Hidetomo Nakamoto

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 m2. 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 HCO3‐; 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.

Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study

BACKGROUND Pruritus in haemodialysis patients is an intractable disease and substantially impairs their quality of life. Based on the results of our earlier clinical study, we hypothesized that the micro-(mu) opioid system is itch-inducible, whereas the kappa (kappa) system is itch-suppressive. METHODS The efficacy and safety of nalfurafine hydrochloride (a novel kappa-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 microg of the drug or a placebo orally for 14 days using a double-blind design in 337 haemodialysis patients with itch that was resistant to currently available treatments, such as antihistamines. RESULTS The mean decrease in the visual analogue scale (VAS) from baseline, the studys primary endpoint, was significantly larger in the 5-microg nalfurafine hydrochloride group (n = 114) than in the placebo group (n = 111, P = 0.0002, one-sided test at 2.5% significance level). The decrease in the VAS in the 2.5-microg group (n = 112) was also significantly larger than that in the placebo group (P = 0.0001). The incidence of adverse drug reactions (ADRs) was 35.1% in the 5-microg group, 25.0% in the 2.5-microg group and 16.2% in the placebo group. Moderate to severe ADRs were observed in 10 of the 226 patients. The most common ADR was insomnia (sleep disturbance), seen in 24 of the 226 nalfurafine patients. CONCLUSIONS This Phase III, randomized, double-blind, placebo-controlled, parallel-group, prospective study based on VAS evaluations clearly showed that orally taken nalfurafine hydrochloride effectively reduced itches that were otherwise refractory to currently available treatments in maintenance haemodialysis patients, with few significant ADRs. This novel drug was officially approved for clinical use in January 2009 by the Ministry of Health, Labour and Welfare of Japan.

Newly Developed Immobilized Polymyxin B Fibers Improve the Survival of Patients with Sepsis

Background: Sepsis and septic shock are still major causes of morbidity and mortality in spite of the availability of powerful and broadly active antibiotics. Methods: A prospective, open and randomized trial of the effect of immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis throughout a follow-up period of 28 days or until discharge, if earlier, was carried out. Ninety-eight patients were included who met at least 4 of the criteria for systemic inflammatory response syndrome due to infection. The patients were classified into three groups based on their Acute Physiology and Chronic Health Evaluation (APACHE) II score. Results: The overall survival rate was significantly improved by using PMX-F compared to the control group (41 vs. 11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more severe sepsis with an APACHE II score of 20–29, PMX-F still maintained efficacy in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not improve the survival rate in patients with an APACHE II score of greater than 30 (survival rate 7 vs. 0%) (p = 0.59). Conclusion: From these results, it is concluded that treatment with PMX-F in patients with sepsis is effective and prolongs the survival rate when applied at an early stage of sepsis. However, in severe sepsis, this therapy does not improve the survival rate.

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.

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 38 055 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 30 710; a slight decrease from 2011 (30 743). The dialysis patient population has been growing every year in Japan; it was 310 007 at the end of 2012, which exceeded 310 000 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 16 000 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 21 725, a marked increase from that in 2011 (14 115). In particular, the number of patients who underwent on‐line HDF increased threefold from 4890 in 2011 to 14 069 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).

An overview of regular dialysis treatment in Japan (as of 31 December 2007).

A nationwide statistical survey of 4098 dialysis facilities was conducted at the end of 2007, and 4052 facilities (98.88%) participated. The number of patients undergoing dialysis at the end of 2007 was determined to be 275 242, an increase of 10 769 patients (4.1%) compared with that at the end of 2006.The number of dialysis patients per million at the end of 2007 was 2154. The crude death rate of dialysis patients at the end of 2007 from the end of 2006 was 9.4%. The mean age of new patients begun on dialysis was 66.8 years and the mean age of the entire dialysis patient population was 64.9 years. For the primary diseases of new patients begun on dialysis, the percentages of patients with diabetic nephropathy and chronic glomerulonephritis were 43.4% and 23.8%, respectively. The percentages of facilities that achieved the control standard of endotoxin concentration in the dialysate solution of <0.05 EU/mL and those that achieved a bacterial count of <100 cfu/mL in the dialysate solution, as specified by the Japanese Society for Dialysis Therapy, were 93.6% and 97.4%, respectively. The percentage of patients positive for the hepatitis C virus antibody among the entire dialysis population significantly decreased from 15.95% at the end of 1999 to 9.83% at the end of 2007. The mean hemoglobin concentration in all the dialysis patients at the end of 2007 was 10.27 (±1.32, SD) g/dL, which has scarcely changed over the last three years. The numbers of male and female patients with a history of hip fracture were 142.9 and 339.0 per 10 000 dialysis patients, respectively, showing an extremely high prevalence among female patients. A history of hip fracture correlates with a low body mass index, serum albumin concentration, and a history of diabetes. The serum creatinine level of patients upon introduction to dialysis was 8.34 (±3.55) mg/dL, and the estimated glomerular filtration rate was 5.43 (±3.43) mL/min/1.73 m2 for the patients who were newly begun on dialysis in 2007.

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.

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.

Efficacy and Safety of a Novel ĸ-Agonist for Managing Intractable Pruritus in Dialysis Patients

Background: Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year. Methods: This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch. Results: Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation. Conclusions: Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.

Overview of Regular Dialysis Treatment in Japan as of 31 December 2006

A statistical survey of dialysis patients for the year 2006 was carried out for 4051 medical facilities across Japan, and responses were received from 3985 (98.37%) facilities. There were 264 473 dialysis patients (including 9003 peritoneal dialysis patients) in Japan at the end of 2006, which showed an increase of 6708 (2.6%) from the end of 2005. The number of patients per million population was 2069.9. The crude mortality rate during 2006 was 9.2%. The mean age of the patients who began dialysis (in 2006) was 66.4 years, and the mean age of the entire dialysis population was 64.4 years. The primary renal diseases of the patients who began dialysis were diabetic nephropathy (42.9%), chronic glomerulonephritis (25.6%), and nephrosclerosis (9.4%). Of the 3488 facilities that participated in the survey on the dialysate water quality, 2873 facilities (82.4%) measured the endotoxin concentration in the dialysate; and 1197 facilities (37.1%) out of 3228 measured the bacterial count in the dialysate. The mean hemoglobin concentration in the dialysis population at the end of 2006 was 10.23 ± 1.33 g/dL, which was equal to that at the end of 2005 (10.23 ± 1.37 g/dL). The mean concentration of serum creatinine in 15 853 patients who started dialysis during 2006 was 8.37 ± 3.58 mg/dL. The estimated glomerular filtration rate, which was calculated with formula modified for the Japanese population from the Modification of Diet in Renal Disease (MDRD) Study equation, was 5.46 ± 6.60 mL/min/1.73 m2.