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Background: Patients with end-stage kidney disease (ESKD) are more susceptible to viral epidemics and are known to have higher incidence and death rates of coronavirus disease 2019 (COVID-19) compared to the general population. We determined COVID-19 incidence and mortality among chronic hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT) patients in Korea. Methods: We conducted a retrospective cohort study and data regarding Korean ESKD adults (aged ≥18 years) were obtained from the National Health Insurance Service of Korea from October 2020 to December 2021. We examined and compared the incidence of COVID-19-related infections and deaths among the patients receiving HD, PD, and KT. Results: Of all ESKD patients, 85,018 (68.1%) were on HD, 8,399 (6.7%) on PD, and 31,343 (25.1%) on KT. The COVID-19 incidence was 1.3% for HD, 1.2% for PD, and 1.5% for KT. COVID-19 mortality was 16.3% for HD, 12.2% for PD, and 4.7% for KT. PD patients had a lower incidence of infection compared to HD patients (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.607-0.93), but KT patients had a significantly higher risk of infection (OR, 1.28; 95% CI, 1.13-1.44). Compared with HD, the risk of COVID-19-related death was not different for PD patients but was significantly lower for KT patients (hazard ratio, 0.55; 95% CI, 0.35-0.88). Conclusion: COVID-19 incidence was lower in PD patients than in HD patients, but mortality was not different between them. KT was associated with a higher risk of COVID-19 infection but lower mortality compared to HD.
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Background: Patients undergoing hemodialysis (HD) have a high risk of novel coronavirus disease 2019 (COVID-19) and poor clinical outcomes. This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against infection and deaths in the South Korean population undergoing HD. Methods: We conducted a retrospective cohort study to compare the incidence of COVID-19 and post-diagnosis mortality between patients who were either never vaccinated or fully or partially vaccinated. The Korean nationwide COVID-19 registry and the Korean National Health Insurance Service databases were used. Adult patients without a history of COVID-19 were included between October 8, 2020, and December 31, 2021. The study outcomes were COVID-19 diagnosis, severe clinical COVID-19-related events, and post-diagnosis death. Results: Eighty-five thousand eighteen patients undergoing HD were included, of whom 69,601 were fully vaccinated, 2,213 were partially vaccinated and 13,204 were unvaccinated. Compared with the unvaccinated group, the risk of being diagnosed with COVID-19 in patients who were fully vaccinated decreased during the study period (adjusted odds ratio [aOR] = 0.147; 95% confidence interval [CI] = 0.135-0.159). There were 1,140 (1.3%) patients diagnosed with COVID-19. After diagnosis, fully vaccinated patients were significantly less likely to die than unvaccinated patients (aOR = 0.940; 95% CI = 0.901-0.980) and to experience severe clinical events (aOR = 0.952; 95% CI = 0.916-0.988). Conclusion: Full vaccination against COVID-19 was associated with a reduced risk of both infection and severe clinical outcomes in the South Korean population undergoing HD. These findings support the use of vaccination against SARS-CoV-2 among patients undergoing HD.
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Vacunas contra la COVID-19 , COVID-19 , Diálisis Renal , SARS-CoV-2 , Humanos , República de Corea/epidemiología , COVID-19/prevención & control , COVID-19/mortalidad , COVID-19/epidemiología , Masculino , Femenino , Diálisis Renal/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Eficacia de las Vacunas/estadística & datos numéricos , Adulto , Vacunación/estadística & datos numéricos , Estudios de Cohortes , IncidenciaRESUMEN
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
OBJECTIVE: The Geriatric Nutritional Risk Index is a simple nutritional screening method, and this study aimed to investigate the association between the initial Geriatric Nutritional Risk Index and all-cause mortality in incident patients in the first year after the initiation of hemodialysis. MATERIALS AND METHODS: This study is a retrospective cohort study and used the Korean Renal Data System database. Patients who were eligible for Geriatric Nutritional Risk Index assessment and underwent hemodialysis from January 2016 to December 2019 were included. The primary outcome was all-cause mortality, and outcome evaluation was performed in December 2020. A Cox proportional hazard model was used to analyze the association between the Geriatric Nutritional Risk Index and mortality. RESULTS: A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. The patients were divided into four groups by the quartile of the Geriatric Nutritional Risk Index with a mean value of 96.2 ± 8.2. During the study period, 545 (5.2%) deaths occurred. The surviving patients had higher Geriatric Nutritional Risk Index values than ones who died in the first year of hemodialysis initiation (96.6 ± 7.5 vs. 88.2 ± 9.3, p < 0.001). Quartile 1 (Geriatric Nutritional Risk Index < 91.8) showed a significantly increased risk of all-cause (Hazard Ratio: 2.56; 95% Confidence Interval: 2.13-3.09; p < 0.001) and cardiovascular mortality (Hazard Ratio: 22.29; 95% Confidence Interval: 1.71- 3.08; p < 0.001) at the first year in comparison with Quartile 4 (Geriatric Nutritional Risk Index ≥ 101.3). In areas under the receiver-operating characteristic curves of all-cause mortality, the Geriatric Nutritional Risk Index model improved predictive values, compared to the baseline model. The area with the Geriatric Nutritional Risk Index model was significantly higher than the one with a model including albumin or body mass index (p < 0.001). CONCLUSIONS: These findings suggest that a low Geriatric Nutritional Risk Index (<91.8) is associated with first-year all-cause and cardiovascular mortality in patients who start hemodialysis and may be a useful and reproducible tool for assessing prognoses in this population.
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Enfermedades Cardiovasculares , Evaluación Nutricional , Humanos , Anciano , Persona de Mediana Edad , Estado Nutricional , Estudios Retrospectivos , Diálisis Renal , Evaluación Geriátrica/métodos , Factores de Riesgo , Medición de RiesgoRESUMEN
Background: Hemodialysis (HD) patients have a higher mortality rate compared to the general population. However, no study has investigated life expectancy in Korean HD patients so far. Therefore, this study aimed to calculate the remaining life expectancy among Korean maintenance HD patients and compare it to those of the general population as well as HD patients from other countries. Methods: Baseline data were retrieved from HD quality assessment data from 2015. Among the patients over 30 years old who were alive at the beginning of 2016 (20,304 males and 14,264 females), a total of 22,078 (12,621 males and 9,457 females) were still alive at the end of 2021 while 12,490 (7,683 males and 4,807 females) were deceased during 6 years of follow-up. We used the life table method to calculate the expected remaining years of life in 2-year increments. Results: The remaining life expectancies for 60-year-old patients were 11.64 years for males and 14.64 years for females. The average remaining lifetimes of the HD population were only about half of the general population. Diabetic patients demonstrated shorter life expectancy compared to patients with hypertension or glomerulonephritis. The remaining life expectancy of Korean HD patients was similar to that of Japanese and was almost double that of HD patients in Western countries such as Europe and the United States. Conclusion: The HD population shows shorter life expectancy compared to the general population. Longitudinal analysis should be warranted to analyze the effect of advanced dialysis technology on improved survival rates among the HD population.
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BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19-infected patients on hemodialysis (HD). METHODS: We conducted an observational retrospective study in 230 COVID-19-infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. RESULTS: Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. CONCLUSION: Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD.
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The aim of this study was to evaluate whether the geriatric nutritional risk index (GNRI) is associated with chronic kidney disease (CKD) progression in patients with type 2 diabetes mellitus (DM). In total, 1100 patients with type 2 DM with a follow-up duration > 1 year were included in this longitudinal study. The risk of CKD progression was assessed according to GNRI quartiles. Patients in the lowest GNRI quartile exhibited a significantly lower estimated glomerular filtration rate (eGFR), compared with those in quartile four. Moreover, these patients had poorer glycemic control and lower hemoglobin levels, body mass index, and albumin levels. Additionally, they exhibited a greater annual decline in eGFR. Multivariate logistic regression analysis showed that old age (>60 years), baseline eGFR, the presence of proteinuria, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and low GNRI were significantly associated with CKD progression. GNRI may serve as a valuable predictive tool for identifying the risk of adverse renal outcomes in patients with type 2 DM. It may potentially serve as a more feasible measure for assessing the nutritional status of these patients, as well as for predicting their clinical outcomes.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Anciano , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Pronóstico , Estudios Longitudinales , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Estado Nutricional , Factores de Riesgo , Tasa de Filtración Glomerular , Progresión de la EnfermedadRESUMEN
Inflammation plays a major role in the pathogenesis of chronic kidney disease (CKD), but the relationship between systemic inflammation and CKD-mineral bone disease is unclear. We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) is related to abdominal aortic calcification (AAC) and bone mineral density (BMD) in dialysis patients. In this cross-sectional analysis using baseline data of a multicenter cohort, a total of 759 patients were divided into three groups according to NLR level, and the associations between NLR and Kauppila AAC score (AACS) and BMD were assessed. The highest tertile NLR group had more males, alcohol consumers, higher diabetes prevalence, and higher comorbidity index than the lowest tertile NLR group. Fasting glucose and C-reactive protein levels were higher, while serum albumin, serum iron, and lipid profiles except triglycerides were lower in the highest tertile group. AACS was significantly higher in the highest tertile group than in the lowest and middle tertile groups (p = 0.017), but the mean areal BMD and T-score of the lumbar spine and femur were not different between groups. NLR level was positively correlated with AACS in all aortic wall segments except L1 and L3 anterior. In multivariable logistic regression analysis, the highest tertile NLR group was independently associated with AAC (odds ratio 2.876, 95% confidence interval 1.250-6.619, p = 0.013) but was not associated with osteoporosis in the lumbar spine and femur after adjusting for confounding factors. The NLR can be used as a potential indicator of AAC in dialysis patients.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Masculino , Densidad Ósea , Relevancia Clínica , Estudios Transversales , Inflamación/complicaciones , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Linfocitos , Neutrófilos , Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/complicaciones , FemeninoRESUMEN
Routine laboratory tests are regularly performed in patients undergoing maintenance hemodialysis (HD) to detect anemia, chronic kidney disease-mineral bone disorders, and cardiovascular disease. More frequent laboratory tests may be associated with better outcomes. However, there is little evidence supporting a specific monitoring interval. This study evaluated the impact of regular laboratory testing on mortality in Korean patients undergoing maintenance HD. We used HD quality assessments, and National Health Insurance Service claims data from October to December 2015. In HD quality assessment, 22 tests are recommended every 1-6 months. A total of 34,950 patients were divided into two groups based on the regularity of laboratory testing. A Cox proportional hazards model was used to assess the effects of regular laboratory tests on patient mortality during a mean follow-up duration of 53.7 months. The proportion of patients with and without regular laboratory testing was 85.6% (n = 29,914) and 14.4% (n = 5036), respectively. Patients who underwent regular laboratory testing had a longer dialysis duration, lower serum phosphorus levels and diastolic blood pressure, and higher hemoglobin and single-pool Kt/V levels than those who did not. After adjusting for demographic and clinical parameters, regular laboratory testing independently reduced mortality risk (hazard ratio, 0.90; 95% confidence interval 0.85-0.95; P < 0.001). Regular laboratory testing was associated with a decreased mortality risk among patients undergoing HD. Management of end-stage kidney disease-related complications based on laboratory tests can improve survival.
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Enfermedades Cardiovasculares , Fallo Renal Crónico , Humanos , Diálisis Renal/efectos adversos , Estudios de Cohortes , Fallo Renal Crónico/complicaciones , Enfermedades Cardiovasculares/etiología , Modelos de Riesgos Proporcionales , República de Corea/epidemiologíaRESUMEN
The Geriatric Nutritional Risk Index (GNRI) is a nutritional screening tool used for predicting mortality in patients undergoing hemodialysis (HD). This study investigated the cutoff values for the GNRI for predicting mortality in HD patients using Korean HD quality assessment data from 2015. To identify the optimal GNRI cutoff value, we used Harrell's C-index with multivariate Cox regression models. The highest value of C-index was identified as the cutoff value of GNRI for all-cause mortality in this population. In total, 34,933 patients were included; 90.8 of GNRI was the highest value of C-index, and it was used as a cutoff value to predict mortality; 3311 patients (9.5%) had GNRI values < 90.8, and there were 12,499 deaths during the study period. The mean follow-up period was 53.7 months. The crude mortality rates in patients with GNRI values < 90.8 and ≥ 90.8 were 160.4/1000 and 73.2/1000 person-years respectively. In the fully adjusted Cox model, patients with a GNRI < 90.8 had a 1.78 times higher risk of mortality than those with a GNRI ≥ 90.8. These findings suggest that the optimal GNRI cutoff value is 90.8 for predicting mortality in maintenance HD patients.
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Evaluación Nutricional , Estado Nutricional , Adulto , Humanos , Pueblo Asiatico , Diálisis Renal , República de Corea/epidemiologíaRESUMEN
Background: In patients undergoing incident hemodialysis, increased fibroblast growth factor-23 (FGF-23) levels are associated with the development of cardiovascular disease (CVD), but the influence of residual kidney function (RFK) on this association is unclear. This study aimed to investigate the association between FGF-23 levels, RKF, and CVD in patients undergoing prevalent hemodialysis. Methods: This cross-sectional and longitudinal observational study included 296 patients undergoing maintenance hemodialysis for at least three months who were followed up for a median of 44 months. RKF was defined as 24-h urine output >200 mL, left ventricular (LV) diastolic dysfunction as E/E' >15 on echocardiographic parameters. CVD was defined as hospitalization or emergency room visits due to cardiovascular causes, such as angina, myocardial infarction, or congestive heart failure. Results: The median intact FGF-23 (iFGF-23) level was 423.8 pg/mL (interquartile range, 171-1,443). Patients with an FGF-23 level > 423.8 pg/mL significantly had a lower proportion of RKF (39.2% vs. 60.1%, P < 0.001) and a higher proportion of LV diastolic dysfunction (54. 1% vs. 29.1%, P < 0.001) than those with an iFGF-23 level ≤ 423.8 pg/mL. The odds ratio (OR) for LV diastolic dysfunction was significantly higher in patients with RFK (OR per one-unit increase in the natural log-transformed iFGF-23 levels, 1.80; 95% confidence interval [CI]: 1.11-2.93) than in patients without RKF (OR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.42; 95% CI: 1.01-1.99) in multivariate analysis (p < 0.001). During the follow-up period, 55 patients experienced CVD. The hazard ratio (HR) for CVD development was also significantly higher in patients with RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels, 2.64; 95% CI: 1.29-5.40) than those without RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.44; 95% CI: 1.04-1.99) in multivariate analysis (p = 0.05). Conclusions: Increased iFGF-23 levels were associated with LV diastolic dysfunction and CVD development in patients undergoing prevalent hemodialysis; however, the loss of RKF attenuated the magnitude of these associations. Therefore, in these patients, RKF strongly influenced the detrimental role of iFGF-23 in the development of CVD.
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Enfermedades Cardiovasculares , Fallo Renal Crónico , Disfunción Ventricular Izquierda , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factor-23 de Crecimiento de Fibroblastos , Estudios Transversales , Diálisis Renal/efectos adversos , Riñón , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiologíaRESUMEN
BACKGROUND: Patients with kidney failure must make complicated decisions about the dialysis modalities used either at home or in-hospital. Different options have varying levels of impact on patients' physical and psychological conditions and their social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision making (SDM) in patients' options for dialysis. METHODS: SDM was performed after consent was written for stage 5 chronic kidney disease patients before dialysis, and 435 cases were performed in 408 patients from December 16, 2019 to June 30, 2021. Among these, 101 patients were compared by SDM measurement scale, patient satisfaction, disease recognition scale survey, and dialysis method. RESULTS: The average age of participants was 56â years, with a gender composition of 55 males (54.5%) and 46 females (45.5%). Following SDM, the final dialysis methods decided upon by patients and clinicians were peritoneal dialysis (67 patients, 66.3%), hemodialysis (22 patients, 21.8%), and kidney transplantation (1 patient, 1.0%). CONCLUSIONS: Among participating patients, SDM was effective when used to decide on dialysis treatment, and patients were satisfied with the dialysis method decision process. On the disease awareness scale, those who participated in this project had relatively high positive and low negative perceptions, so it can be concluded that SDM was relatively effective. The implementation of SDM was helpful in selecting patients' best dialysis methods, and SDM scale results were higher in the peritoneal dialysis group than in the hemodialysis group.
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Fallo Renal Crónico , Diálisis Peritoneal , Masculino , Femenino , Humanos , Persona de Mediana Edad , Diálisis Renal/métodos , Toma de Decisiones Conjunta , Fallo Renal Crónico/terapia , Fallo Renal Crónico/psicología , Encuestas y Cuestionarios , Toma de Decisiones , Participación del Paciente/métodosRESUMEN
BACKGROUND: It is important for the dialysis specialist to provide essential and safe care to hemodialysis (HD) patients. However, little is known about the actual effect of dialysis specialist care on the survival of HD patients. We therefore investigated the influence of dialysis specialist care on patient mortality in a nationwide Korean dialysis cohort. METHODS: We used an HD quality assessment and National Health Insurance Service claims data from October to December 2015. A total of 34,408 patients were divided into two groups according to the proportion of dialysis specialists in their HD unit, as follows: 0%, no dialysis specialist care group, and ≥50%, dialysis specialist care group. We analyzed the mortality risk of these groups using the Cox proportional hazards model after matching propensity scores. RESULTS: After propensity score matching, 18,344 patients were enrolled. The ratio of patients from the groups with and without dialysis specialist care was 86.7% to 13.3%. The dialysis specialist care group showed a shorter dialysis vintage, higher levels of hemoglobin, higher single-pool Kt/V values, lower levels of phosphorus, and lower systolic and diastolic blood pressures than the no dialysis specialist care group. After adjusting demographic and clinical parameters, the absence of dialysis specialist care was a significant independent risk factor for all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.18; p = 0.004). CONCLUSION: Dialysis specialist care is an important determinant of overall patient survival among HD patients. Appropriate care given by dialysis specialists may improve clinical outcomes of patients undergoing HD.
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The brain-targeted delivery of therapeutic oligonucleotides has been investigated as a new treatment modality for various brain diseases, such as brain tumors. However, delivery efficiency into the brain has been limited due to the blood-brain barrier. In this research, brain-targeted exosome-mimetic cell membrane nanovesicles (CMNVs) were designed to enhance the delivery of therapeutic oligonucleotides into the brain. First, CMNVs were produced by extrusion with isolated C6 cell membrane fragments. Then, CMNVs were decorated with cholesterol-linked T7 peptides as a targeting ligand by hydrophobic interaction, producing T7-CMNV. T7-CMNV was in aqueous solution maintained its nanoparticle size for over 21 days. The targeting and delivery effects of T7-CMNVs were evaluated in an orthotopic glioblastoma animal model. 2'-O-metyl and cholesterol-TEG modified anti-microRNA-21 oligonucleotides (AMO21c) were loaded into T7-CMNVs, and biodistribution experiments indicated that T7-CMNVs delivered AMO21c more efficiently into the brain than CMNVs, scrambled T7-CMNVs, lipofectamine, and naked AMO21c after systemic administration. In addition, AMO21c down-regulated miRNA-21 (miR-21) levels in glioblastoma tissue most efficiently in the T7-CMNVs group. This enhanced suppression of miR-21 resulted in the up-regulation of PDCD4 and PTEN. Eventually, brain tumor size was reduced in the T7-CMNVs group more efficiently than in the other control groups. With stability, low toxicity, and targeting efficiency, T7-CMNVs may be useful to the development of oligonucleotide therapy for brain tumors.
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INTRODUCTION: miRNA-21 (miR-21) is highly expressed in glioblastoma, facilitating tumor growth by blocking the expression of apoptosis-related genes. Therefore, an antisense microRNA oligonucleotide (AMO) against miR-21 was suggested as a therapeutic nucleic acid for glioblastoma. OBJECTIVES: AMO21 co-micelles were developed with tumor-targeting T7 peptides as an AMO21 delivery system by intranasal administration. METHODS: Cholesterol-conjugated AMO21 (AMO21c) was mixed with cholesterol-conjugated T7 peptides (T7c) to produce tumor-targeted co-micelles. Physical characterization was performed by dynamic light scattering, gel retardation assay, scanning electron microscope and heparin competition assay. In vitro transfection efficiency to C6 glioblastoma cells was measured by flow cytometry. The AMO21c/T7c co-micelles were administered by intranasal instillation into the brain of intracranial glioblastoma rat models. Scrambled T7 (scrT7) and scrambled AMO21c (scrAMO21c) were used as a negative control. The therapeutic effects of the AMO21c/T7c co-micelles were evaluated by real time RT-PCR, immunohistochemistry, TUNEL assay, and Nissl staining. RESULTS: The formation of the AMO21c/T7c co-micelles was confirmed in gel retardation and heparin competition assays. The highest delivery efficiency in vitro was achieved at a 1:10 wt ratio of AMO21c/T7c. The AMO21c/T7c co-micelles had higher delivery efficiency into C6 glioblastoma cells than naked AMO21c or AMO21c/lipofectamine complexes. After intranasal administration into the intracranial glioblastoma models, the delivery efficiency of the co-micelles into the brain was also higher than those of naked AMO21c and AMO21c/scrambled T7c. Thanks to their enhanced delivery efficiency, the AMO21c/T7c co-micelles downregulated miR-21, inducing the production of the pro-apoptotic phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4) proteins in the tumor tissues. The tumor size was reduced by the AMO21c/T7c co-micelles more effectively than naked AMO21c, AMO21c/lipofectamine, or scrAMO21c/T7c treatment. CONCLUSION: The results suggest that the co-micelles of AMO21c and T7c may be an efficient delivery system into a brain tumor through intranasal administration.
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Glioblastoma , MicroARNs , Ratas , Animales , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Micelas , Oligonucleótidos Antisentido/uso terapéutico , Línea Celular Tumoral , Péptidos/uso terapéutico , Oligonucleótidos/uso terapéutico , MicroARNs/genética , Proteínas Reguladoras de la Apoptosis/uso terapéutico , Colesterol , Heparina/uso terapéuticoRESUMEN
BACKGROUND: Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients. METHODS: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter. RESULTS: The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae. CONCLUSION: Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.
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BACKGROUND: Many countries have their own hemodialysis (HD) quality assurance programs and star rating systems for HD facilities. However, the effects of HD quality assurance programs on patient mortality are not well understood. Therefore, in the present study, the effects of the Korean HD facility star rating on patient mortality in maintenance HD patients were evaluated. METHODS: This longitudinal, observational cohort study included 35,271 patients receiving HD treatment from 741 facilities. The fivestar ratings of HD facilities were determined based on HD quality assessment data from 2015, which includes 12 quality measures in structural, procedural, and outcome domains. The patients were grouped into high (three to five stars) and low (one or two stars) groups based on HD facility star rating. Cox proportional hazards model was used to evaluate the effects of star rating on patient mortality during the mean follow-up duration of 3 years. RESULTS: The patient ratio between high and low HD facility star rating groups was 82.0% vs. 18.0%. The patients in the low star rating group showed lower single-pool Kt/V and higher calcium and phosphorus levels compared with subjects in the high star rating group. After adjusting for sociodemographic and clinical parameters, the HD facility star rating independently increased the mortality risk (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18; p = 0.002). CONCLUSION: The HD facilities with low star rating showed higher patient mortality.
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Malnutrition is common in patients undergoing hemodialysis (HD) and is associated with mortality. This study aimed to investigate the association between changes in nutrition status measured by the Geriatric Nutritional Risk Index (GNRI) and all-cause mortality in patients who started HD. A nationwide retrospective cohort study was conducted based on the Korean Renal Data System database. Patients who started HD from January 2016 to December 2018, and were eligible for GNRI and GNRI trend were included. GNRI trend was a longitudinal change of GNRI, assessed by random slope in a mixed-effect model. Positive and negative random slopes in each patient were assigned to positive and negative GNRI trends. A total of 2313 patients were included and median follow-up period was 3.1 (2.6-3.7) years. GNRI values decreased over time (estimate - 1.212, 95% confidence interval (CI) - 1.116-0.692) and positive GNRI trend was associated with survival benefit (hazard ratio 0.55, 95% CI 0.36-0.84) after multivariate adjustment. These findings show that serial GNRI assessment, besides GNRI, is a useful prognostic factor for mortality in patients who start HD.
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Fallo Renal Crónico , Humanos , Anciano , Fallo Renal Crónico/complicaciones , Evaluación Nutricional , Estudios Retrospectivos , Diálisis Renal/efectos adversos , Sistema de Registros , República de Corea/epidemiologíaRESUMEN
Ischemic stroke is caused by the occlusion of cerebral arteries. In the ischemic stroke, ischemia-reperfusion injury increases the damage in the brain after reperfusion. In the previous study, heme oxygenase-1 (HO1) mRNA was delivered into the ischemic brain, showing that HO1-mRNA had higher therapeutic effect and less side-effect than HO1-plasmid (pHO1). However, mRNA is degraded faster than plasmid DNA reducing the duration of gene expression. In this study, self-replicating mRNA (Rep-mRNA) was developed using a replicon system from Venezuelan Equine Encephalitis virus to compensate this disadvantage of mRNA delivery. Deoxycholic acid-conjugated polyethylenimine (DA-PEI) was used as a carrier of the mRNAs. The Rep-mRNA/DA-PEI complex had a size of around 90 nm and a zeta-potential of 33 mV. In the in vitro transfection assays, gene expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 14 days, while that by the HO1-mRNA/DA-PEI complex approached basal level at 3 days after transfection. Therapeutic effects of the HO1-Rep-mRNA/DA-PEI complexes were evaluated in the ischemic stroke animal model. The complexes were injected into the brain stereotaxically. HO1 expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 7 days after injection, but the pHO1/DA-PEI or HO1-mRNA/DA-PEI complex showed basal level of HO1-expression at 7 days after injection. Due to higher and longer expression of HO1, the apoptosis level and infarct size were decreased by the HO1-Rep-mRNA/DA-PEI complexes, compared with the pHO1/DA-PEI and HO1-mRNA/DA-PEI complex. These results suggest that HO1-Rep-mRNA/DA-PEI complex may have a potential as a long-lasting therapeutic system for the treatment of ischemic stroke.
Asunto(s)
Hemo-Oxigenasa 1 , Accidente Cerebrovascular Isquémico , Animales , Encéfalo , ADN , Ácido Desoxicólico , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/farmacología , Hemo-Oxigenasa 1/uso terapéutico , Polietileneimina/farmacología , ARN Mensajero/genética , ARN Mensajero/farmacologíaRESUMEN
The geriatric nutritional risk index (GNRI) is a nutrition-related risk assessment tool and has been used in various clinical settings. The relationship between body mass index (BMI) and the associated risk of diabetic retinopathy (DR) remains inconclusive. We aimed to evaluate the association between GNRI and DR in patients with type 2 diabetes. We included a total of 1359 patients with type 2 diabetes who followed up in our diabetes clinic and underwent fundus photographic examinations from August 2006 to February 2014. DR was assessed by retinal ophthalmologists using comprehensive ophthalmologic examinations. Patients were divided into tertiles according to their GNRI category. Patients in a lower GNRI tertile tended to have a higher proportion of nonproliferative DR (NPDR) and proliferative DR (PDR) compared with those in the other tertiles. The risk of PDR was higher in patients included in GNRI tertile 1 (Odds ratio (OR) 2.252, 95% Confidence Interval (CI) 1.080-4.823, P = 0.033) and GNRI tertile 2 (OR 2.602, 95% CI 1.323-5.336, P = 0.007) compared with those in GNRI tertile 3. In patients with lower GNRIs, the prevalence of DR was higher than in those with higher GNRIs. When GNRI was compared with BMI using the area under the curve, overall accuracy was high in GNRI. The risk of PDR was high in patients with low GNRI and there is an inverse association between GNRI scores and prevalence of DR. GNRI might be a useful tool to predict DR in patients with type 2 diabetes.