Non-A Blood Type Is a Risk Factor for Poor Cardio-Cerebrovascular Outcomes in Patients Undergoing Dialysis.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The primary endpoint was observed in 73 patients during a median follow-up period of 1182 days, including 16/149 (11%) with blood type A, 22/81 (27%) with blood type B, 26/99 (26%) with blood type O, and 9/36 (25%) with blood type AB. At baseline, no difference was found in the echocardiographic parameters. Multivariable Cox regression analyses revealed that blood type (type A vs. non-A type; hazard ratio (HR): 0.46, 95% confidence interval (95% CI): 0.26-0.81, p = 0.007), age (per 10-year increase; HR: 1.47, 95% CI: 1.18-1.84), antiplatelet or anticoagulation therapy (HR: 1.91, 95% CI: 1.07-3.41), LVEF (per 10% increase; HR: 0.78, 95% CI: 0.63-0.96), and LV mass index (per 10 g/m2 increase; HR: 1.07, 95% CI: 1.01-1.13) were the independent determinants of the primary endpoint. Kaplan-Meier curves also showed a higher incidence of the primary endpoint in the non-A type than type A (Log-rank p = 0.001). Dialysis patients with blood type A developed cardio-cerebrovascular events more frequently than non-A type patients.

Impact of left ventricular hypertrophy on clinical outcomes in patients with dialysis: a single-center study in Japan.

PURPOSE: Left ventricular hypertrophy (LVH) is a well-known risk factor for poor clinical outcomes in patients undergoing dialysis. However, little evidence supports the above notion in Japan, and the influence of subtypes of LVH on prognosis. METHODS: We investigated 367 patients undergoing dialysis who underwent routine echocardiographic examinations between April and September 2018. LVH was defined as any LV mass ≥ 115 g/m2 in men and ≥ 95 g/m2 in women obtained by echocardiography. The primary endpoint was a composite outcome including all-cause death, admission due to heart failure, and ischemic heart event or stroke. LVH was divided into subtype-groups according to eccentric hypertrophy or concentric hypertrophy, and with and without hypertension. RESULTS: LVH was observed in 171 (47%) patients. The primary endpoint was observed in 58 patients (16%) during the median follow-up period of 500 days. Multivariable Cox regression analyses identified four independent risk factors for the primary endpoint: age, pulse rate, serum albumin level, and LV mass index (per 10-g/m2 increase; hazard ratio: 1.12, 95% confidence interval: 1.06-1.18, P < 0.001). Kaplan-Meier analyses demonstrated that patients with LVH had a worse prognosis than those without LVH in terms of the primary endpoint (log-rank P < 0.001). The incidence of the primary outcome was not significantly different between patients with eccentric or concentric hypertrophy, and between LVH patients with and without hypertension. CONCLUSION: Japanese patients with LVH undergoing dialysis had a worse prognosis than those without LVH in terms of the composite clinical endpoint.

Impact of serum magnesium and bone mineral density on systemic fractures in chronic hemodialysis patients.

INTRODUCTION: Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) can be used to predict fractures, but its clinical utility has not been fully established in chronic kidney disease (CKD) patients. Magnesium is an essential trace element. Although magnesium is associated with the risk of fractures in non-CKD populations, the relationship is unknown in CKD patients. METHODS: BMD and serum magnesium levels were measured in 358 stable outpatients undergoing maintenance hemodialysis therapy. The primary outcome was fragility fracture. Patients were divided into groups according to the median level of magnesium and the normal threshold value of lumbar spine BMD. RESULTS: During the median follow-up period of 36 months, 36 (10.0%) fractures occurred. The cumulative incidence rates of fractures were 17.6% and 5.2% [adjusted hazard ratio (aHR) 2.31, 95% confidence interval (CI) 1.03-5.17, P = 0.030] in the lower (<2.6 mg/dL) and higher (≥2.6 mg/dL) magnesium (Mg) groups, respectively, and 21.2% and 7.3% (aHR 2.59, 95% CI 1.09-6.16, P = 0.027) in the low- and high-BMD groups, respectively. The lower-Mg and low-BMD group had a 9.21-fold higher risk of fractures (95% CI; 2.35-47.00; P = 0.0010) than the higher-Mg and high-BMD group. Furthermore, adding both magnesium levels and lumbar spine BMD levels to the established risk factors significantly improved the prediction of fractures (C-index: 0.784 to 0.830, p = 0.041). DISCUSSION/CONCLUSIONS: The combination of serum magnesium and lumbar spine BMD can be used for fracture risk stratification and synergistically improves the prediction of fractures in CKD patients.

Multicenter study of pegylated interferon α-2a monotherapy for hepatitis C virus-infected patients on hemodialysis: REACH study.

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)-infected dialysis patients. The rate of HCV-infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α-2a (PEG-IFNα-2a) monotherapy in HCV-infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 µg PEG-IFNα-2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 µg PEG-IFNα-2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG-IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Identification of hemodialysis patients' common problems using the International Classification of Functioning, Disability and Health.

The aim of this study was to identify the common health problems of Japanese patients on hemodialysis (HD) using the International Classification of Functioning, Disability and Health (ICF). The participants of this study had been on HD for at least five years when they were interviewed. The ICF checklist was used to initially interview 32 HD patients. Fifty-seven categories of the ICF Checklist were identified as impaired; another 35 ICF categories, chosen based on interviews and expert discussion, as well as 8 categories relevant to HD, were included in the final checklist. This final checklist was then used to interview 104 patients. Overall, 10 categories in "Body functions" and 3 categories in "Body structures" were reported as problems by more than 50% of patients. Two categories in "Activities and participation" and 4 categories in "Environmental factors" were reported as restricted or a barrier for more than 30% of patients. A higher percentage of patients who started HD before 50 years of age and had a longer duration of HD reported problems in "Body functions" and "Body structures", while more patients with a shorter duration of HD reported problems in relationships with their family. Japanese patients on maintenance HD have various physical and psychosocial problems. In addition, HD duration and the age when HD was started affect patients' reports of physical and psychosocial problems.

Information-sharing system for disaster recovery of dialysis therapy in Japan.

If a natural disaster or other event causes damage that makes dialysis therapy impossible, what steps should be taken? Many actions will be required, including disaster recovery activities in the affected area as well as the performance of dialysis at substitute dialysis facilities outside the affected area. The Japanese Association of Dialysis Physicians (JADP), in collaboration with the Japan Association for Clinical Engineering Technologists (JACET), operates an "information sharing system" that will be essential when carrying out post-disaster activities. This system consists of a website and mailing lists on the Internet, and it has been used in 11 disasters so far.The JADP is an organization of doctors engaged in dialysis therapy. This association conducts investigation and research, education, and crisis management for dialysis therapy. The JACET is an organization that aims to enhance scientific knowledge and skills and to improve capabilities. This association also pursues improvement of the reliability of medical care involving life support systems and other medical equipment.

The organization and financing of end-stage renal disease treatment in Japan.

End-stage renal disease (ESRD) affects 230,000 Japanese, with about 36,000 cases diagnosed each year. Recent increases in ESRD incidence are attributed mainly to increases in diabetes and a rapidly aging population. Renal transplantation is rare in Japan. In private dialysis clinics, the majority of treatment costs are paid as fixed fees per session and the rest are fee for service. Payments for hospital-based dialysis are either fee-for-service or diagnosis-related. Dialysis is widely available, but reimbursement rates have recently been reduced. Clinical outcomes of dialysis are better in Japan than in other countries, but this may change given recent ESRD cost containment policies.

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan.

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV and HEV infections was investigated serologically and molecularly among 128 consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who contracted acute hepatitis between 1989 and 2005 in a city hospital, and among 416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples collected since the start of hemodialysis or employment, respectively. Between 1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005, however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2 (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two medical staff members (1978 and 2003) in previous studies, none of the 191 hemodialysis patients who had been negative for anti-HAV at the start of hemodialysis contracted HAV infection during the observation period of 7.6 +/- 6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative for anti-HAV at the start of employment acquired hepatitis A during the observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection. Clinical or subclinical HEV infection has occurred rarely during the last three decades, while HAV infection has markedly decreased at least since 1996.

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%.

Serological and molecular studies on subclinical hepatitis E virus infection using periodic serum samples obtained from healthy individuals.

Subclinical hepatitis E virus (HEV) infection among healthy individuals was studied serologically and molecularly. Serum samples collected at screening between March and April 2004 (or just before retirement) from 266 medical staff members (35 males, 231 females) who had been working for 8.8 +/- 8.5 (mean +/- standard deviation, range, 0.3-35.1) years in a city hospital in Japan and serum samples that had been collected from these staff members at the start of employment were tested for IgA, IgM, and IgG antibodies to HEV (anti-HEV) by in-house enzyme-linked immunosorbent assays. Overall, six subjects (2.3%) tested positive for anti-HEV IgG at the screening; among them, four subjects (1.5%) had already been positive for anti-HEV IgG at the start of employment and two subjects (0.8%) seroconverted after initiation of employment. Periodic serum samples that had been collected from the two seroconverted subjects were tested for HEV antibodies and HEV RNA. The two subjects became positive for anti-HEV IgG in 1978 or 2003, respectively, with no discernible elevation in alanine aminotransferase (ALT) level, and continued to be seropositive up through the screening date. Although anti-HEV IgM was not detectable in the two subjects, one was infected transiently with Japan-indigenous HEV strain of genotype 3 and the other was positive transiently for anti-HEV IgA. The present study indicates that even an individual with subclinical HEV infection had evidence of transient viremia in the absence of ALT elevation and that anti-HEV IgA detection may be useful for serological diagnosis of recent subclinical HEV infection.

Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion.

To investigate the prevalence of hepatitis E virus (HEV) infection among patients on maintenance hemodialysis, serum samples collected in January 2003 from 416 patients who had been undergoing hemodialysis for 7.6 +/- 6.3 (mean +/- standard deviation) (range, 0.3-26.0) years in a dialysis unit in Japan and serum samples that had been collected from these patients at the start of hemodialysis were tested for IgG antibodies to HEV (anti-HEV IgG) by an "in-house" enzyme-linked immunosorbent assay (ELISA). Overall, 39 patients (9.4%) had anti-HEV IgG in January 2003, and included 35 patients (8.4%) who had already been positive for anti-HEV IgG at the start of hemodialysis and 4 patients (1%) who seroconverted after initiation of hemodialysis. Periodic serum samples that had been collected from the four seroconverted patients were tested for HEV antibodies and HEV RNA. The four patients became positive for anti-HEV IgG in 1979, 1980, 1988, or 2003, and continued to be seropositive until the end of the observation period. Although anti-HEV IgM was not detectable in the four patients, three were infected transiently with apparently Japanese indigenous HEV strains of genotype 3. The patient who contracted HEV infection in 1979 had been transfused with 2 U of blood 21 days before the transient viremia: one of the two stored pilot serum samples had detectable HEV RNA with 100% identity to that recovered from the patient. Our study provides evidence of transfusion-transmitted HEV infection in Japan in 1979, and that the prevalence of de novo HEV infection during hemodialysis was low (1.1% or 4/374).

An overview of regular dialysis treatment in Japan (as of 31 December 2001).

Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

BACKGROUND: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. METHODS: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. RESULTS: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. CONCLUSIONS: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.

Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L-DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.