Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II, randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be involved, we conducted a phase II, randomized, controlled study to evaluate nemolizumab (anti-IL-31 receptor A antibody) in Japanese hemodialysis patients with UP. METHODS: Patients were randomly assigned (1:1:1:1:1) to one of four double-blind groups (receiving a single subcutaneous injection of nemolizumab 0.125, 0.5, or 2.0 mg/kg, or placebo on Day 1) or an open-label reference group (receiving oral nalfurafine hydrochloride 2.5-5 µg once daily for 12 weeks). The primary endpoint was the difference in the absolute change in pruritus visual analog scale (VAS) at Week 4 between placebo and each nemolizumab group. RESULTS: The primary efficacy endpoint was not met. The mean change from baseline with all three nemolizumab doses at Week 1, and with 0.5 mg/kg at Week 4, was greater than with placebo. Least square mean differences (95% confidence intervals) in the absolute changes between the placebo arm and each nemolizumab arm were - 2.4 (- 19.7, 14.9) for 0.125 mg/kg, - 8.7 (- 26.6, 9.2) for 0.5 mg/kg, and 0.4 (- 17.0, 17.8) for 2.0 mg/kg. Secondary efficacy parameters including the Shiratori severity score and 5-D itch score failed to show between-group differences. Patients with higher serum IL-31 levels at screening tended to have greater pruritus VAS reductions following nemolizumab treatment. CONCLUSIONS: In this phase II study in patients with UP, the primary efficacy parameter was not met. Nemolizumab was generally well tolerated with no clinically significant safety concerns. CLINICAL TRIAL REGISTRATION: JAPIC: JapicCTI-152961, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152961 .

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial.

BACKGROUND: Intermittent infusion hemodiafiltration -(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient's circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for -I-HDF with those of conventional hemodialysis (HD). OBJECTIVE: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of -I-HDF with that of HD in Japan. METHOD: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for -I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. RESULTS: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α1-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the ß2-MG and α1-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. CONCLUSIONS: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

The Japanese Clinical Practice Guideline for acute kidney injury 2016.

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.

The Japanese clinical practice guideline for acute kidney injury 2016.

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention is necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.

Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study.

Recent studies have revealed unique biological characteristics of molecular hydrogen (H2) as an anti-inflammatory agent. We developed a novel haemodialysis (E-HD) system delivering an H2 (30-80 ppb)-enriched dialysis solution by water electrolysis, and conducted a non-randomized, non-blinded, prospective observational study exploring its clinical impact. Prevalent chronic HD patients were allocated to either the E-HD (n = 161) group or the conventional HD (C-HD: n = 148) group, and received the respective HD treatments during the study. The primary endpoint was a composite of all-cause mortality and development of non-lethal cardio-cerebrovascular events (cardiac disease, apoplexy, and leg amputation due to peripheral artery disease). During the 3.28-year mean observation period, there were no differences in dialysis parameters between the two groups; however, post-dialysis hypertension was ameliorated with significant reductions in antihypertensive agents in the E-HD patients. There were 91 events (50 in the C-HD group and 41 in the E-HD group). Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92]) after adjusting for confounding factors (age, cardiovascular disease history, serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patients.

Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation.

BACKGROUND AND AIM: It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. SUBJECTS AND METHOD: 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. RESULTS: In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. CONCLUSION: The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.

Differences in characteristics and outcomes between community- and hospital-acquired acute kidney injury: A systematic review and meta-analysis
.

INTRODUCTION: No comprehensive review has examined the difference between community-acquired (CA) and hospital-acquired (HA) acute kidney injury (AKI) in terms of patient characteristics, in-hospital mortality, and hospital stay length. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of observational studies, using MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Library from their inceptions to April 10, 2016. Observational studies that (1) were published in peer-reviewed journals; (2) compared CA-AKI with HA-AKI, irrespective of the AKI definition during the same period; and (3) investigated in-hospital mortality and length of hospital stay were studied. Differences in the patients' baseline characteristics were analyzed, and a meta-analysis was conducted to compare the in-hospital mortality and length of hospital stay. RESULTS: Eight eligible observational studies with 17,939 patients were included. The systematic review showed that patients with CA-AKI had a significantly higher rate of AKI stage 3 compared with those with HA-AKI. The meta-analysis revealed that patients with CA-AKI showed significantly lower in-hospital mortality (odds ratio (OR) = 2.79; Z = 8.22; 95% confidence interval (CI), 2.18 - 3.56; p < 0.001) and shorter length of hospital stay (OR = 2.55; Z = 5.81; 95% CI, 1.86 - 3.50; p < 0.001). Subanalyses of studies conducted in developing and developed countries showed that patients with CA-AKI had lower in-hospital mortality and shorter length of hospital stay. Jackknife sensitivity analyses confirmed the replicability of these findings (p < 0.001). CONCLUSIONS: The results indicate that significant differences exist in clinical phenotypes between CA- and HA-AKI, even when standardized diagnosis criteria are used.
.

End-stage renal disease in Japanese children: a nationwide survey during 2006-2011.

BACKGROUND: End-stage renal disease (ESRD) in children is considered a rare, but serious condition. Epidemiological and demographic information on pediatric ESRD patients around the world is important to better understand this disease and to improve patient care. The Japanese Society for Pediatric Nephrology (JSPN) reported epidemiological and demographic data in 1998. Since then, however, there has been no nationwide survey on Japanese children with ESRD. METHODS: The JSPN conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011. RESULTS: The average incidence of ESRD was 4.0 per million age-related population. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2 % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis. Initial treatment modalities in patients who commenced renal replacement therapy (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT mortality rate was 18.2 deaths per 1000 person-years of observation. CONCLUSION: The incidence of ESRD is lower in Japanese children than in children of other high-income countries. Since 1998, notably, there has been a marked increase in pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.

Peritoneal Dialysis Registry With 2012 Survey Report.

Since 2009, the peritoneal dialysis (PD) registry survey has been carried out as part of the annual nationwide survey conducted by the Statistical Survey Committee of the Japanese Society for Dialysis Therapy with the cooperation of the Japanese Society for Peritoneal Dialysis. In this report, the current status of PD patients is presented on the basis of the results of the survey conducted at the end of 2012. The subjects were PD patients who lived in Japan and participated in the 2012 survey. Descriptive analysis of various items was performed, which included the current status of the combined use of PD and another dialysis method such as hemodialysis (HD) or hemodiafiltration (HDF), the method of exchanging dialysate, the use of an automated peritoneal dialysis (APD) machine, and the rates of peritonitis and catheter exit-site infection. From the results of the facility survey in 2012, the number of PD patients was 9514, a decrease of 128 from 2011. Among the entire dialysis patient population, 3.1% were PD patients, a decrease of 0.1%. Among the studied patients, 347 had a peritoneal catheter and underwent peritoneal lavage, 175 were started on PD in 2012 but introduced to other blood purification methods in the same year, and 1932 underwent both PD and another dialysis method such as HD or HDF. The percentage of patients who underwent PD and another dialysis method increased with PD vintage: <1 year, 4.8%; 1 to <2 years, 9.2%; 2 to <4 years, 16.3%; 4 to <8 years, 32.0%; and ≥8 years, 47.5%. The percentage of PD patients who completely manually exchanged the dialysate was 29.8%. The percentages of PD patients who used a double-bag exchange system with ultraviolet-light irradiation and those who used the same system but with a sterile connecting device were 54.7 and 13.9%, respectively. The percentage of patients on PD for <1 year using an APD machine was 43.4%, and it decreased with a PD vintage of ≥2 years. The mean rate of peritonitis was 0.22 per patient per year. The mean rate of catheter exit-site infections was 0.36 per patient per year.

An overview of regular dialysis treatment in Japan (as of 31 December 2012).

A nationwide statistical survey of 4279 dialysis facilities was conducted at the end of 2012, among which 4238 responded (99.0%). The number of new dialysis patients was 38055 in 2012. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2012 was 30710; a slight decrease from 2011 (30743). The dialysis patient population has been growing every year in Japan; it was 310007 at the end of 2012, which exceeded 310000 for the first time. The number of dialysis patients per million at the end of 2012 was 2431.2. The crude death rate of dialysis patients in 2012 was 10.0%, a slight decrease from that in 2011 (10.2%). The mean age of new dialysis patients was 68.5 years and the mean age of the entire dialysis patient population was 66.9 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.2%). The actual number of new dialysis patients with diabetic nephropathy has been approximately 16000 for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.1%), followed by chronic glomerulonephritis (33.6%). The percentage of dialysis patients with diabetic nephropathy has been continuously increasing, whereas not only the percentage but also the actual number of dialysis patients with chronic glomerulonephritis has decreased. The number of patients who underwent hemodiafiltration (HDF) at the end of 2012 was 21725, a marked increase from that in 2011 (14115). In particular, the number of patients who underwent on-line HDF increased threefold from 4890 in 2011 to 14069 in 2012. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9514 and that of patients who did not undergo PD despite having a PD catheter in the abdominal cavity was 347. From the results of the patient survey, among the PD patients, 1932 also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) and HDF. The number of patients who underwent HD at home in 2012 was 393, a marked increase from that in 2011 (327).

Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients.

Elevated oxidative stress (OS) is associated with severe cardiovascular disease and premature death among patients treated with hemodialysis (HD). Oxidative stress is enhanced by contact between blood and dialysis membranes during HD sessions. This study aimed to clarify whether hydrogen (H2), which is a known antioxidant, is capable of suppressing increased OS induced during HD sessions. Eight patients on regular HD treatment were studied. Two HD sessions were performed in a cross-over design trial using standard and hydrogen-enriched solutions (mean of 50 p.p.b. H2; H2-HD). Blood samples were obtained from the inlet and outlet of the dialyzer during HD to determine changes in plasma levels of glutathione, hydrogen peroxide, and albumin redox state as a marker of OS. Comparison of inlet and outlet blood revealed significant decreases in total glutathione and reduced glutathione, as well as significant increases in hydrogen peroxide in both HD treatments. However, the mean proportion of reversibly oxidized albumin in outlet serum was significantly lower than that in inlet serum following the H2-HD session, whereas no significant changes were found in the standard solution session, suggesting that "intra-dialyzer" OS is reduced by H2 -HD. In conclusion, the application of H2-enriched solutions could ameliorate OS during HD.

Overview of regular dialysis treatment in Japan (as of 31 December 2011).

A nationwide statistical survey of 4255 dialysis facilities was conducted at the end of 2011. Responses were submitted by 4213 facilities (99.0%). The number of new patients started on dialysis was 38,613 in 2011. Although the number of new patients decreased in 2009 and 2010, it increased in 2011. The number of patients who died each year has been increasing; it was 30,743 in 2011, which exceeded 30,000 for the first time. The number of patients undergoing dialysis has also been increasing every year; it was 304,856 at the end of 2011, which exceeded 300,000 for the first time. The number of dialysis patients per million at the end of 2011 was 2385.4. The crude death rate of dialysis patients in 2011 was 10.2%, which exceeded 10% for the first time in the last 20 years. The mean age of new dialysis patients was 67.84 years and the mean age of the entire dialysis patient population was 66.55 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.3%). Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (36.7%), exceeding chronic glomerulonephritis (34.8%) which had been the highest until last year. The survey included questions related to the Great East Japan Earthquake, which occurred on 11 March 2011. The results on items associated with the Great East Japan Earthquake were reported separately from this report. The mean uric acid levels of the male and female patients were 7.30 and 7.19 mg/dL, respectively. Certain drugs for hyperuricemia were prescribed for approximately 17% of patients. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9642 and the number of patients who did not undergo PD despite having a peritoneal dialysis catheter was 369. A basic summary of the results on the survey items associated with PD is included in this report and the details were reported separately.

Darbepoetin alfa for the treatment of anemia in children undergoing peritoneal dialysis: a multicenter prospective study in Japan.

BACKGROUND: Darbepoetin alfa (DA) is an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia. Since DA has not been approved by the appropriate Japanese drug regulatory agencies for the indication of renal anemia in children in Japan, we have conducted a multicenter prospective study to determine the efficacy and safety of DA in Japanese children undergoing peritoneal dialysis (PD). METHODS: Pediatric patients subcutaneously receiving rHuEPO were switched to DA treatment for a period of 28 weeks. The conversion to the initial dose of DA was calculated as 1 µg DA for 200 IU rHuEPO, and DA was administered intravenously once every 2 weeks. The target hemoglobin (Hb) concentration was defined as 11.0 to ≤13.0 g/dL. In some patients, the dose of DA was adjusted appropriately to achieve this target level, and/or the dosing frequency changed to once every 4 weeks. RESULTS: In the 25 patients switched from rHuEPO to DA the mean Hb concentration increased from 9.9 ± 1.0 to 11.1 ± 1.0 g/dL at 8 weeks following commencement of the DA treatment. The target Hb concentration was achieved in 88 % of these patients, and 60 % maintained this target value on completion of the study. The dosing frequency was extended to once every 4 weeks in 60 % of patients. Twenty-four adverse events were noted in 11 of 25 patients (44 %); however, there was no causality between DA and adverse events. CONCLUSIONS: The results of this study suggest that intravenous administration of DA once every 2 or 4 weeks is an effective and safe treatment for renal anemia in Japanese children undergoing PD.

An overview of regular dialysis treatment in Japan (as of 31 December 2010).

A nationwide statistical survey of 4226 dialysis facilities was conducted at the end of 2010, and 4166 facilities (98.6%) responded. The number of new patients introduced into dialysis was 37,512 in 2010. This number has decreased for two consecutive years since it peaked in 2008. The number of patients who died in 2010 was 28,882, which has been increasing every year. The number of patients undergoing dialysis at the end of 2010 was 298,252, which is an increase of 7591 (2.6%) compared with that at the end of 2009. The number of dialysis patients per million at the end of 2010 was 2329.1. The crude death rate of dialysis patients in 2010 was 9.8%, and has been gradually increasing. The mean age of the new patients introduced into dialysis was 67.8 years and the mean age of the entire dialysis patient population was 66.2 years. Regarding the primary disease of the new patients introduced into dialysis, the percentage of patients with diabetic nephropathy was 43.6%, which is a slight decrease from that in the previous year (44.5%). Patients with diabetic nephropathy as the primary disease accounted for 35.9% of the entire dialysis patient population, which approaches the percentage of patients with chronic glomerulonephritis as the primary disease (36.2%). The percentage of patients who had undergone carpal tunnel release surgery (CTx) was 4.3%, which is a slight decrease from that at the end of 1999 (5.5%). The decrease in the percentage of patients who had undergone CTx was significant among the patients with dialysis durations of 20-24 years (1999, 48.0%; 2010, 23.2%). A total weekly Kt/V attributable to peritoneal dialysis and their residual functional kidney was 1.7 or higher for 59.4% of patients who underwent peritoneal dialysis.

Overview of regular dialysis treatment in Japan (as of 31 December 2009).

A nationwide statistical survey of 4196 dialysis facilities was conducted at the end of 2009, and 4133 facilities (98.5%) responded. The number of patients undergoing dialysis at the end of 2009 was determined to be 290 661, an increase of 7240 patients (2.6%) compared with that of 2008. The number of dialysis patients per million at the end of 2009 was 2279.5. The crude death rate of dialysis patients from the end of 2008 to the end of 2009 was 9.6%. The mean age of the new patients introduced into dialysis was 67.3 years old and the mean age of the entire dialysis patient population was 65.8 years old. Primary diseases such as diabetic nephropathy and chronic glomerulonephritis for new dialysis patients, showed a percentage of 44.5% and 21.9%, respectively. Based on the facilities surveyed, 84.2% of the facilities that responded to the questionnaire satisfied the microbiological quality standard for dialysis fluids for the Japanese Society for Dialysis Therapy (JSDT), with an endotoxin concentration of less than 0.05 EU/mL in the dialysis fluid. Similarly, 98.2% of the facilities surveyed satisfied another standard of the society of a bacterial count of less than 100 cfu/mL in the dialysis fluid. The facility survey indicated that the number of patients who were treated by blood purification by both peritoneal dialysis and extracorporeal circulation, such as hemodialysis, was 1720. Among the total number of patients, 24.8% were satisfied with the management target recommended in the treatment guidelines for secondary hyperparathyroidism. These standards are set by the JSDT, based on the three parameters, i.e. serum calcium concentration, serum phosphorus concentration, and serum intact parathyroid hormone concentration. According to the questionnaire, 9.8% of the patients were considered to have a complication of dementia.

Overview of regular dialysis treatment in Japan (as of 31 December 2008).

A nationwide statistical survey of 4124 dialysis facilities was conducted at the end of 2008 and 4081 facilities (99.0%) responded. The number of patients undergoing dialysis at the end of 2008 was determined to be 283,421, an increase of 8179 patients (3.0%) compared with that at the end of 2007. The number of dialysis patients per million at the end of 2008 was 2220. The crude death rate of dialysis patients from the end of 2007 to the end of 2008 was 9.8%. The mean age of the new patients begun on dialysis was 67.2 years and the mean age of the entire dialysis patient population was 65.3 years. For the primary diseases of the new patients begun on dialysis, the percentages of patients with diabetic nephropathy and chronic glomerulonephritis were 43.3% and 22.8%, respectively. Among the facilities that measured bacterial count in the dialysate solution in 2008, 52.0% of facilities ensured that a minimum dialysate solution volume of 10 mL was sampled. Among the patients treated by facility dialysis, 95.4% of patients were treated three times a week, and the average time required for one treatment was 3.92 ± 0.53 (SD) h. The average amounts of blood flow and dialysate solution flow were 197 ± 31 and 487 ± 33 mL/min, respectively. The number of patients using a polysulfone membrane dialyzer was the largest (50.7%) and the average membrane area was 1.63 ± 0.35 m(2). According to the classification of dialyzers by function, the number of patients using a type IV dialyzer was the largest (80.3%). The average concentrations of each electrolyte before treatment in patients treated with blood purification by extracorporeal circulation were 138.8 ± 3.3 mEq/L for serum sodium, 4.96 ± 0.81 mEq/L for serum potassium, 102.1 ± 3.1 mEq/L for serum chloride, and 20.7 ± 3.0 mEq/L for HCO(3) (-) ; the average serum pH was 7.35 ± 0.05. Regarding the type of vascular access in patients treated by facility dialysis, in 89.7% of patients an arteriovenous fistula was used and in 7.1% an arteriovenous graft was used. The percentage of hepatitis C virus (HCV)-positive patients who were HCV-negative in 2007 was 1.04%; the percentage is particularly high in patients with a period of dialysis of 20 years or longer. The risk of becoming HCV-positive was high in patients with low serum creatinine, serum albumin, and serum total cholesterol levels, and/or a low body mass index before beginning dialysis.