Diminishing dry weight is strongly associated with all-cause mortality among long-term maintenance prevalent dialysis patients.

OBJECTIVES: To investigate the relationship between dry weight (DW) change and survival in long-term maintenance prevalent dialysis patients. METHODS: We conducted a prospective data collection study with retrospective analysis of the registered data. Patients were followed up for 5 years (1-year observation of DW changes and subsequent 4-year follow-up). The outcome was all-cause mortality. The predictors were 1-year DW change rates. The hazard ratios (HRs) for all-cause mortality were calculated using multivariable Cox regression analysis, fully adjusted for age, sex, basal kidney disease, dialysis vintage, current smoking, past cardiovascular events, serum albumin, DW at enrollment, serum creatinine, mean predialysis systolic blood pressure, and cardiothoracic ratio or 1-year cardiothoracic ratio change rate. Propensity score (PS) analysis was also conducted using the same covariates of Cox regression analysis. RESULTS: In total, 899 dialysis patients (mean dialysis vintage: 101.2 months) were followed up, and 180 deaths were recorded, of which 90 were of cardiovascular origin. Each 2% decrement of DW showed adjusted HR, and the 95% confidence interval was 1.24 [1.16-1.33]. According to the 1-year DW change rate, participants were divided into five groups (group A, ≥+3%; group B, +1 to +2.9%; group C, -0.9 to +0.9%; group D, -2.9 to -1.0%; and group E, ≤-3%). For survival curves based on grouping, group B had the best and group E had the worst survival rate (p<0.01, log-rank test). Therefore, we set group B as a reference; adjusted risks for death of groups D and E were 2.16 [1.23-3.79] and 2.66 [1.54-4.58], respectively. However, this relation was blunted in patients of heavier DW. The PS-matched cohort showed a poorer prognosis in patients with diminishing DW divided by DW change rate at -0.635% (mean value of DW change rate). CONCLUSION: In the long-term maintenance hemodialysis cohort, 1-year DW decrement, especially ≤-3.0%, was significantly associated with all-cause mortality, and cardiovascular disease-related death was prominent in these patients.

N-terminal-pro-B-type-natriuretic peptide associated with 2-year mortality from both cardiovascular and non-cardiovascular origins in prevalent chronic hemodialysis patients.

N-terminal-pro-B-type-natriuretic peptide (NT-proBNP) was a predictive marker of cardiovascular disease (CVD)-related death in chronic dialysis patients. NT-proBNP was also correlated with markers of inflammation, malnutrition and protein-energy wasting. We hypothesized whether NT-proBNP was also associated with non-CVD death in chronic dialysis patients. A prospective observational study for incidence of death in chronic dialysis patients was conducted. Prevalent chronic dialysis patients (n = 1310) were enrolled and followed for 24 months. One hundred forty-four deaths were recorded. Area under the curve using ROC analysis for NT-proBNP showed: all causes of death (0.761), CVD-related (0.750), infection and malignancy-related (0.702) and others and unknown (0.745). After adjusting for age, sex, hemodialysis vintage, cardiothoracic ratio, mean pre-dialysis systolic blood pressure, dry weight and basal kidney disease, the hazard ratios (95% confidence intervals) per 1-log NT-proBNP calculated using multivariate Cox analysis were: all causes of death, 3.83 (2.51-5.85); CVD-related, 4.30 (2.12-8.75); infection and malignancy-related, 2.41 (1.17-4.93); and others and unknown origin, 5.63 (2.57-12.37). NT-proBNP was significantly associated not only with CVD-relate but also with non-CVD-related deaths in this population of prevalent chronic dialysis patients.

Risk of Cerebral Infarction in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study (MID study).

BACKGROUND/AIMS: Predictors including the preventive effects of antiplatelet and anticoagulant drugs on cerebral infarction (CI) events have not yet been clarified in dialysis patients. The aim of the present study was to examine the risk of CI and preventive effects of these drugs in Japanese hemodialysis patients. METHODS: Patients receiving maintenance hemodialysis (n=1,551, median age (interquartile range), 69.0 (59.0-78.0) years; 41.5% female) were enrolled in the Miyazaki Dialysis Cohort Study and prospectively followed-up for 3 years. Kaplan-Meier and Cox's regression analyses were used to clarify the risk of CI. RESULTS: Eighty-four patients developed CI at an incidence of 21.5/1000 patients per year. The presence of a previous history of CI, atrial fibrillation (AF), and diabetes mellitus in addition to age were also identified as predictive factors for new CI, whereas no relationship was observed between antiplatelet and/or anticoagulant usage and CI. Furthermore, no significant difference was noted in the frequency of CI events between patients with AF who received warfarin and those who did not. CONCLUSIONS: The incidence of CI was higher in dialysis patients with a previous history of CI and AF; however, the preventive effects of antiplatelet/anticoagulant drugs on the development of CI were not evident.

Apoprotein B/Apoprotein A-1 Ratio and Mortality among Prevalent Dialysis Patients.

BACKGROUND AND OBJECTIVES: In dialysis patients, the associations between apoprotein profile and all-cause or cardiovascular disease (CVD)-related mortality are not well known. We, therefore, investigated whether apoprotein levels are associated with these events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We undertook a prospective observational cohort study of prevalent hemodialysis patients aged ≥18 years (n=1081), who were followed for 4 years (2011-2014). Outcomes were all-cause and CVD-related mortality. Predictors used were baseline apoprotein levels, particularly the apoprotein B (apo B)/ apoprotein A-1 (apo A-1) ratio. A Cox regression analysis was used to calculate the hazard ratios (HRs) for mortality. Apo A-1, apo B, and apo B/ apo A-1 ratio were analyzed with adjustments in three models: model 1, basic adjustment for age and sex; model 2, basic adjustments plus dialysis conditions (dialysis vintage, mean predialysis systolic blood pressure, dry weight, and mean intradialytic weight gain); and model 3, model 2 plus metabolic and inflammatory conditions (basal kidney disease, serum albumin, C-reactive protein level, and statin use). RESULTS: Of the 1081 patients included in the study, 203 deaths were recorded, 92 of which were related to CVD. The apo B/ apo A-1 ratio was significantly associated with all-cause and CVD-related mortality when analyzed by 1-SD increments or quartile IV versus I in all models. In model 3, HRs and 95% confidence intervals (95% CIs) for 1-SD increments of apo B/ apo A-1 ratio for all-cause mortality or CVD-related mortality were: HR, 1.16 (95% CI, 1.00 to 1.35), or HR, 1.38 (95% CI, 1.11 to 1.71), respectively, and for quartile IV versus I: HR, 1.65 (95% CI, 1.05 to 2.57), or HR, 2.56 (95% CI, 1.21 to 5.40), respectively. Apo A-1 was significantly associated with both mortalities in models 1 and 2. However, apo B was only significantly associated with CVD-related mortality in model 3. CONCLUSIONS: Apoprotein measurement, especially the apo B/ apo A-1 ratio, was significantly associated with all-cause and CVD-related mortality in prevalent dialysis patients.

Glycaemic control is a predictor of infection-related hospitalization on haemodialysis patients: Miyazaki Dialysis Cohort study (MID study).

AIM: Although infection is the second leading cause of death in maintenance haemodialysis patients, the effects of glycaemic control on infection in diabetic haemodialysis patients have not yet been examined in detail. We examined the relationship between diabetes or glycemic control and infection-related hospitalization (IRH) in haemodialysis patients. METHODS: Patients receiving maintenance haemodialysis (n = 1551, 493 diabetic patients) were enrolled in this prospective cohort study in December 2009 and followed-up for 3 years. IRH during the follow-up period was abstracted from medical records. Kaplan-Meier and Cox regression analyses were used to investigate the relationship between diabetes or glycaemic control and IRH. RESULTS: The Kaplan-Meier analysis revealed that the risk of IRH was significantly higher in haemodialysis patients with diabetes, particularly in those with poorly controlled HbA1c levels (HbA1c ≥ 7.0%), than in haemodialysis patients without diabetes. When patients with ≥HbA1c 7.0% were divided into two groups using a median value of HbA1c, the risk of IRH was significantly higher in those with the poorest glycaemic control (HbA1c ≥ 7.4%), an older age, or lower albumin levels. The multivariable-adjusted hazard ratio for the risk of IRH was not higher in the second criteria of HbA1c (HbA1c 7.0-7.3%), but was significantly higher in the group with the poorest glycaemic control (HbA1c ≥ 7.4%) than in those in the good control criterion (HbA1c < 7.0%). CONCLUSIONS: Although diabetes is a risk factor for IRH among maintenance haemodialysis patients, the relationship between glycaemic control and the risk of infection is not linear. Therefore, the risk of infection may increase in a manner that is dependent on the glycaemic control threshold.

Evaluation of a new bio-impedance spectroscopy device in healthy Japanese.

BACKGROUND: The use of a new bio-impedance spectroscopy device (Body Composition Monitor, BCM) in the field of dialysis became possible in Japan. However, it is unknown whether the data obtained using this apparatus are indicative for Japanese dialysis patients. OBJECTIVE: To compare individual fluid status in healthy Japanese using the BCM device with the data obtained from healthy Caucasians. METHODS: A total of 219 volunteers (female vs. male, 150 vs. 69; mean age, 68.8 ± 8.4 years; mean BMI, 22.6 ± 2.9 kg/m2) were enrolled. The measurement was performed by the end of the morning before exercise. RESULTS: Mean over-hydration (OH) level was 0.7 ± 0.8 L. Nearly 80% of subjects had values equivalent to the standard values of healthy Caucasians (-1.1∼1.1 L). Age had a weak positive correlation to OH. The fat tissue index levels were slightly lower in Japanese than in Caucasians. On the other hand, the levels of lean tissue index and ECW/ICW (E/I) ratio did not differ between Japanese and Caucasians. E/I ratio showed a good correlation with OH level. CONCLUSION: Fluid status of healthy Japanese was equivalent to the standard value of Caucasians. Although validity of using parameters from healthy Caucasians in healthy Japanese population was considered to be confirmed, validity of use in Japanese dialysis patients should be evaluated further using the parameters from healthy Caucasians.

[Clinical characteristics of patients with IgA nephropathy and long-term survival after dialysis therapy].

BACKGROUND AND OBJECTIVES: Little is known about the treatment and clinical status of patients with biopsy-proven IgA nephropathy (IgAN) during long-term maintenance dialysis. METHODS: Fifty-two of 433 patients with IgAN who had favorable survival rates of 93.3% and 65.1% at 10 and 20 years, respectively, in a previous study and had reached end-stage kidney disease were followed up for 11.1 ± 6.2 years. Forty of the 52 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) at the final observation in February 2012 were eligible for entry in this study. Laboratory findings, treatments and complications during the long-term follow-up were analyzed. RESULTS: Mean age at starting dialysis (HD, n = 39; PD, n = 1) was 44.2 ± 13.1 years. Vascular access was achieved through an arteriovenous fistula in 95% of the 39 patients. Prescription rates of anti-hypertensive agents (68%), anti-platelet agents (35%), and statins (15%) were relatively low. The cardiothoracic ratio was well-controlled (< 50%) in about 60% of all patients and mean values for hemoglobin (10.6 ± 1.31 g/dL), adjusted calcium (9.56 ± 0.81 mg/dL), phosphate(5.89 ± 1.64 mg/dL), and intact-PTH (186 ± 221 pg/mL) were within the treatment goals recommended by Japanese guidelines. Complications during follow-up comprised cardiovascular events (n = 11), malignancy (n = 4), diabetes (n = 2), and arterial fibrillation (n = 2). Patients who remained on dialysis for > 10 years (n = 22) had started dialysis when they were significantly younger, and had a higher rate of onset of malignancy and of intact PTH values than those who were on dialysis for < 10 years (n = 18). CONCLUSIONS: Patients with IgAN who remain on dialysis over the long-term can maintain stable and favorable clinical findings although the occurrence of malignant complications and bone mineral metabolic disorder should be monitored.

Long-term survival of patients with IgA nephropathy after dialysis therapy.

BACKGROUND/AIMS: How dialysis affects the survival of patients with biopsy-proven IgA nephropathy (IgAN) is not fully understood. The present long-term cohort study quantifies the survival rates and incidence of cardio-cerebrovascular diseases (CCVDs) among such patients in Japan. METHODS: Fifty-two of 433 patients with IgAN who had reached end-stage kidney disease underwent renal replacement therapy (RRT) between 1981 and 2010. The overall survival rate and incidence of CCVDs in these patients were evaluated during follow-up for 11.3 ± 6.4 years. RESULTS: The mean age at starting RRT was 42.8 ± 13.3 years. Only seven patients died during follow-up (mortality rate, 1.2/100 person-years) and Kaplan-Meier analysis revealed favorable survival rates of 93.3% and 65.1% at 10 and 20 years, respectively, compared with that of patients with glomerulonephritis in the registry of the Japanese Society for Dialysis Therapy who required RRT. Malignancy and CCVDs were causes of death at 13.6 ± 4.8 and 3.9 ± 1.3 years, respectively, after starting RRT. Fatal and non-fatal CCVDs developed in 15 (incidence, 2.7/100 person-years) patients and acute coronary syndrome and cerebral hemorrhage developed relatively soon after starting RRT. Cox proportional hazards models revealed that age at the time of starting RRT was a significant factor affecting the onset of CCVDs. Meanwhile, a history of having had corticosteroid as an initial treatment did not affect the onset of events. CONCLUSION: Although the survival of patients with IgAN is favorable after dialysis, the onset of CCVDs during the early phase of dialysis should be carefully monitored.

Allylation of alcohols and carboxylic acids with allyl acetate catalyzed by [Ir(cod)2](+)BF4- complex.

A facile method for the synthesis of allyl alkyl ethers from alcohols with allyl acetate was developed by the use of [Ir(cod)(2)](+)BF(4)(-) complex. For instance, the reaction of allyl acetate with n-octyl alcohol in the presence of a catalytic amount of [Ir(cod)(2)](+)BF(4)(-) complex afforded allyl octyl ether in quantitative yield. Allyl carboxylates were also prepared by the exchange reaction between carboxylic acids and allyl acetate in good yields. The [Ir(cod)(2)](+)BF(4)(-) complex catalyzed the reaction of alkyl and aromatic amines with allyl acetate to lead to the corresponding allylamines in fair to good yields.

An efficient direct alpha-alkylation of ketones with primary alcohols catalyzed by [Ir(cod)Cl]2/PPh3/KOH system without solvent.

alpha-Alkylation of ketones was successfully achieved by the reaction of ketones with alcohols catalyzed by iridium complexes in the presence of a small amount of base. For example, 2-octanone was allowed to react with butanol under the influence of [Ir(cod)Cl]2/PPh3/KOH to give 6-dodecanone in good yield. The reaction was found to proceed by using a 1:1 mixture of ketone and alcohol without use of any solvent.

Head-to-tail dimerization of acrylates catalyzed by iridium complexes.

Head-to-tail dimerizations of acrylates and vinyl ketone were successfully performed by the use of iridium complexes in good yields. An iridium hydride complex generated in situ from [IrCl(cod)]2 and alcohols in the presence of Na2CO3 and (MeO)3P was found to be an active species promoting the head-to-tail dimerization of acrylates. Thus, butyl acrylate afforded the corresponding head-to-tail dimer in 86% yield.