Yoshiharu Tsubakihara

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.

Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure

The optimal target hematocrit (Ht) level in recombinant human erythropoietin (rHuEPO) therapy remains controversial and has hardly been investigated in predialysis patients. We prospectively studied the regression of left ventricular hypertrophy (LVH) on echocardiography in nine predialysis patients with chronic renal failure after a partial correction (target Ht, 30%) and normalization (target Ht, 40%) of the Ht with rHuEPO treatment. Twenty-four-hour ambulatory blood pressure monitoring was also performed. The administration of rHuEPO significantly increased Ht to the target values. The rate of renal failure progression did not change during rHuEPO treatment for 12 months (Cr, from 6.2 +/- 2.0 to 5.5 +/- 2.1 mg/dL). The left ventricular mass index (LVMI) tended to decrease after a partial correction of anemia (Ht, 32.1% +/- 1.8%) at 4 months, whereas it tended to significantly decrease after normalization of Ht (Ht, 39.1% +/- 2.4%) at 12 months (baseline, 140.6 +/- 12.1 g/m2; partial correction, 126.9 +/- 10.0 g/m2; normalization, 111.2 +/- 8.3 g/m2). All patients had received antihypertensive medication before rHuEPO administration, and additional drugs were also required in four cases during the study. As a result, a good overall blood pressure control was obtained without any adverse effects on the circadian blood pressure rhythm. In conclusion, from the perspective of LVH regression, the normalization of Ht was found to be more effective than that associated with a partial correction of anemia during rHuEPO therapy.

2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease.

The Japanese Society for Dialysis Therapy (JSDT) guideline committee, chaired by Dr Y. Tsubakihara, presents the Japanese guidelines entitled “Guidelines for Renal Anemia in Chronic Kidney Disease.” These guidelines replace the “2004 JSDT Guidelines for Renal Anemia in Chronic Hemodialysis Patients,” and contain new, additional guidelines for peritoneal dialysis (PD), non‐dialysis (ND), and pediatric chronic kidney disease (CKD) patients.

Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder

Masafumi Fukagawa, Keitaro Yokoyama, Fumihiko Koiwa, Masatomo Taniguchi, Tetsuo Shoji, Junichiro James Kazama, Hirotaka Komaba, Ryoichi Ando, Takatoshi Kakuta, Hideki Fujii, Msasaaki Nakayama, Yugo Shibagaki, Seiji Fukumoto, Naohiko Fujii, Motoshi Hattori, Akira Ashida, Kunitoshi Iseki, Takashi Shigematsu, Yusuke Tsukamoto, Yoshiharu Tsubakihara, Tadashi Tomo, Hideki Hirakata, and Tadao Akizawa for CKD-MBD Guideline Working Group, Japanese Society for Dialysis Therapy

Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy

Diffuse proliferative immunoglobulin A (IgA) nephropathy has the potential risk for end-stage renal disease. However, treatment of IgA nephropathy has not been well established. To determine whether early treatment with corticosteroids ameliorates the proliferative lesions of diffuse proliferative IgA nephropathy, we conducted a prospective, randomized, controlled trial. Inclusion criteria were as follows: duration of abnormal urinalysis results less than 36 months, proteinuria less than 1.5 g/d of protein, serum creatinine level less than 1.5 mg/dL, and mesangial cell proliferation or matrix accumulation involving more than 50% of glomeruli. Twenty-one patients were randomly assigned to two groups: the corticosteroid group and the antiplatelet group. After 1 year of treatment, repeated renal biopsy was performed in 19 patients. We evaluated glomerular filtration rate, blood pressure, proteinuria, and histological parameters, including light microscopic findings and staining of alpha-smooth muscle actin (alphaSMA), as a marker of myofibroblast-like cells and fibronectin EDA (EDA-FN) as an indicator of renal fibrosis. After 1 year of treatment, proteinuria significantly decreased in the corticosteroid group. Histological findings, such as mesangial cell proliferation, mesangial matrix accumulation, and cellular crescents, showed significant improvement in the corticosteroid group but not in the antiplatelet group. Expression of alphaSMA in glomeruli significantly decreased in the corticosteroid group but not in the antiplatelet group. EDA-FN did not change in either group. We conclude that early treatment with corticosteroids for adult diffuse proliferative IgA nephropathy is effective in reducing renal injury.

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.

Effect of Renin-Angiotensin-Aldosterone System Triple Blockade on Non-Diabetic Renal Disease: Addition of an Aldosterone Blocker, Spironolactone, to Combination Treatment with an Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker

Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p<0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p<0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade. (Hypertens Res 2008; 31: 59−67)

High Prevalence of Obstructive Sleep Apnea and Its Association with Renal Function among Nondialysis Chronic Kidney Disease Patients in Japan: A Cross-Sectional Study

BACKGROUND AND OBJECTIVES Obstructive sleep apnea (OSA) affects one of five adults in the general population. Although a high prevalence of OSA has been reported among dialysis patients, the association between nondialysis chronic kidney disease (CKD) and OSA has not been fully investigated. This cross-sectional study aimed to investigate the prevalence of OSA among nondialysis CKD patients in Japan and the association between renal function and OSA. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Consecutive nondialysis CKD patients hospitalized mainly for CKD educational program, regardless of their sleep complaints, were enrolled. The diagnosis of OSA and its severity were measured using a type 3 portable monitor. RESULTS Overall (n=100, 68.0% male, median age 66.5 years, body mass index [BMI] 23.1 kg/m(2), estimated GFR [eGFR] 28.5 ml/min per 1.73 m(2)), 65% were diagnosed as OSA: mild OSA (apnea-hypopnea index [AHI] 5.0 to 14.9) in 32%, moderate OSA (AHI 15.0 to 29.9) in 25%, and severe OSA (AHI ≥ 30.0) in 8%. Multivariate logistic regression analysis revealed that a 10-ml/min per 1.73 m(2) decrease in eGFR was associated with a 42% increased odds of OSA after adjustment for age, BMI, and diabetes mellitus. Moreover, in a generalized linear model, eGFR was inversely correlated with AHI after adjustment for covariates. CONCLUSIONS This study demonstrated a high prevalence of OSA among nondialysis CKD patients in Japan and that the increased risk of OSA was significantly associated with decreased GFR among these patients. Further investigations are warranted to determine OSAs direct influence on cardiovascular disease.