Norio Hanafusa

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.

An Overview of Regular Dialysis Treatment in Japan (As of 31 December 2013)

A nationwide survey of 4325 dialysis facilities was conducted at the end of 2013, among which 4268 (98.7%) responded. The number of new dialysis patients was 38 095 in 2013. 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 2013 was 30 751. The dialysis patient population has been growing every year in Japan; it was 314 438 at the end of 2013. The number of dialysis patients per million at the end of 2013 was 2470. The crude death rate of dialysis patients in 2013 was 9.8%. The mean age of new dialysis patients was 68.7 years and the mean age of the entire dialysis patient population was 67.2 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (43.8%). The actual number of new dialysis patients with diabetic nephropathy has almost been unchanged for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.6%), followed by chronic glomerulonephritis (32.4%). The percentage of dialysis patients with diabetic nephropathy has been increasing continuously, whereas the percentage of dialysis patients with chronic glomerulonephritis has been decreasing. The number of patients who underwent hemodiafiltration (HDF) at the end of 2013 was 31 371, a marked increase from that in 2012. This number is more than twice that at the end of 2011 and approximately 1.5 times the number at the end of 2012. In particular, the number of patients who underwent online HDF increased approximately fivefold over the last 2 years. Among 151 426 dialysis patients with primary causes of renal failure other than diabetic nephropathy, 10.8% had a history of diabetes. Among those with a history of diabetes, 26.8% used glycoalbumin as an indicator of blood glucose level; and 33.0 and 27.6% were administered insulin and dipeptidyl peptidase (DPP)–4 inhibitor, respectively, as a medication of diabetes. The facility survey showed that 9392 patients underwent peritoneal dialysis (PD). The patient survey revealed that 1920 of these PD patients also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) or HDF. The number of patients who underwent HD at home at the end of 2013 was 461, a marked increase from that at the end of 2012 (393).

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.

Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF1-mediated upregulation of Bax.

Chronic hypoxia is a major contributor to tubulointerstitial injury in various renal diseases and apoptosis is apparently involved. Although many studies report hypoxia-induced apoptosis in cultured tubular cells, information has been limited in proximal tubular cells, those from the most susceptible portion of renal tubules against hypoxia. This study was to confirm a role for apoptosis in hypoxic proximal tubular cells and to investigate its association with HIF-1. Temperature-sensitive SV40-immortalized rat proximal tubular cells (IRPTCs) showed apoptosis in 21.9+/-2.9% by hypoxia (0.2% O(2), 48h), with alterations in mitochondrial signaling such as Bcl2 and caspase-9. Bax mRNA was unaffected during the process. However, treating IRPTCs at the nonpermissive temperature showed an upregulation of Bax by hypoxia, which was abrogated by overexpressing dominant-negative HIF-1alpha. These findings extend previous reports on hypoxia-mediated tubular cell apoptosis and demonstrate the possible involvement of HIF-1 as an upstream molecule of Bax.

Japanese society for dialysis therapy renal data registry—a window through which we can view the details of Japanese dialysis population

The Japanese Society for Dialysis Therapy (JSDT) collects the clinical data from all the facilities to create a nation-wide registry system named JSDT Renal Data Registry (JRDR). This survey was begun in 1966 as a form of facility survey. Patient survey started in 1983. More than 95% of facilities respond to the survey on the basis of voluntary work of facility staffs. Therefore, JRDR has the longest history and the most comprehensive coverage. As for the prevalent patients, 304,856 patients are treated by dialysis therapy in Japan as of the year 2011. The demographics of the Japanese dialysis population have been markedly changing in terms of age, primary diagnoses and dialysis vintage. The mean age of prevalent population reaches 66.55 years at the end of 2011. The increase in the numbers of dialysis population is due to the growth of those older than 65 years old. Patients with the vintage longer than 20 years account for 8% of the entire population. Around 38 thousands patients started their dialysis treatments, whereas 31 thousands deceased. The disease burden of cardiovascular diseases as well as infection is substantial due to the demographic changes. Many evidences have been reported from the data obtained from JRDR to date. These findings covers a wide range of dialysis practice and are utilized for the development of JSDT guidelines. Therefore, JRDR has provided indispensable and fundamental data of Japanese dialysis population.

Theoretical basis of pathogenic substance removal during plasmapheresis.

This article explains theoretical considerations of prescribing plasmapheresis. It is important to consider several factors in prescribing apheresis: (i) the properties of pathogenic substances, such as molecular weight, distribution volume, compartment, and production rate; (ii) therapeutic conditions such as the processed plasma volume and the frequency of processing; and (iii) the patients condition, such as active bleeding or infection. A substances molecular weight determines whether it can be removed using a particular membrane filter. Substances with a small distribution volume and low production rate are removed. Consequently, the processed volume per total plasma volume is related to the single‐session efficacy. Nevertheless, even frequent therapy cannot reduce the total pool of a substance within the body if movement from outside the vessels is slow. Active bleeding or infection might be exacerbated by modalities other than simple plasma exchange with fresh plasma supplementation because such therapies cannot replenish substances other than albumin.