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AIM: We studied the effects of overhydration (OH), Kt/Vurea and ß2-microglobulin (ß2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD). METHODS: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis ß2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality. RESULTS: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis ß2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis ß2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis ß2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and ß2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality. CONCLUSION: Higher OH/ECW, higher predialysis ß2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD.
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Biomarcadores , Enfermedad de la Arteria Coronaria , Diálisis Renal , Calcificación Vascular , Microglobulina beta-2 , Humanos , Masculino , Femenino , Diálisis Renal/efectos adversos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Microglobulina beta-2/sangre , Calcificación Vascular/epidemiología , Calcificación Vascular/mortalidad , Biomarcadores/sangre , Factores de Riesgo , Desequilibrio Hidroelectrolítico/epidemiología , Desequilibrio Hidroelectrolítico/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Urea/sangreRESUMEN
AIM: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD). METHODS: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed. RESULTS: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05). CONCLUSION: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality.
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Enfermedad de la Arteria Coronaria , Modelos de Riesgos Proporcionales , Diálisis Renal , Calcificación Vascular , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Calcificación Vascular/sangre , Calcificación Vascular/mortalidad , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/sangre , Anciano de 80 o más Años , Factores de Tiempo , Ferritinas/sangre , Factores de Riesgo , Biomarcadores/sangre , Anemia Ferropénica/mortalidad , Anemia Ferropénica/sangre , Anemia Ferropénica/diagnóstico , Transferrina/análisis , Transferrina/metabolismo , Estudios Prospectivos , Resultado del Tratamiento , Medición de Riesgo , Prevalencia , Modelos LinealesRESUMEN
BACKGROUND: Arteriovenous fistula (AVF) patency is important for patients undergoing hemodialysis. The association between early AVF failure and the prognosis, including all-cause mortality and major adverse cardiovascular events (MACE), has not been fully investigated. The present study was performed to investigate the association between early AVF failure and 3-year mortality, cardiovascular disease (CVD) mortality, and MACE. METHODS: We analyzed 358 patients who started hemodialysis in our institution from October 2008 to February 2020. We defined early AVF failure as cases requiring percutaneous transluminal angioplasty or reoperation within 1 year after AVF surgery. The patients were divided into two groups according to the presence or absence of early AVF failure, and the prognosis of each group was examined. The association between early AVF failure and outcomes (3-year all-cause mortality, CVD mortality, and MACE) was determined using Cox proportional hazards regression analysis. RESULTS: During the 3-year follow-up, 75 (20.9%) patients died (cardiovascular death: n = 39) and 145 patients developed MACE. According to the multivariable analysis, the early AVF failure group had a significantly higher risk of 3-year all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09-1.83; p = 0.009), CVD mortality (HR, 1.54; 95% CI, 1.29-2.08; p < 0.001), and MACE (HR, 1.68; 95% CI, 1.25-2.26; p < 0.001). When the patients were stratified by age, early AVF failure was associated with 3-year all-cause mortality in all groups except for the younger group (<65 years of age). CONCLUSIONS: Early AVF failure was associated with an increased risk of 3-year all-cause mortality, CVD mortality, and MACE.
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AIM: ß2-Microglobulin (ß2-MG) and α1-microglobulin (α1-MG) have molecular weights of 11,800 and 33,000 Da, respectively. We studied the α1-MG and ß2-MG reduction ratios (RRs) and survival in patients on predilution online haemodiafiltration (Pre-OL-HDF). METHODS: Participants were 247 Pre-OL-HDF patients. α1-MG and ß2-MG RRs were assessed at baseline. Kaplan-Meier survival and Cox proportional hazard analyses were used. RESULTS: In 247 patients, the median age was 67 (56-73) years, the dialysis duration was 77 (46-150) months, and the diabetes prevalence was 47.4%. Twenty-two patients died over the 450-day study period. The mortality cut-off values using receiver-operating characteristic curves for the α1-MG and ß2-MG RRs were 20% and 80%, respectively. Survival rates were significantly (p < 0.05) higher in patients with α1-MG RRs ≥20% (n = 134) compared with patients with α1-MG RRs <20% (n = 113) and in patients with ß2-MG RRs ≥80% (n = 87) compared with patients with ß2-MG RRs <80% (n = 160). Cox models adjusting for diabetes and dialysis duration showed that α1-MG RR, ß2-MG RR, and pre- and postdialysis ß2-MG were risk factors for all-cause mortality; however, after additional adjustment for age, sex, and serum albumin, only ß2-MG RR and pre- and postdialysis ß2-MG were significant predictors of mortality (p < 0.05). α1-MG RRs were significantly correlated with ß2-MG RRs (ρ = 0.73, p < 0.0001) and serum albumin levels (ρ = 0.13, p < 0.05). CONCLUSION: In patients on Pre-OL-HDF, α1-MG RRs ≥20% and ß2-MG RRs ≥80% were associated with better survival, ß2-MG RR ≥80% and pre-and postdialysis ß2-MG levels were significant predictors of all-cause mortality, and α1-MG RR ≥20% may predict mortality.
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Hemodiafiltración , Anciano , Humanos , Microglobulina beta-2/análisis , Hemodiafiltración/efectos adversos , Estudios Prospectivos , Diálisis Renal , Albúmina Sérica , Persona de Mediana Edad , Globinas alfa/análisisRESUMEN
The optical Freedericksz transition (OFT) can reversibly control the molecular orientation of liquid crystals (LCs) only by light irradiation, leading to the development of all-optical devices, such as smart windows. In particular, oligothiophene-doped LCs show the highly sensitive OFT due to the interaction between dyes and an optical-electric field. However, the sensitivity is still low for the application to optical devices. It is necessary to understand the factors in LCs affecting the OFT behavior to reduce the sensitivity. In this study, we investigated the effect of the host LC structure on the OFT in oligothiophene-doped LCs. The threshold light intensity for the OFT in trifluorinated LCs was 42% lower than that in LCs without fluorine substituents. This result contributes to the material design for the low-threshold optical devices utilizing the OFT of dye-doped LCs.
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This study aimed to investigate whether a combined estimation of the geriatric nutritional risk index (GNRI) and the modified creatinine index (mCI) provides synergistic information for mortality in patients treated by chronic hemodialysis. We analyzed 499 patients on hemodialysis for five years. We set each cut-off value as the high (≥92) and low (<92) GNRI groups and the high (≥21 mg/kg/day) and low (<21 mg/kg/day) mCI groups, and divided them into four subgroups: G1, high GNRI + high mCI; G2, high GNRI + low mCI; G3, low GNRI + high mCI; and G4, low GNRI + low mCI. The survival rate was evaluated and time-to-event analysis was performed. All-cause death occurred in 142 (28%) patients. Kaplan−Meier curves showed that G2 and G4 had a significantly worse outcome (p < 0.05) than G1 but not G3. Using the multivariable-adjusted model, only G4 was significantly associated with all-cause mortality compared with G1. Our study suggests that the synergistic effects of the GNRI and the mCI are helpful in predicting all-cause mortality. The combination of these indices may be superior to a single method to distinguish patients who are well or moderately ill from potentially severely ill.
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Fallo Renal Crónico , Desnutrición , Anciano , Creatinina , Evaluación Geriátrica/métodos , Humanos , Fallo Renal Crónico/terapia , Desnutrición/complicaciones , Evaluación Nutricional , Estado Nutricional , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
INTRODUCTION: We investigated the association between intradialytic hypotension (IDH) and coronary artery calcification and their effects on mortality in hemodialysis (HD) patients. METHODS: Consecutive patients undergoing maintenance HD were enrolled. The study timeline included the baseline (day 1), exposure assessment (day 1-day 22), and outcome assessment (day 23-3 years) periods. IDH was defined as a nadir systolic blood pressure (SBP) of <100 mmHg or vasopressor use during at least 2 of 10 HD sessions in the exposure assessment period. The clinical data at baseline and the Agatston coronary artery calcium score (CACS) were assessed in the exposure assessment period. FINDINGS: The median age and dialysis vintage were 67 years [60-75 years] and 73 months [37-138 months], respectively. IDH occurred in 37 patients (21.4%), and the CACS was higher in the IDH group than in the non-IDH group (p = 0.08). IDH was associated with CACS, diabetes mellitus, mean predialysis SBP, and mean ultrafiltration volume (p < 0.05). The cutoff CACS for mortality was 1829 (sensitivity: 69%, specificity: 77%). In all, 45 all-cause deaths and 19 cardiovascular deaths occurred over 3 years. Patients with both IDH and a CACS of ≥1829 had a lower 3-year cumulative survival from cardiovascular death (66.7%) than those with a CACS of ≥1829 (80.3%), IDH (88.5%), or neither (95.5%) (p < 0.01). IDH, a CACS of ≥1829, and IDH + CACS of ≥1829 were predictors of 3-year all-cause and cardiovascular mortality (p < 0.05). The hazard ratio for cardiovascular mortality was highest in the group with IDH + CACS ≥ 1829. DISCUSSION: A high CACS may be a biomarker for IDH. Both IDH and CACS were risk factors for all-cause and cardiovascular mortality in patients undergoing HD, and there was a synergistic interaction between IDH and high CACS for cardiovascular mortality.
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Hipotensión , Fallo Renal Crónico , Presión Sanguínea , Vasos Coronarios , Humanos , Hipotensión/etiología , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: The CHA2DS2-VASc score has been widely used to predict stroke in patients with atrial fibrillation (AF). Recently, it was reported that the CHA2DS2-VASc score helps predict cardiovascular disease (CVD) or all-cause mortality in patients with or without AF. However, few reports have examined the association between this score and mortality in hemodialysis (HD) patients. METHODS: We analyzed 557 consecutive patients who initiated HD at our facilities between February 2005 and October 2017. The CHA2DS2-VASc score was calculated at the time of initiation of HD. Patients were then categorized into three groups according to their CHA2DS2-VASc scores: 0-1 (low), 2-3 (intermediate), and 4-9 (high). Multivariate Cox proportional hazards analysis was used to assess independent risk factors for 3-year all-cause mortality. RESULTS: During the 3-year follow-up period, 153 (27.5%) patients died (cardiovascular death: n = 88). According to multivariate analysis, serum albumin (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43-0.85, p = 0.003), creatinine (HR 0.91, 95% CI 0.84-0.99, p = 0.049), and CHA2DS2-VASc score (HR 1.33, 95% CI 1.20-1.46, p < 0.001) were associated with 3-year all-cause mortality. Compared with patients in the low CHA2DS2-VASc score group, those in the intermediate- and high-score groups had a higher risk for all-cause and CVD mortality (all-cause mortality: HR 1.77, 95% CI 1.23-2.55, p = 0.002 and HR 2.94, 95% CI 1.90-4.53, p < 0.001, respectively; CVD mortality: HR 1.82, 95% CI 1.27-2.59, p = 0.001 and HR 2.85, 95% CI 1.88-4.31, p < 0.001, respectively). CONCLUSION: The CHA2DS2-VASc score is a valuable predictor of 3-year all-cause and CVD mortality in incident HD patients.
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Fibrilación Atrial , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Humanos , Pronóstico , Diálisis Renal/efectos adversos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/etiologíaRESUMEN
AIM: The effect of convection volume (CV) in patients on pre-dilution online haemodiafiltration (Pre-OL-HDF) was evaluated. METHODS: We conducted a retrospective, cross-sectional study in 126 patients on Pre-OL-HDF. Dialysis conditions, laboratory data, and same day post-dialysis body composition measurements using bioimpedance spectroscopy were assessed. Patients were divided into two groups according to their CV: ≥ median value and < median value. Linear regression analyses for reduction ratios (RRs) of ß2-microglobulin and α1-microglobulin, and body composition, were conducted. RESULTS: Age, dialysis vintage, and CVs of the study patients were 64 ± 12 years, 81 (48-154) months, and 43.2 (38.5-55.9) L/session, respectively. The higher CV (≥ 43 L/session) group (n = 66) had significantly higher RRs of ß2-microglobulin and α1-microglobulin, lean tissue index, body cell mass index, total body water (TBW), extracellular water (ECW), and intracellular water (ICW) compared with the lower CV (< 43 L/session) group (n = 60, p < .01). Serum albumin and fat tissue index were not significantly different between the groups. CV/ECW, CV/TBW, and CV/ICW but not un-adjusted CV, were significant determinants for ß2-microglobulin and α1-microglobulin RRs (p < .05). Lean tissue and body cell mass indexes, but not the fat tissue index, showed significant associations with CV, and RRs of ß2-microglobulin and α1-microglobulin (p < kb.05). CONCLUSIONS: Among patients on Pre-OL-HDF, higher values in the lean tissue index and body cell mass index were observed in those with higher CV versus lower CV, and CV adjusted to body water may be useful to prescribe individualized conditions for Pre-OL-HDF.
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Hemodiafiltración , Anciano , Composición Corporal , Convección , Estudios Transversales , Hemodiafiltración/efectos adversos , Hemodiafiltración/métodos , Humanos , Persona de Mediana Edad , Diálisis Renal/métodos , Estudios Retrospectivos , AguaRESUMEN
Optical limiting is a phenomenon widely recognized as the potential application for a protector of human eyes and optical sensors from irradiation with lasers. However, a high optical limiting threshold and low flexibility have restricted such applications. Here, we report that oligothiophene-doped liquid crystals (LCs) function as a low-threshold optical limiter with deformability. Irradiation of dye-doped LCs with a continuous wave (CW) laser beam brings about the formation of diffraction rings, and the number of rings changes depending on the incident light intensity due to their photoinduced molecular reorientation. Utilizing such reorientation enables reversible optical limiting without additional multilayered optical components. In particular, an electric field application to a LC-based optical limiter decreases their optical limiting threshold from 2100 to 25 mW/cm2, and the threshold can be tuned by adjusting the applied voltage. Furthermore, the softness of LCs allows for the fabrication of the deformable optical limiter; optical limiting due to the molecular reorientation occurs even in largely bent states. The low-threshold and deformable optical limiter based on oligothiophene-doped LCs thus will enable one to develop the protector of eyes and optical sensors from glaring light-induced damage.
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OBJECTIVE: A high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients. METHODS: We studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston's CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted. RESULTS: The median (interquartile range) age and duration of dialysis of the participants were 67 (60-75) years and 73 (37-138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05). CONCLUSION: We have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.
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Enfermedad de la Arteria Coronaria/epidemiología , Hierro/sangre , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/terapia , Calcificación Vascular/epidemiología , Anciano , Causas de Muerte , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Femenino , Ferritinas/sangre , Ferritinas/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hierro/metabolismo , Masculino , Persona de Mediana Edad , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Transferrina/análisis , Transferrina/metabolismo , Calcificación Vascular/sangre , Calcificación Vascular/etiología , Calcificación Vascular/patologíaRESUMEN
AIM: Assess the association and predictive value of geriatric nutritional risk index (GNRI), body composition, and bone mineral density (BMD) in haemodialysis (HD) patients. METHODS: Laboratory data, body composition parameters measured via body composition monitor, and radius, lumbar spine, femoral neck BMD measured using dual energy X-ray absorptiometry were assessed in all subjects on HD or online haemodiafiltration (HDF) at baseline. Regression analysis for GNRI, Cox proportional hazard analyses and comparison of multiple receiver operating characteristic (ROC) curves were performed. RESULTS: Among all 264 patients, age was 65 ± 12 years and dialysis vintage was 79 (39-144) months. GNRI tertile (T)1, T2, and T3 were 88 (85-91), 94 (93-95), and 98 (97-101), respectively. Patients in GNRI T1 had lower fat tissue index (FTI), lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD, but higher overhydration/extracellular fluid than patients in GNRI T2 or T3 (P < .05). GNRI was significantly associated with FTI, lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD (P < .01). GNRI was a significant predictor of 2-year all-cause mortality (HR 0.92, P < .05). Area under the ROC curve for all-cause mortality using traditional risk factors (age, sex, diabetes mellitus, cardiovascular disease, use of vasopressors for dialysis-related hypotension, and C-reactive protein) was 0.67 and changed by adding GNRI (0.78, P < .05), FTI (0.75), or femoral neck BMD (0.66), respectively. CONCLUSION: Associations between GNRI, body composition, and BMD were confirmed in HD patients. Combining GNRI with traditional risk factors improved mortality prediction in HD patients.
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Composición Corporal , Densidad Ósea , Evaluación Geriátrica , Evaluación Nutricional , Diálisis Renal , Anciano , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de RiesgoRESUMEN
INTRODUCTION: A relationship between serum magnesium (Mg) and body composition parameters has not been reported in hemodialysis (HD) patients. We aimed to clarify whether serum Mg has any association with body composition parameters, or survival in HD patients. METHODS: This study included 215 consecutive maintenance HD patients. Laboratory data collection and postdialysis body composition analysis were performed at baseline. The patients were divided based on baseline serum Mg level tertiles (low, medium, and high Mg groups). Kaplan-Meier survival, logistic regression analyses and Cox proportional hazard analyses were conducted. FINDINGS: Among all patients, the median age and dialysis vintage were 73 (65-81) years and 44 (8-96) months, respectively. The serum Mg levels were < 2.3, 2.3-2.5, and > 2.5 mg/dL for the low (n = 67), middle (n = 76), and high (n = 72) Mg groups, respectively. Compared to other groups, low Mg group showed significantly higher age and C-reactive protein levels, but lower serum albumin, normalized protein catabolic rates and frequency of on-line hemodiafiltration. The low, middle, and high Mg groups differed significantly regarding body cell mass (fat-free mass without bone mineral mass and extracellular water) index (BCMI): [5.6 (4.2-6.8), 6.0 (4.8-8.1), 6.7 (4.9-7.5) kg/m2 , respectively] and overhydration/extracellular water ratio (OH/ECW) [11.7 (4.5-21.9), 4.8 (1.0-14.1), 8.5 (-0.5-15.0) %, respectively] but not regarding body mass index, lean tissue index, fat tissue index. Hypomagnesemia was significantly associated with BCMI [odds ratio (OR) [95% confidence interval (CI)]: 0.85 [0.73-1.00] and OH/ECW (OR [95% CI]: 1.03 [1.01-1.05]), respectively. Kaplan-Meyer 3-year survival rates were 53.6%, 69.7%, and 71.7% in low, middle, and high Mg groups, respectively. However, hypomagnesemia was not significantly associated with 3-year all-cause mortality independent of age, serum albumin and C-reactive protein. DISCUSSION: Hypomagnesemia was associated with lower BCMI, more pronounced OH/ECW and poorer Kaplan-Meier 3-year cumulative survival, but was not an independent risk factor for mortality in HD patients.
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Composición Corporal/efectos de los fármacos , Magnesio/sangre , Diálisis Renal/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Diálisis Renal/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Objective: This study evaluated associations of serum matrix Gla protein (MGP), plasma vitamin K1, and plasma vitamin K2 with coronary artery calcium score (CACS) and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods: Subjects comprised 112 MHD patients aged 30-60 years and 40 age-matched healthy subjects. Total MGP, vitamin K1, vitamin K2, and lipid profile were examined in all subjects; other clinical data, medication use, and CACS were assessed only in MHD patients. Determinants of MGP in all subjects were identified by regression analysis. Factors associated with CACS and CVD in MHD patients were identified by regression analysis and logistic analysis, respectively. Results: Lower plasma levels of vitamin K1 corrected for triglycerides [0.39 (0.24-0.70) vs. 0.77 (0.48-1.34) ng/mg, p < 0.001], higher frequency of plasma vitamin K2 ≤ 0.05 ng/ml (p = 0.23), and higher serum total MGP (288.4 ± 44.2 vs. 159.7 ± 40.6 ng/ml, p < 0.0001) were observed in MHD patients than in healthy controls. Total MGP level was significantly associated with levels of vitamin K1 corrected for triglycerides (p <0 .001) and vitamin K2 ≤ 0.05 ng/ml (p < 0.05) in all subjects. Total MGP level was significantly associated with presence of CVD (p <0 .05), but not CACS, in MHD patients. Conclusion: The end-stage renal disease on hemodialysis is a deficiency state of vitamin K. Total MGP was significantly higher in MHD patients compared to healthy subjects and total MGP was associated with the presence of CVD, but not CACS, in MHD patients.
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Proteínas de Unión al Calcio/sangre , Proteínas de la Matriz Extracelular/sangre , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Calcificación Vascular/epidemiología , Vitamina K/sangre , Adulto , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Calcificación Vascular/sangre , Calcificación Vascular/etiología , Proteína Gla de la MatrizRESUMEN
PURPOSE: It is unclear whether hypomagnesemia is an independent risk factor or innocent bystander for mortality in maintenance hemodialysis (MHD) patients. Thus, we studied associations between hypomagnesemia and all-cause as well as cardiovascular (CV) mortality in MHD patients. METHODS: Baseline clinical characteristics and coronary artery calcium score (CACS) of 353 Japanese MHD patients were reviewed. Three-year survival rate and mortality risk factors were assessed. RESULTS: Median (interquartile range) age, dialysis vintage, serum magnesium (Mg), serum albumin and CACS of the subjects were 68 (60-78) years, 75 (32-151) months, 2.4 (2.2-2.7) mg/dl, 3.6 (3.3-3.8) g/dl, and 1181 (278-3190), respectively. During the 3-year period, 91 patients died. Kaplan-Meier overall 3-year survival rates were 59.0% in in patients with Mg < 2.4 mg/dl (n = 136) and 82.3% in patients with Mg ≥ 2.4 mg/dl (n = 217), (P < 0.0001). In Cox regression models not incorporating serum albumin, Mg < 2.4 mg/dl was significantly associated with 3-year all-cause death, independent of age, dialysis vintage, average ultrafiltration, Log (CACS + 1), warfarin use, serum potassium, high-sensitivity C-reactive protein (hsCRP), phosphate, uric acid, and intact parathyroid hormone [Hazard ratio (HR) 95% confidence interval (CI): 2.82 (1.31-6.29), P = 0.0078], and CV death, independent of age, dialysis vintage, Log (CACS + 1), warfarin use, serum hsCRP, and uric acid [HR (95% CI): 4.47 (1.45-16.76), P = 0.0086]. Nevertheless, associations of Mg < 2.4 mg/dl with all-cause and CV mortality were all absent in models that included serum albumin. CONCLUSIONS: Hypomagnesemia is not an independent risk factor for mortality but is associated with malnutrition in MHD patients.
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Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Magnesio/sangre , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/mortalidad , Diálisis Renal , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning.
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Condicionamiento Palpebral/fisiología , Receptores Muscarínicos/metabolismo , Animales , Condicionamiento Palpebral/efectos de los fármacos , Aprendizaje Discriminativo/efectos de los fármacos , Aprendizaje Discriminativo/fisiología , Electromiografía , Masculino , Ratones , Ratones Endogámicos C57BL , Antagonistas Muscarínicos/farmacología , Escopolamina/farmacologíaRESUMEN
BACKGROUND: A low level of intact parathyroid hormone (PTH) is an indicator of adynamic bone disease in hemodialysis patients, and is associated with a significant increase of all-cause mortality. Thus, effective treatment for adynamic bone disease is required. We previously investigated the effect of vitamin K2 on adynamic bone disease. In this study, we assessed the efficacy of oral vitamin K2 in a controlled trial. METHODS: Forty hemodialysis patients with low intact PTH levels (<100 pg/ml) were randomly divided into two groups, which were a vitamin K2 group receiving oral menatetrenone (45 mg/day) for 1 year and a control group without vitamin K2. Venous blood samples were collected at baseline and during the study for measurement of bone metabolism parameters. RESULTS: Thirty-three patients completed follow-up. There was a significant increase of the serum intact osteocalcin level after 1 month of vitamin K2 administration. Serum levels of intact PTH, bone alkaline phosphatase, and cross-linked N-terminal telopeptide of type I collagen increased significantly after 12 months in the vitamin K2 group. The serum osteoprotegerin level was decreased after 12 months in the vitamin K2 group, but the change was not significant. CONCLUSION: Vitamin K2 therapy improves bone remodeling in hemodialysis patients with a low intact PTH level.
Asunto(s)
Enfermedades Óseas/etiología , Enfermedades Óseas/metabolismo , Hormona Paratiroidea/sangre , Diálisis Renal/efectos adversos , Vitamina K 2/análogos & derivados , Anciano , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Remodelación Ósea/efectos de los fármacos , Colágeno Tipo I/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Péptidos/sangre , Estadísticas no Paramétricas , Vitamina K 2/farmacología , Vitamina K 2/uso terapéuticoRESUMEN
Introduction of ZIP family transporter gene homologues TjZnt1 and TjZnt2 (metal ion transporters) into yeast strains conferred increased Ni(II) tolerance in that species. The action of ZIP family transporter homologues, however, could not explain the Ni resistance of yeast strains transformed with TjZnt1 and TjZnt2. To elucidate the mechanism of Ni tolerance conferred by TjZnt1 and TjZnt2 in yeast strains, we made a series of investigations based upon three hypotheses, including (1) cellular Ni efflux, (2) exclusion of Ni due to competitive uptake of other metals, and (3) Ni binding to histidine-rich domains (chelation). The critical Ni tolerance level of TjZnt2 expressing yeast strains was 1.4mM, whereas, the TjZnt1 expressing yeast strains were tolerant of Ni concentrations as high as 2.0mM. The TjZnt1 expressing yeast strain had significantly lower Ni content and significantly higher Zn content than the control and TjZnt2 expressing yeast strain. Effects of the deletion of histidine-rich domain HRD1 or HRD2, or deletion of the region from HRD1 to HRD2, resulted in the same or slightly less Ni(II) tolerance in the TjZnt1 expressing yeast strain. These data indicate that Ni tolerance of the TjZnt2 expressing yeast strain is not correlated with binding to HRDs (Hypothesis 3). Ni tolerance of TjZnt1 expressing yeast strain was, however, partially correlated with Zn influx, which suppressed Ni influx, therefore Ni influx (Hypothesis 1) and competitive inhibition of Ni influx by other metals (Hypothesis 2), remain viable hypotheses which will be subject to further testing.
Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Níquel/metabolismo , Níquel/farmacología , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte de Catión/genética , Tolerancia a Medicamentos , Expresión Génica , Genes de Plantas/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estructura Terciaria de Proteína/genética , Saccharomyces cerevisiae/efectos de los fármacos , Zinc/metabolismoRESUMEN
Ni homeostasis is essential for plant cell activity, but the mechanisms of Ni-transport and delivery are unknown. To elucidate the role of ZIP and NRAMP metal-transporters for Ni2+-transport and homeostasis, we cloned their homologous genes from the Ni hyperaccumulator Thlaspi japonicum, and investigated their Ni-transporting abilities by expression in yeast. The deduced amino acid sequences of the two Zip transporter genes (TjZnt1, TjZnt2) and one Nramp transporter gene cloned had high homologies with TcZNT1 and TcZNT2 of Thlaspi caerulescens and AtNRAMP4 of Arabidopsis thaliana, respectively, and were predicted as integral membrane proteins with 6 or 12 transmembrane domains. TjZNT1 and TjZNT2 had two long histidine-rich domains in the putative cytoplasmic domain between transmembrane domains III and IV. TjNRAMP4 conserved a consensus transporter motif between transmembrane domains VIII and IX. The yeast transformed with TjZNT1 or TjZNT2 showed a marked increase in Ni2+ tolerance with the gene expression. In contrast, the expression of TjNramp4 caused elevation of Ni2+ sensitivity and Ni2+ concentration. These data suggest that ZIP/NRAMP transporters participate in Ni2+ homeostasis of Ni hyperaccumulator plants. TjZNT1 had Zn2+-, Cd2+- and Mn2+-transporting abilities and TjZNT2 also had Zn2+- and Mn2+-transporting abilities, but TjNRAMP4 could transport Ni2+ but not Zn2+, Cd2+ or Mn2+.
Asunto(s)
Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Níquel/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Thlaspi/genética , Thlaspi/metabolismo , Secuencia de Aminoácidos , Cadmio , Clonación Molecular , Transporte Iónico , Datos de Secuencia Molecular , Filogenia , Saccharomyces cerevisiae/genética , Homología de Secuencia de AminoácidoRESUMEN
BACKGROUND: Synthesis of nitric oxide by endothelial nitric oxide synthase (ENOS) plays a key role in the atherosclerotic process. Several polymorphisms of the gene encoding ENOS are now known and have been investigated with respect to their influence on cardiovascular disease risk in the general population. The authors prospectively investigated whether ENOS gene polymorphisms determined the risk of cardiovascular complications in a cohort of hemodialysis patients. METHODS: A total of 335 nondiabetic hemodialysis patients were genotyped for 3 ENOS polymorphisms (T-786-->C, intron 4, and Glu298Asp polymorphism) and were followed up prospectively for a mean of 44.2 +/- 9.0 months. The end-points of the study were major cardiac, cerebrovascular, or peripheral vascular events. RESULTS: Two ENOS polymorphisms were associated with cardiovascular events: a T to C substitution at position -786 of the promoter and a deletion-insertion in intron 4 (the a allele having 4 repeats of a consensus sequence and the b allele having 5 repeats). A total of 84 subjects were -786C carriers (CC+TC), and 15 (18%) suffered from cardiovascular events compared with only 13 of 251 TT patients (5%). The relative risk of cardiovascular events was higher for -786C carriers compared with noncarriers (relative risk: 2.05, P = 0.0003). It was also higher for a allele carriers (intron 4 polymorphism) compared with noncarriers (relative risk: 1.97, P = 0.0005). CONCLUSION: T-786-->C polymorphism and intron 4 polymorphism, but not Glu298Asp polymorphism, of the ENOS gene can influence the risk of cardiovascular events in Japanese nondiabetic hemodialysis patients.