regression analysis, diabetes showed independent association with uRenin. CONCLUSION: Consistently elevated uRenin in DN, regardless of the amount of proteinuria, indicates that intrarenal RAS activity may be higher in DN compared to NDN in patients with overt proteinuria.
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Nefropatías Diabéticas/orina , Riñón/metabolismo , Proteinuria/orina , Sistema Renina-Angiotensina , Renina/orina , Adulto , Anciano , Angiotensinógeno/orina , Biomarcadores/orina , Creatinina/orina , Estudios Transversales , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteinuria/diagnóstico , Proteinuria/etiología , República de Corea , Estudios Retrospectivos , Regulación hacia ArribaRESUMEN
We conducted a study to determine whether the hemocontrol biofeedback system (HBS) can improve intradialytic hypotension (IDH) in hypotension-prone hemodialysis (HD) patients compared with conventional HD. In this multicenter prospective crossover study, 60 hypotension-prone patients were serially treated by conventional HD for 8 weeks (period A), by HD with hemoscan blood volume monitoring for 2 weeks (period B0), and by HBS HD for 8 weeks (period B1). The number of sessions complicated by symptomatic IDH during 24 HD sessions (14.9 ± 5.8 sessions, 62.1% in period A vs 9.2 ± 7.2 sessions, 38.4% in period B1, P<0.001) and the number of IDH-related nursing interventions in a session (0.96 ± 0.66 in period A vs 0.56 ± 0.54 in period B1, P<0.001) significantly decreased in period B1 than in period A. Recovery time from fatigue after dialysis was significantly shorter in period B1 than in period A. The patients with higher post-dialysis blood pressure, lower difference between pre- and post-dialysis blood pressure, less frequent IDH, and higher pre- and post-dialysis body weight in period A responded better to HBS in period B1 in regard to the reduction of IDH. In conclusion, HBS may improve the patient tolerability to HD by reducing the IDH frequency and promoting faster recovery from fatigue after dialysis.
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Biorretroalimentación Psicológica , Hipotensión/prevención & control , Fallo Renal Crónico/terapia , Adolescente , Adulto , Anciano , Presión Sanguínea , Volumen Sanguíneo , Peso Corporal , Estudios Cruzados , Fatiga , Femenino , Humanos , Hipotensión/etiología , Masculino , Persona de Mediana Edad , Posición Prona , Estudios Prospectivos , Diálisis Renal/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase (α-Gal A), affecting multiple organs including kidney. In this study, we aimed to determine the prevalence of FD in patients with chronic kidney disease (CKD) including those on renal replacement therapy in Korea. METHODS: This is a national, multicenter, observational study performed between August 24, 2017 and February 28, 2020. Patients with the presence of proteinuria or treated on dialysis were screened by measuring the α-Gal A enzyme activity using either dried blood spot or whole blood, and plasma globotriaosylsphingosine (lyso-GL3) concentration. A GLA gene analysis was performed in patients with low α-Gal A enzyme activity or increased plasma lyso-GL3 concentration. RESULTS: Of 897 screened patients, 405 (45.2%) were male and 279 (31.1%) were on dialysis. The α-Gal A enzyme activity was measured in 891 patients (99.3%), and plasma lyso-GL3 concentration was measured in all patients. Ten patients were eligible for a GLA gene analysis: eight with low α-Gal A enzyme activity and two with increased plasma lyso-GL3 concentration. The GLA mutations were analyzed in nine patients and one patient was found with a pathogenic mutation. Therefore, one patient was identified with FD, giving a prevalence of 0.1% (1 of 897) in this CKD population. CONCLUSION: Although the prevalence of FD in the CKD population was low (0.1%), screening tests are crucial to detect potential diseases in patients with relatives who can benefit from early treatment.
RESUMEN
Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.
Asunto(s)
Apoptosis , Ciclosporina , Ratones Noqueados , Mitocondrias , Estrés Oxidativo , Sirtuina 3 , Animales , Sirtuina 3/metabolismo , Sirtuina 3/genética , Ciclosporina/efectos adversos , Ciclosporina/toxicidad , Ciclosporina/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones , Perros , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Células de Riñón Canino Madin Darby , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/prevención & control , Enfermedades Renales/patología , Enfermedades Renales/genética , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Ratones Endogámicos C57BL , Masculino , Transducción de Señal/efectos de los fármacosRESUMEN
Despite medical progress, high morbidity and mortality rates have persisted in patients with end-stage renal disease (ESRD). The role in atherosclerosis and cardiovascular disease of klotho, an aging process-related gene, has been highlighted. Genetic variation in klotho has been reported to be a risk factor for coronary artery disease and ischemic stroke. Regarding the significance of cardiovascular disease for the outcome of ESRD patients, we investigated whether genetic variation of klotho was associated with mortality in ESRD patients on hemodialysis. 478 patients on maintenance hemodialysis for more than 3 months at dialysis facilities affiliated with the Western Dialysis Physician Association were enrolled in September 2004. Patient survival was checked annually until September 2007. Genotypings of klotho in terms of G395A in the promoter region, C1818T in exon 4, and KL-VS was performed. 45 deaths (11.2%) occurred over 3 years. Mortality was higher in the GA+AA group than in the GG group (18.9% vs. 6.7%, respectively, p < 0.001). Kaplan-Meier analysis also revealed that the survival of the GA+AA group was worse than that of GG group (p = 0.002). Cox's proportional hazards regression analysis showed that age, A allele carrier status in G395A of klotho, hemoglobin, albumin and HDL cholesterol levels were the significant factors affecting survival of hemodialysis patients. The A allele of the G395A polymorphism of klotho may be associated with the risk of mortality in Korean hemodialysis patients. Age, hemoglobin, albumin and HDLC were also significant prognostic factors for survival in the present study.
Asunto(s)
Enfermedades Cardiovasculares/genética , ADN/genética , Glucuronidasa/genética , Fallo Renal Crónico/complicaciones , Polimorfismo Genético , Diálisis Renal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Genotipo , Glucuronidasa/metabolismo , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Proteínas Klotho , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
The authors present a rare of prenatally diagnosed congenital anaplastic astrocytoma. A 9-month-old boy had three recurrences despite two surgical resections and various chemotherapeutic regimens. He underwent the 3rd gross tumor removal at 11 months of age, followed by proton therapy, and now he remains disease-free for 3 yr without a significant neurocognitive dysfunction. This is the 1st case of a pediatric tumor treated by proton therapy in Korea, and proton therapy may be a treatment of choice for a congenital anaplastic astrocytoma in infants and young children, considering limitation of radiation therapy.