[Roles of and Team Medical Care Involving Clinical Engineers in Blood Purification Therapy].

Progress in medical care strongly depends on the development of pharmaceutical and medical technologies. Multi-disciplinary care by a medical team is required for the diversity of medical care. "Clinical engineering technician (CET) " is one of the national medical licenses in Japan. Many CETs are engaged in blood purification therapies. Team medical care, involving medical doctors, nurses, CETs, etc., in the hemodialysis field is useful for the early detection of complications in dialysis patients and provision of appropriate treatments. In some medical facilities, for example, progressive approaches such as appropriate nutritional guidance by a dietitian or exercise therapy by a physical therapist are practiced in advance. Clinical laboratory technologists (CLTs), furthermore, play an important role in team medical care for dial- ysis therapy. They can use ultrasonic equipment for vascular access management. Based on the results of the ABI and SPP measurements by CLTs, medical doctors can diagnose PAD in dialysis patients. [Review].

Differences in the Characteristics of Dialysis Patients in Japan Compared with Those in Other Countries.

BACKGROUND: Japanese patients undergoing dialysis have an extremely low mortality rate compared with those in the United States and Europe. As shown in the Dialysis Outcomes 38; Practice Patterns Study (DOPPS), certain features of dialysis treatment, such as single treatment time and amount of blood flow, are unique to Japan, but factors contributing to the low mortality risk are unclear. Although DOPPS is a multi-country prospective cohort study, the study results may not entirely reflect the real trend in Japan because the number of Japanese institutions participating in the study is small. SUMMARY: In this article, we review the data reported for Japan and other countries and reveal country-specific differences, particularly in patient age distribution and duration of dialysis. KEY MESSAGES: The mean age of prevalent dialysis patients is rising every year in Japan, and the proportion of patients undergoing dialysis for long periods of time is also increasing. In addition, the proportion of dialysis patients with diabetes, one of the primary diseases, has increased to a level similar to that observed in Western countries. However, no significant decline in the crude death rate among prevalent dialysis patients has been observed in Japan, presumably because of technological advances in dialysis treatment, but further studies are needed to elucidate the contributing factors.

Associations among epoetin therapy, inflammation, nutritional status, and mortality in patients on hemodialysis.

OBJECTIVE: Inflammation contributes to hemopoiesis by lowering responses to epoetin (EPO) and to an increase in the mortality of patients on hemodialysis. However, nutritional status might alter associations among inflammation, EPO responsiveness, and the risk of mortality. We assessed the effect of inflammation on mortality according to nutritional status among EPO responses in a cohort of prevalent hemodialysis patients. DESIGN AND METHODS: The observational cohort study analyzed data from the Japanese Dialysis Registry (2005-2006; n = 36,956; mean follow-up 11.5 months). Patients were categorized into tertiles of the EPO responsiveness index (ERI; the weekly weight-adjusted EPO dose [IU/kg/week] divided by hemoglobin [g/dL]) and an EPO-free group. Body mass index (BMI) and C-reactive protein (CRP) levels were measured. RESULTS: Bimodal peaks indicated associations between CRP and BMI in each group. Hazard ratio (HR) curves of CRP for mortality according to BMI in the upper ERI tertile, particularly among those with diabetes mellitus (DM), were reverse J-shaped. However, HR curves in the other groups were increased below a threshold BMI of 21 kg/m(2). These associations were confirmed in propensity score-matched populations. CONCLUSION: Risk of CRP for death is apparently changed by BMI in hemodialysis patients with a lower EPO response, especially in those with DM.

Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence.

Oxidative damage and clustering of band 3 in the membrane have been implicated in the removal of senescent human erythrocytes from the circulation at the end of their 120 day life span. However, the biochemical and mechanistic events leading to band 3 cluster formation have yet to be fully defined. Here we show that while neither membrane peroxidation nor methemoglobin (MetHb) formation on their own can induce band 3 clustering in the human erythrocytes, they can do so when acting in combination. We further show that binding of MetHb to the cytoplasmic domain of band 3 in peroxidized, but not in untreated, erythrocyte membranes induces cluster formation. Age-fractionated populations of erythrocytes from normal human blood, obtained by a density gradient procedure, have allowed us to examine a subpopulation, highly enriched in senescent cells. We have found that band 3 clustering is a feature of only this small fraction, amounting to ∼0.1% of total circulating erythrocytes. These senescent cells are characterized by an increased proportion of MetHb as a result of reduced nicotinamide adenine dinucleotide-dependent reductase activity and accumulated oxidative membrane damage. These findings have allowed us to establish that the combined effects of membrane peroxidation and MetHb formation are necessary for band 3 clustering, and this is a very late event in erythrocyte life. A plausible mechanism for the combined effects of membrane peroxidation and MetHb is proposed, involving high-affinity cooperative binding of MetHb to the cytoplasmic domain of oxidized band 3, probably because of its carbonylation, rather than other forms of oxidative damage. This modification leads to dissociation of ankyrin from band 3, allowing the tetrameric MetHb to cross-link the resulting freely diffusible band 3 dimers, with formation of clusters.

Patient selection and prescription of on-line HDF in Japan.

Renal replacement therapy for end-stage kidney disease can be achieved by several interventions including hemodialysis (HD), hemodiafiltration (HDF), peritoneal dialysis (PD) and kidney transplantation, and others. The December 31, 2011 prevalent population included 270,072 patients on HD, 9,094 on PD and 14,051 on HDF; the total treated ESRD population thus rose above 300,000. In contrast, the number of HDF patients decreased after 2007, one of the reasons for Japan's health insurance system. On-line HDF patients were preferentially selected because of their younger age, longer vintage and their lower clinical comorbidity conditions than HD or off-line HDF patients. However, on-line HDF was approved by Japan's health insurance system in 2012. Owing to this approval the number of on-line HDFs may increase in the future.

The C-terminus of the G protein α subunit controls the affinity of nucleotides.

The C-terminus of the G protein α subunit has a well-known role in determining the selective coupling with the cognate G protein-coupled receptor (GPCR). In fact, rhodopsin, a prototypical GPCR, exhibits active state [metarhodopsin II (MII)] stabilization by interacting with G protein [extra formation of MII (eMII)], and the extent of stabilization is affected by the C-terminal sequence of Gα. Here we examine the relationship between the amount of eMII and the activation efficiency of Gi mutants whose Giα forms have different lengths of the C-terminal sequence of Goα. The results show that both the activation efficiencies of Gi and the amounts of eMII were affected by mutations; however, there was no correlation between them. This finding suggested that the C-terminal region of Gα not only stabilizes MII (active state) but also affects the nucleotide-binding site of Gα. Therefore, we measured the activation efficiency of these mutants by MII at several concentrations of GDP and GTP and calculated the rate constants of GDP release, GDP uptake, and GTP uptake. These rate constants of the Gi mutants were substantially different from those of the wild type, indicating that the replacement of the amino acid residues in the C-terminus alters the affinity of nucleotides. The rate constants of GDP uptake and GTP uptake showed a strong correlation, suggesting that the C-terminus of Giα controls the accessibility of the nucleotide-binding site. Therefore, our results strongly suggest that there is a long-range interlink between the C-terminus of Giα and its nucleotide-binding site.

Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center.

OBJECTIVE: We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib. METHODS: Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients. RESULTS: Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters. CONCLUSIONS: Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.

Correlation of new bone metabolic markers with conventional biomarkers in hemodialysis patients.

BACKGROUND: New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients. METHODS: One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study. RESULTS: Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH . CONCLUSION: Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

Characteristics of body composition and nutritional status in patients receiving hemodialysis therapy for more than 30 years.

BACKGROUND/AIMS: We investigated the body composition and nutritional status of extremely long-term (more than 30 years) hemodialysis patients. METHODS: Eighty outpatients receiving maintenance hemodialysis (including 18 for more than 30 years) were enrolled. We classified the patients according to the duration of hemodialysis therapy (less than 10 years, 10-20 years, 20-30 years, or over 30 years) and compared the laboratory and anthropometric data. RESULTS: No significant differences in age or the total protein, albumin, total cholesterol, triglyceride or CRP levels were observed. The corrected body mass index (BMI) was significantly lower in the more than 30 years than in the less than 10 years group. The corrected arm muscle area (AMA) was significantly lower in the more than 30 years group than in the other groups. CONCLUSION: In extremely long-term hemodialysis outpatients, the BMI and AMA were reduced, whereas nutritional markers were relatively preserved.

The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age.

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

Facility hemodialysis vascular access use and mortality in countries participating in DOPPS: an instrumental variable analysis.

BACKGROUND: Previously, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown large international variations in vascular access practice. Greater mortality risks have been seen for hemodialysis (HD) patients dialyzing with a catheter or graft versus a native arteriovenous fistula (AVF). To further understand the relationship between vascular access practice and outcomes, we have applied practice-based analyses (using an instrumental variable approach) to decrease the treatment-by-indication bias of prior patient-level analyses. STUDY DESIGN: A prospective observational study of HD practices. SETTING & PARTICIPANTS: Data collected from 1996 to 2004 from 28,196 HD patients from more than 300 dialysis units participating in the DOPPS in 12 countries. PREDICTOR OR FACTOR: Patient-level or case-mix-adjusted facility-level vascular access use. OUTCOMES/MEASUREMENTS: Mortality and hospitalization risks. RESULTS: After adjusting for demographics, comorbid conditions, and laboratory values, greater mortality risk was seen for patients using a catheter (relative risk, 1.32; 95% confidence interval, 1.22 to 1.42; P < 0.001) or graft (relative risk, 1.15; 95% confidence interval, 1.06 to 1.25; P < 0.001) versus an AVF. Every 20% greater case-mix-adjusted catheter use within a facility was associated with 20% greater mortality risk (versus facility AVF use, P < 0.001); and every 20% greater facility graft use was associated with 9% greater mortality risk (P < 0.001). Greater facility catheter and graft use were both associated with greater all-cause and infection-related hospitalization. Catheter and graft use were greater in the United States than in Japan and many European countries. More than half the 36% to 43% greater case-mix-adjusted mortality risk for HD patients in the United States versus the 5 European countries from the DOPPS I and II was attributable to differences in vascular access practice, even after adjusting for other HD practices. Vascular access practice differences accounted for nearly 30% of the greater US mortality compared with Japan. LIMITATIONS: Possible existence of unmeasured facility- and patient-level confounders that could impact the relationship of vascular access use with outcomes. CONCLUSIONS: Facility-based analyses diminish treatment-by-indication bias and suggest that less catheter and graft use improves patient survival.

Characteristics of dialysis-related amyloidosis in patients on haemodialysis therapy for more than 30 years.

BACKGROUND: Dialysis-related amyloidosis is one of the chronic the complications of haemodialysis. We conducted an investigation of dialysis-associated amyloidosis in extremely long-term survivors. METHODS: Twenty-one patients on haemodialysis for more than 30 years ('30+' group) and 13 patients on haemodialysis for 20-30 years ('20-30' group) at Sangenjaya Hospital were enrolled in this study. The frequencies of operations for conditions related to haemodialysis-related amyloidosis were examined. RESULTS: The mean age at the start of haemodialysis was younger in the '30+' group (29.1 +/- 7.3 years) than in the '20-30' group (40.5 +/- 8.2 years, P = 0.0003). Eighteen (85.7%) patients had undergone surgery for CTS, six (28.6%) had undergone surgery for trigger finger and six (28.6%) had undergone surgery for cervical destructive spondyloarthropathy (DSA) at 30 years after the start of haemodialysis therapy. Patients who were over the age of 30 years at the start of dialysis therapy more frequently underwent CTS operations (100%) than those who were under 30 years of age at the start of dialysis (76.9%; P = 0.025) in the '30+' group at 30 years after the start of haemodialysis. The frequencies of operations for CTS did not differ significantly between the '20-30' group and the '30+' group. CONCLUSIONS: Haemodialysis-associated amyloidosis was common in extremely long-term survivors. Even though the mean age at the start of haemodialysis was younger in the '30+' group than in the '20-30' group, the frequency of operations for CTS did not differ. This may be attributable to the recent advances in haemodialysis technologies.

The survival advantage for haemodialysis patients taking vitamin D is questioned: findings from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Retrospective studies of haemodialysis patients from large dialysis organizations in the United States have indicated that intravenous vitamin D may be associated with a survival benefit. However, patients prescribed vitamin D are generally healthier than those who are not, suggesting that treatment by indication may have biased previous findings. Additionally, no survival benefit associated with vitamin D has been shown in a recent meta-analysis in CKD patients. Because treatment-by-indication bias due to both measured and unmeasured confounders cannot be completely accounted for in standard regression or marginal structural models (MSMs), this study evaluates the association between vitamin D and mortality among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS) using standard regression and MSMs with an expanded set of covariates, as well as by instrumental variable models to minimize potential bias due to unmeasured confounders. METHODS: Data from 38 066 DOPPS participants from 12 countries between 1996 and 2007 were analysed. Mortality risk was assessed using standard baseline and time-varying Cox regression models, adjusted for demographics and detailed comorbidities, and MSMs. In models similar to instrumental variable analysis, the facility percentage of patients prescribed vitamin D, adjusted for the patient case mix, was used to predict patient-level mortality. RESULTS: Vitamin D prescription was significantly higher in the USA compared to other countries. On average, patients prescribed vitamin D had fewer comorbidities compared to those who were not. Vitamin D therapy was associated with lower mortality in adjusted time-varying standard regression models [relative ratio (RR) = 0.92 (95% confidence interval: 0.87-0.96)] and baseline MSMs [RR = 0.84 (0.78-0.98)] and time-varying MSMs [RR = 0.78 (0.73-0.84)]. No significant differences in mortality were observed in adjusted baseline standard regression models for patients with or without vitamin D prescription [RR = 0.98 (0.93-1.02)] or for patients in facility practices where vitamin D prescription was more frequent [RR for facilities in 75th versus 25th percentile of vitamin D prescription = 0.99 (0.94-1.04)]. CONCLUSIONS: Vitamin D was associated with a survival benefit in models prone to bias due to unmeasured confounding. In agreement with a meta-analysis of randomized controlled studies, no difference in mortality was observed in instrumental variable models that tend to be more independent of unmeasured confounding. These findings indicate that a randomized controlled trial of vitamin D and clinical outcomes in haemodialysis patients are needed and can be ethically conducted.

G protein subtype specificity of rhodopsin intermediates metarhodopsin Ib and metarhodopsin II.

Rhodopsin is one of the members of the G protein-coupled receptor family that can catalyze a GDP-GTP exchange reaction on the retinal G protein transducin (Gt) upon photon absorption. There are at least two intermediate states, meta-Ib and meta-II, which exhibit direct interaction with Gt. Meta-Ib binds to GDP-bound Gt, while meta-II forms a complex with Gt having no nucleotide, suggesting that meta-Ib is a state that initially interacts with Gt. Here we investigated whether or not meta-Ib exhibits specific interaction with G protein similar to meta-II, by examining the binding efficiencies of meta-Ib and meta-II to Gialpha and its mutants whose C-terminal 11 amino acids were replaced with those of Goalpha, Gqalpha and Gsalpha. The affinity of meta-Ib to the C-terminal 11 amino acids of Gtalpha was similar to those of Gialpha and its mutant with Goalpha's C-terminal 11 amino acids, whereas meta-II exhibited affinity to the C-terminal 11 amino acids of Gialpha mutant with Goalpha's C-terminal 11 amino acids about half of what was seen for Gtalpha and Gialpha. Both intermediates exhibited no affinity to the Gialpha mutants containing the C-terminal 11 amino acids of Gqalpha and Gsalpha. These results suggested that meta-Ib is the state that exhibits specific interaction with G protein as meta-II does, although meta-Ib exhibits a slightly lenient binding selectivity compared to that of meta-II.

Prevalence and determinants of hypertension in chronic hemodialysis patients in Japan.

Hypertension is common in chronic hemodialysis (HD) patients. However, its prevalence and determinants have not been studied in a large HD population. We analyzed the database of the Japanese Society for Dialysis Therapy (JSDT) registry, which conducts an annual survey of chronic dialysis patients throughout Japan. We compiled those who were on HD three-times per week and aged 20 years and over at the end of 2000 (JSDT standard analysis file 001). Hypertension was defined as predialysis systolic blood pressure (SBP) > or =140 mm Hg or predialysis diastolic blood pressure (DBP) > or =90 mm Hg. Adjusted odds ratios (95% confidence interval) for the determinants of hypertension were calculated by the multivariate logistic regression analysis. A total of 65 393 people (men, 60.2%; mean age +/- SD, 60.9 +/- 12.8 years; and mean duration of HD +/- SD, 95.3 +/- 74.0 months) were studied. Mean +/- SD levels of SBP and DBP were 154.9 +/- 23.8 mm Hg and 80.5 +/- 13.7 mm Hg before the HD session. Hypertension was noted in 77.5% of patients. Prescription of antihypertensive drugs and erythropoietin was made to 60.7% and 82.0% of patients, respectively. Both SBP and DBP were higher in those who were prescribed antihypertensive drugs (mean, 160.4/81.9 mm Hg), than those without drugs (mean, 146.9/78.5 mm Hg) (in both cases P < 0.0001). Hypertension was positively associated with men (adjusted odds ratio (OR), 1.258; 95% confidence interval (CI), 1.188-1.333; P < 0.0001), age (OR, 1.004; CI, 1.001-1.006; P < 0.01), duration of HD (OR, 0.769; CI, 0.728-0.812; P < 0.0001), serum albumin (OR, 1.369; CI, 1.286-1.458; P < 0.0001), and change in body weight by dialysis session (DeltaBW) (OR, 1.176; CI, 1.159-1.194; P < 0.0001), and was negatively associated with Kt/V (OR, 0.600; CI, 0.543-0.664; P < 0.0001), and hematocrit (OR, 0.964; CI, 0.959-0.970; P < 0.0001). The distribution of DeltaBW was normal in shape and in about 22% of patients the range was from 4.0% to 4.9%. There was a significant positive relationship between the prevalence of hypertension and DeltaBW (R(2) = 0.8549). The higher the DeltaBW, the more the prescription rate of antihypertensive drugs increased (R(2) = 0.9102). Results showed that the prevalence of hypertension was significantly associated with volume excess and serum levels of albumin, calcium, and phosphorous in chronic HD patients. Despite the high prescription rate of antihypertensive drugs, control of blood pressure remains unsatisfactory.

Achievement of the Japanese Society for Dialysis Therapy guideline targets for mineral metabolism measures: one Japanese university center result.

A consensus conference for the Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Dialysis Patients was conducted in the general meeting of the Japanese Society for Dialysis Therapy (JSDT) in June 2006, and the guidelines were proposed in the Journal of JSDT in 4 months later. The aim of this study was performed on the status of observance with the data, based on 6 months later proposal of the guidelines. Only 48.9% stayed within the range specified by the calcium and phosphorus guideline. Moreover, only 12% of patients were able to remain within the ranges specified by all three guidelines (calcium, phosphorus, and PTH), 6 months later proposal of the guidelines. In our institution, compliance with the JSDT guidelines was inadequate. Major reasons were the special characteristics of the medical care system and patients in our institution as a university hospital. Further improvement in the contents and method of the use of the guidelines is necessary alongside observation of the present situation in Japan.

Overview of regular dialysis treatment in Japan (as of 31 December 2005).

A statistical survey conducted at the end of 2005 covered 3985 medical facilities across Japan, and 3940 facilities (98.87%) responded. The dialysis population in Japan at the end of 2005 was 257,765, which showed an increase of 9599 patients (3.87%) from the end of the previous year. The number of patients per million was 2017.6. The crude death rate for one year (from the end of 2004 to the end of 2005) was 9.5%. The mean age of the patients who began dialysis (in 2005) was 66.2 years, and the mean age of the entire dialysis population was 63.9 years. The primary diseases of the patients who began dialysis were diabetic renal disease (42.0%) and chronic glomerulonephritis (27.3%). The mean (+/-SD) serum ferritin concentration of all the dialysis patients was 191 (+/-329) ng/mL. The percentages of antihypertensive agents administered to the hemodialysis patients were as follows: calcium-channel blocker, 50.3%; angiotensin-converting enzyme inhibitor, 11.5%; and angiotensin II-receptor blocker, 33.9%. Of the peritoneal dialysis patients, 33.4% used automated peritoneal dialysis devices. Moreover, 7.3% of the peritoneal dialysis patients received dialysis treatment only in the daytime, and 15% received the treatment only at night. Icodextrin solution was used by 37.2% of the peritoneal dialysis patients. The average amount of dialysis solution used by the peritoneal dialysis patients was 7.43 (+/-2.52) L/day and the average amount of removal fluid was 0.81 (+/-0.60) L/day. A peritoneal equilibration test was conducted on 67% of the patients, and the mean dialysate to plasma creatinine ratio was 0.65 (+/-0.13). The annual incidence of peritonitis in the peritoneal dialysis patients was 19.7%. Of the 126 040 patients who responded to the inquiry of the therapeutic situation of peritoneal dialysis, 676 (0.7%) had a history of encapsulated peritoneal sclerosis and 66 (0.1%) were treated for encapsulated peritoneal sclerosis. The mean life expectancy of the dialysis population in 2003 was calculated according to sex and age. Results showed that the mean life expectancy of the dialysis population was approximately 40-60% of that of the general population of the same sex and age.

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study.

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.

Prevalence of hepatitis E virus infection in regular hemodialysis patients.

The percentage of patients infected with blood-borne diseases, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, is high in patients undergoing hemodialysis regularly. Hepatitis E virus (HEV) is transmitted via the fecal-oral route, and blood-borne HEV infection has also been reported recently. On the basis of these findings, we investigated the actual status of HEV infection in regular hemodialysis patients. Out of 1077 patients undergoing hemodialysis at two key hospitals and three outpatient hemodialysis clinics, 300 were randomly selected as the subjects. Among these 300 hemodialysis patients, 19.0% were IgG-type anti-HEV antibody-positive. The percentage of HEV-infected patients increased with patient age and it was particularly high in patients 40 years of age or older. The percent IgG-type anti-HEV antibody positivity was not significantly different (P = 0.14) between anti-HCV antibody-positive patients (27.8%) and anti-HCV antibody-negative patients (17.8%). The percentage of HEV-infected patients among the hemodialysis patients was higher than that previously reported among patients with healthy kidneys. No correlation was observed between the percentage of HEV-infected patients and HCV infection incidence or a history of blood transfusion. The percent IgG-type anti-HEV antibody positivities were significantly different among the facilities. It was impossible to specify the route of infection, and the correlation between the incidence of infection and hemodialysis therapy was not clear. Because more routes of infection are possible for patients undergoing dialysis than for persons with normal kidney function, it seems necessary to analyze the significance of infection incidence, the route of infection and infection prevention measures.

An overview of regular dialysis treatment in Japan (as of 31 December 2004).

A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%.