A survey of environmental sustainability in Japanese dialysis facilities.

BACKGROUND: Dialysis practice has a particularly high environmental impact, including responsible for carbon emissions and climate change. Insufficient research has been conducted on environmental sustainability activities in dialysis therapy in Japan. METHODS: We conducted an online Green Survey comprising 30 question items based on a previously conducted survey in Australia. Between August and September 2023, this was sent to members of the Japanese Association of Dialysis Physicians, including hospital and clinic physicians, working across 885 dialysis facilities in Japan. RESULTS: In total, 255 (29%) facilities responded to the survey. More than half of the facilities (n = 157; 61.6%) responded that they did not have a strategy, policy, or action plan for environmental sustainability. In four-fifths of the facilities (n = 208; 81.6%), no "green team" or committee had been formed to promote environmental protection. By contrast, most of the surveyed facilities had emergency strategies for natural disasters, such as covering for patient visits and staff commuting during extreme weather conditions (n = 169; 66.3%), water shortages (n = 159; 62.4%), and power outages (n = 188; 73.7%). CONCLUSIONS: Following the UK, Australia and New Zealand, and Portugal, this is the fourth Green Survey to be conducted, and the first on environmental sustainability among kidney health-care providers in Japan. The results indicated that daily activities for environmental protection are still lacking at many facilities, even though the management of dialysis treatment during a natural disaster is well conducted.

Total iron binding capacity is a predictor for muscle loss in maintenance hemodialysis patients.

BACKGROUND: Protein-energy wasting in hemodialysis (HD) patients is characterized by decreased skeletal muscle mass and plasma protein. Some previous studies reported relationships between skeletal muscle dysfunction and iron deficiency. Dialysis patients with malnutrition may have a functional iron deficiency (FID) because of inflammation. Serum total iron binding capacity (TIBC), correlated with transferrin, is a nutritional status marker in HD patients and a biomarker of iron status. The relationship between muscle loss and iron status is unknown. The aim of the present study was to assess the relationship between iron status and change in skeletal muscle mass. METHODS: A prospective cohort of 267 HD patients was examined for 12 months. Blood samples were obtained at baseline to measure TIBC, ferritin, transferrin saturation (TSAT), and hepcidin-25. Nutritional status and changes in muscle mass were assessed by subjective global assessment, albumin, creatinine index, and percentage creatinine generation rate. RESULTS: At baseline, lower tertiles of TIBC were significantly related to lower muscle mass and albumin levels; they were also significantly correlated with high ferritin, hepcidin-25, and TSAT levels, as well as a higher proportion of use of erythropoiesis-stimulating agents. Multiple regression analysis adjusted with confounders showed TIBC was an independent biomarker for decreased muscle mass and albumin. Change in muscle mass remained significantly decreased in the lower tertile of TIBC and in malnourished patients. CONCLUSIONS: The present study demonstrated relationships between FID and muscle loss. TIBC was an independent biomarker of muscle loss in HD patients, considering iron status, inflammation, oxidative stress, and malnutrition.

Truncal Adiposity Influences High-Density Lipoprotein Cholesterol Levels and Cardiovascular Events in Hemodialysis Patients.

OBJECTIVE: Adiposity influences lipid metabolism and atherosclerotic cardiovascular disease (CVD) in the general population. The aim of the present study was to assess the association between fat mass (FM) and lipid metabolism and CVD events among patients on hemodialysis (HD). METHODS: This prospective observational study examined 240 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, and adiponectin. Lipids and hs-CRP were measured every 3 months for 12 months. FM was estimated by dual energy x-ray absorptiometric scan at baseline and 12 months later. Patients were then prospectively followed up for 36 months after the 1-year measurement period, and composite CVD events were estimated. RESULTS: Truncal FM was positively correlated with body mass index, hs-CRP, interleukin-6, total cholesterol, low-density lipoprotein-C, triglyceride, and negatively correlated with high-density lipoprotein (HDL)-C and adiponectin at baseline. HDL-C levels were repeatedly decreased, and triglyceride and non-HDL-C were serially increased in the patient group with truncal FM > 7,000 g at both baseline and 12 months (large truncal FM group) compared with the other groups. Cox proportional hazards models adjusted for confounders showed composite CVD events occurred significantly in patients with large truncal FM and continuous low HDL-C levels. CONCLUSIONS: Truncal adiposity influences lipid metabolism in patients on HD, and the prevalence of CVD events may be increased in those patients with high fat and lipid abnormalities, especially continuously low HDL-C levels.

Active vitamin D analogs, maxacalcitol and alfacalcidol, as maintenance therapy for mild secondary hyperparathyroidism in hemodialysis patients - a randomized study.

BACKGROUND: The present randomized study was designed to compare the efficacy between two active vitamin D analogs, alfacalcidol (ACD) and maxacalcitol (OCT), for the management of mild secondary hyperparathyroidism (SHPT) in dialysis patients. METHODS: SHPT in all 32 patients analyzed in the study was initially treated with OCT. Once patients' intact PTH levels decreased to the target range of 150 - 180 pg/mL, they were randomized either to switch to ACD at 0.5 µg/day (n = 14), or to remain on an effectively unchanged dose of OCT (n = 13). Phosphate, calcium, and intact PTH levels were measured every 2 weeks for 12 weeks and vitamin D doses were changed according to target ranges of phosphate (3.5 - 6.0 mg/dL), calcium (albuminadjusted calcium: 8.4 - 10.0 mg/dL), and intact parathyroid hormone (60 - 180 pg/mL). Achievement rates of the target ranges of the parameters were estimated. RESULTS: Baseline calcium levels in the OCT group were significantly higher than in the ACD group. Changes in achievement rates of target ranges of intact PTH and calcium during the study did not differ significantly between the vitamin D drugs. Changes in calcium levels in the OCT and ACD groups were similar during the study. Achievement rates of the target range of phosphate in both groups were also similar until 8 weeks, although the rate in the OCT group declined at 10 weeks. CONCLUSIONS: The efficacy and safety of OCT for the treatment of mild SHPT are similar to those of ACD in hemodialysis patients.

Employment rates for working-age patients receiving hemodialysis increasing: Changing economic environment.

INTRODUCTION: This study explored employment trends among working-age patients undergoing hemodialysis using 5-year surveys from 1996 to 2021. Policy changes affecting individuals with disabilities, the economic environment, and employment status among the general population in Japan were considered. Differences in trends by gender and health status were examined. METHODS: Employment status was categorized into employment and nonemployment; and regular, nonregular, and self. Analytical data with similar characteristics were generated over the six surveys using the propensity score method. RESULTS: The employment rate, especially among women, increased from 1996 to 2021. However, the employment rate ratio to the general population was approximately 80% for men and 50% for women, even in 2021. The employment rate increased with an expansion in nonregular employment. Women's employment trends could be explained by changes in real gross domestic product and employment quotas for individuals with disabilities. CONCLUSION: Employment trends differ by gender and by regular versus nonregular employment.

Influence of dialysis-related stigma on health-related indicators in Japanese patients undergoing hemodialysis.

INTRODUCTION: Focusing on impacts to health-related indicators in older Japanese patients, this study analyzed both the direct influence of dialysis-related stigma and influences of its intersectionality with other stigmatized characteristics. METHODS: Data were collected through a cross-sectional survey of 7461 outpatients in dialysis facilities. Other stigmatized characteristics include lower income, lower education, disabled activities of daily living, and diabetic end-stage renal disease (ESRD) as a cause for starting dialysis treatment. RESULTS: The average rate of an "agree" response on dialysis-related stigma items was 18.2%. Dialysis-related stigma significantly influenced all three health-related indicators, including suspected depression, informal networks, and compliance with dietary therapy. In addition, each interaction between dialysis-related stigma and educational attainment, gender, and diabetic ESRD significantly influence one health-related indicator. CONCLUSION: These results suggest that dialysis-related stigma has both a significant direct and synergic influence with other stigmatized characteristics on health-related indicators.

Long-Term Effect of Denosumab on Bone Disease in Patients with CKD.

BACKGROUND: The effect of long-term denosumab therapy and of denosumab discontinuation on the cortical bone of the hip regions in dialysis patients has not been studied. METHODS: This retrospective study investigated the cortical and trabecular compartments and estimated strength indices of the hip region, obtained using 3D-SHAPER software, after a maximum of 5 years of denosumab therapy in 124 dialysis patients. A Wilcoxon signed-rank test was used to identify the differences in each parameter before and after denosumab initiation. Similarly, we investigated the changes in these parameters after denosumab discontinuation in 11 dialysis patients. RESULTS: Integral and trabecular volumetric bone mineral densities (BMD) were significantly lower at the start of denosumab therapy than those in 1 year before denosumab initiation. After starting denosumab, areal BMD (median change +7.7% [interquartile range (IQR), +4.6 to +10.6]), cortical volumetric BMD (median change +3.4% [IQR, +1.0 to +4.7]), cortical surface BMD (median change +7.1% [IQR, +3.4 to +9.4]), and cortical thickness (median change +3.2% [IQR, +1.8 to +4.9]) showed a significantly higher trend for 3.5 years, which then stabilized at a higher value compared with baseline. A similar trend in the trabecular volumetric BMD (median change +9.8% [IQR, +3.8 to +15.7]) was observed over 2.5 years, with a higher value maintained thereafter. The whole area of the hip region improved after denosumab therapy. Similar trajectories were also found in the estimated strength indices. Conversely, at 1 year after denosumab discontinuation, these 3D parameters and estimated strength indices tended to largely worsen. The lateral aspect of the greater trochanter was the most pronounced location showing volumetric BMD loss. CONCLUSIONS: The BMD of both cortical and trabecular components in the hip region was significantly higher after starting denosumab therapy. However, these measurements exhibited a trend of declining substantially after the discontinuation of denosumab.

Number of enlarged parathyroid glands might be a predictor of cinacalcet response in advanced secondary hyperparathyroidism.

BACKGROUND: Cinacalcet has been shown to be effective in lowering serum intact parathyroid hormone (iPTH) levels in patients with advanced secondary hyperparathyroidism (SHPT). We investigated clinical factors influencing therapeutic response to cinacalcet for SHPT refractory to active vitamin D sterols. METHODS: A total of 57 hemodialysis patients with SHPT (iPTH >300 pg/mL) were enrolled in this 28-week, prospective, observational study. Cinacalcet was started at an initial dose of 25 mg/day; the dose of cinacalcet was titrated to achieve the following: 3.5 ≤ phosphate (P) ≤ 6.0 mg/dL; 8.4 ≤ adjusted calcium (Ca) ≤ 10.0 mg/dL; 60 ≤ iPTH ≤ 180 pg/mL). Parathyroid ultrasonographic examination was performed at the start of cinacalcet treatment. Patients were divided into two groups on the basis of iPTH levels after 28 weeks: Group A, iPTH ≤180 pg/mL; Group B, iPTH >180 pg/mL. RESULTS: Serum iPTH and P levels at baseline were significantly higher in Group B than Group A. The number of enlarged parathyroid glands (PTGs) (estimated volume ≥500 mm(3) or major axis ≥10 mm), which presumably had nodular hyperplastic lesions, and the largest and the total volume of detectable PTGs were significantly greater in Group B compared with Group A. In our multivariate logistic regression analysis, patients with two or more enlarged PTGs had a significant risk of poor response to cinacalcet treatment (odds ratio 5.68, 95% confidence interval 1.19-32.66, P = 0.0363). CONCLUSION: These results indicate that the number of enlarged PTGs could predict therapeutic response of cinacalcet in patients with advanced SHPT.

Influences of Financial Strains Over the Life Course Before Initiating Hemodialysis on Health Outcomes Among Older Japanese Patients: A Retrospective Study in Japan.

PURPOSE: This study analyzed the influence of financial strains over the life course before initiating hemodialysis on the health outcomes of older Japanese patients. This study was limited to financial strains over the life course before initiating hemodialysis to eliminate the influence of financial strains resulting from resignation from paid jobs. We examined which of the four life course models-pathway, latent, social mobility, and accumulation-were appropriate to describe the influences of financial strains over the life course on older patients' health. PATIENTS AND METHODS: Data were obtained from a cross-sectional survey of 6,644 outpatients in dialysis facilities across Japan. We selected participants aged 60 years and older at the time of the survey. Numbers of dialysis complications, activities of daily living (ADL) disability, and depressive symptoms were selected as health outcomes. Benchmark periods over the life course were constructed in three parts: less than 18 years (childhood), 18-35 years (young adults), and 35-50 years (middle-aged). We retrospectively measured financial strains over the life course. RESULTS: Pathway models best described the influence of financial strains over the life course on the three types of health outcomes. Experiences of financial strains as young adults had a direct influence on ADL disability of older patients. This result supports latent models. Social mobility models (upward and downward mobility) and accumulation models explained the number of dialysis complications, ADL disability, and depressive symptoms in older patients. CONCLUSION: These results suggest that socioeconomic disadvantages over the life course before initiating hemodialysis were significantly associated with health outcomes in older patients.

Discordance between hemodialysis patients' reports and their physicians' estimates of adherence to dietary restrictions in Japan.

INTRODUCTION: This study examined the discordance between hemodialysis patients' reports and their physicians' estimates of dietary restriction adherence and related factors in Japan. METHODS: In a cross-sectional survey of 6644 outpatients, physicians who estimated higher and lower adherence than their patients' self-reported were categorized as overestimation and underestimation in terms of discordance, respectively. Possible factors included clinical indicators, patient characteristics related to negative stereotypes, and health beliefs related to statistical discrimination. RESULTS: The concordance rate was 0.069 based on the weighted kappa coefficient. The coefficients of acceptable serum potassium, prevalence of diabetes, and self-efficacy on overestimates were 0.663, -0.126, and -0.132, respectively. The coefficients of these factors on underestimates were -0.589, 0.338, and 0.145, respectively. All these coefficients were significant. CONCLUSIONS: The discordance may be high and is related to physicians' clinical data reliance, negative stereotypes about patient characteristics, and a lack of understanding of patients' health beliefs.

Assessment of inflow of endotoxin and its fragments in patients on maintenance hemodialysis.

BACKGROUND: We estimated the flow of endotoxins (ET) from dialysates into the blood of patients on hemodialysis (HD) using limulus amebocyte lysate (LAL) assays and endotoxin activity (EA) determined by neutrophil respiratory burst activity. METHODS: A cross-sectional study compared groups given ultrapure bicarbonate (n = 15; group A), acetate-free bicarbonate dialysates (n = 20; group B) and conventional bicarbonate dialysate (n = 23; group C). A prospective study of group C examined the effect of changing the purity of the dialysate. Biomarkers of inflammation and oxidative stress were measured and ET in blood was assessed by LAL assays and EA. RESULTS: Serum ET levels did not differ among the groups, whereas EA and the biomarkers were significantly increased in group C compared with those in groups A and B. HD using conventional dialysate was independently associated with an increase in EA. Purifying the dialysate significantly decreased EA in group C. CONCLUSION: Measuring EA is useful to assess the influence of dialysate contamination in HD patients.

Bone density of the femoral neck in patients on maintenance dialysis.

BACKGROUND: Our institution recently started using the femoral neck (FN), as well as the non-shunted distal radius (Rd), to measure bone mineral density (BMD) in patients with chronic kidney disease. We examined the utility and characteristics of this measurement in patients on maintenance dialysis. METHODS: We selected 293 patients on chronic dialysis. We measured Rd and FN BMD using dual-energy X-ray absorptiometry, and we reviewed blood test findings, which included hemoglobin, albumin, blood urea nitrogen, creatinine, adjusted calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone. We conducted a multiple linear regression analysis that was stratified according to sex, age, body weight, height, and dialysis vintage. The Rd and FN BMD values were the dependent variables, and the blood test findings were the independent variables. We compared the areas under the curve (AUCs) of Rd and FN BMD using receiver operating characteristic curve analysis to differentiate between patients with and without fractures. RESULTS: FN BMD was significantly lower than Rd BMD. The general risk factors for osteoporosis, such as low body weight, older age, muscle mass loss, and malnutrition, influenced FN BMD. FN and Rd BMD were not correlated with calcium, phosphorous, or intact parathyroid hormone, whereas a significant, negative correlation with alkaline phosphatase was detected. Both men and women with a history of fragility fractures had significantly lower Rd and FN BMDs than patients without such a history. However, there was no significant difference between the AUCs of FN and Rd BMD for fractures in both men and women. CONCLUSIONS: FN BMD was significantly lower than Rd BMD. Additionally, FN BMD was not inferior to Rd BMD for assessing the risk of fracture in patients on maintenance dialysis.

Effects of 22-oxacalcitriol and calcitriol on PTH secretion and bone mineral metabolism in a crossover trial in hemodialysis patients with secondary hyperparathyroidism.

The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.

High fibroblast growth factor 23 levels are associated with decreased ferritin levels and increased intravenous iron doses in hemodialysis patients.

A recent study demonstrated the association between inflammation, iron metabolism and fibroblast growth factor (FGF) 23. The present clinical study aimed to assess associations between anemia, iron metabolism and FGF23 in hemodialysis (HD) patients. This prospective observational study examined a cohort of prevalent HD patients (n = 282). Blood samples were obtained before dialysis sessions to measure baseline levels of hemoglobin (Hb), transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact (i)-FGF23, high sensitive (hs)-CRP, and interleukin-6. After the baseline measurement, study patients were followed-up for 6 months. Biochemical measurements were subsequently performed at 1 (Hb), 2 (TSAT and ferritin) or 3 (Ca, P and hs-CRP) month intervals. Doses of ESAs and intravenous iron supplementation during the study period were recorded. i-FGF23 was positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin. However, levels of Hb and hs-CRP and doses of ESAs during the study period did not differ among the i-FGF23 tertiles, with levels of ferritin and TSAT in the higher i-FGF23 tertile being consistently lower than in the middle to lower i-FGF23 tertiles. Multivariate repeated measures analysis indicated that the higher i-FGF23 tertile was independently associated with repeated measurements of ferritin, but not of TSAT. Doses of intravenous iron supplementation were significantly increased in the higher i-FGF23 tertile in multivariate models. In conclusion, high i-FGF23 levels may be associated with prolongation of low levels of ferritin, resulting in increased usages of iron supplementation in HD patients.

Clinical Effectiveness of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared with Predilution On-Line Hemodiafiltration.

BACKGROUND: In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment. SUMMARY: A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of ß2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.

Apolipoproteins are associated with survival among patients on hemodialysis (HD), but these associations might be influenced by dysfunctional (oxidized) high-density lipoprotein (HDL). We assessed associations among apolipoproteins and oxidized HDL, mortality and cardiovascular disease (CVD) events in patients on HD. This prospective observational study examined 412 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, apolipoproteins, oxidized LDL, oxidized HDL, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 at baseline, and HDL-C and hs-CRP were measured 12 months later. Patients were then prospectively followed-up (mean, 40 months) and all-cause mortality and composite CVD events were analyzed. Associations between variables at baseline and clinical outcome were assessed by Cox proportional hazards modeling (n = 412) and Cox hazards modeling with a time-varying covariate with HDL-C and hs-CRP (n = 369). Quartiles of apolipoproteins and oxidized HDL were not associated with all-cause mortality. However, Cox proportional hazards models with quartiles of each variable adjusted for confounders and hs-CRP or IL-6 identified apolipoprotein (apo)B-to-apoA-I ratio (apoB/apoA-I) and oxidized HDL, but not apoA-I or apoA-II, as independent risk factors for composite CVD events. These associations were confirmed by Cox proportional hazards modeling with time-varying covariates for hs-CRP. ApoB/apoA-I was independently associated with composite CVD events in 1-standard deviation (SD) increase-of-variables models adjusted for the confounders, oxidized HDL and hs-CRP. However, these associations disappeared from the model adjusted with IL-6 instead of hs-CRP, and oxidized HDL and IL-6 were independently associated with composite CVD events. Findings resembled those from Cox proportional hazards modeling using time-varying covariates with HDL-C adjusted with IL-6. In conclusion, both oxidized HDL and apoB/apoA-I might be associated with CVD events in patients on prevalent HD, while associations of apoB/apoA-I with CVD events differed between models of apoB/apoA-I quartiles and 1-SD increases, and were influenced by IL-6.

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Loss of Muscle Mass in Prevalent Hemodialysis Patients.

Protein-energy wasting (PEW) is common in hemodialysis (HD) patients. A recent study demonstrated that a high level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be associated with PEW in those patients. This prospective study aimed to assess the association of NT-proBNP with body composition and muscle loss. A cohort of prevalent HD patients (n = 238) was examined. Blood samples were obtained at baseline to measure high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin and NT-proBNP. Nutritional status and changes in muscle mass were assessed by subjective global assessment, percentage creatinine generation rate (%CGR), creatinine index (CI) and lean body mass (LBM) estimated by dual-energy X-ray absorptiometry (DXA). The %CGR and CI were calculated five times for one year, and DXA was performed at baseline and one year later. Cardiac function was estimated by ultrasonography at baseline. NT-proBNP was significantly higher in HD patients with PEW. High NT-proBNP was associated with cardiac dysfunction, increased levels of hsCRP and IL-6, and serially decreased levels of the indexes for muscle mass. Multiple regression analysis adjusted with confounders showed that NT-proBNP was an independent predictor for decrease in LBM and serial lower levels of %CGR and CI. In conclusion, the present study demonstrated a novel association between NT-proBNP and muscle loss. NT-proBNP may be an independent biomarker for malnutrition in HD patients, especially in patients with muscles loss, regardless of chronic inflammation, cardiac dysfunction, or overhydration.

Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management.

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.

Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients.

BACKGROUND AND OBJECTIVES: Here, we assessed the impact of oxidized high-density lipoprotein (oxHDL), dysfunctional HDL, on mortality and cardiovascular disease (CVD) events in prevalent HD patients and compared oxHDL to interleukin-6 (IL-6), a strong predictor of CVD events in HD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This prospective study examined a cohort of prevalent HD patients (n=412). Blood samples were obtained at baseline to measure lipids, high-sensitive C-reactive protein (hsCRP), IL-6, oxidized low-density lipoprotein, N-terminal pro B-type natriuretic peptide, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase, adiponectin, and oxHDL. Carotid intima-media thickness (CIMT) was assessed at baseline and 3-year follow-up. Nutritional status was assessed by subjective global assessment (SGA), body mass index, and geriatric nutritional risk index (GNRI). After the baseline assessment, study patients were prospectively followed up (mean observational period, 40 months). RESULTS: At baseline, patients with high oxHDL had a worse nutritional state and higher HDL-cholesterol (HDL-chol), ICAM-1, and adiponectin levels and a higher oxHDL/HDL-chol ratio than low oxHDL patients. A combination of high oxHDL and high IL-6 was significantly associated with increased CIMT at baseline and a larger increase in CIMT at 3-year follow-up. High oxHDL did not predict all-cause mortality; however, it was significantly associated with CVD-related mortality and composite CVD events, particularly with concomitant high IL-6. These associations were confirmed in multivariate Cox hazard models adjusted with confounding variables. CONCLUSIONS: High oxHDL, particularly with concomitant high IL-6, may be associated with an increased risk of CVD events and CVD-related mortality in prevalent HD patients.