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Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of β2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients.

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.

We examined the incidence rates of psychiatric disorders in end-stage renal failure patients on hemodialysis (HD) based on 4-year long-term follow-up. Among various psychiatric disorders, the frequency of three psychiatric disorders, dementia, delirium, and major depression, was relatively high. One-year incidence rate of whole psychiatric disorders was 10.6% (7.1% in non-aged and 13.7% in aged). One-year incidence rate of dementia in aged patients was 4.2% (dementia of the Alzheimer’s disease, 0.5%; multi-infarct dementia, 3.7%). One-year incidence rate of multi-infarct dementia in aged HD patients was 7.4 times as large as that in the elderly general populations, suggesting that aged HD patients tend to exhibit multi-infarct dementia. The high incidence rate may be closely related to advanced arteriosclerosis and other medical conditions. Psychiatric management is required for ESRD patients with three major psychiatric disorders, dementia, delirium, and major depression, in particular for aged patients with multi-infarct dementia who has received long-term HD therapy.

Background: The introduction of erythropoietinn stimulating agent (ESA) in clinical practice has completely altered the management of patients with chronic kidney disease. However, the successful correction of anemia has not always resulted in improvement of mortality in CKD patients. One of the main reasons for failure of preservation of renal function is excessive elevation of hemoglobin (Hb) levels for CKD patients. This indicates the need for maintaining appropriate target levels of Hb to preclude the progression of CKD. The aim of this study was to compare the effects of two Hb levels on progression of CKD patients in a 2 year period. Subjects: A total of 167 patients with chronic kidney disease (2mg

A statistical survey at the end of 1999 by the Japanese Society for Dialysis Therapy resulted in responses from 3, 220 (99.66%) of 3, 231 institutions providing dialysis. The survey found 197, 213 chronic dialysis patients in Japan, an increase of 6.4% (11, 891 patients) from the 1998 survey. The 1999 survey found a slight decrease in the gross annual mortality percentage compared to 1998 (9.7%). The mean age of patients newly introduced to dialysis increased to 63.4±13.9 (±SD) years in 1999. The mean age of the dialysis population at the end of 1999 was 60.6±13.3 years. The primary diseases leading to dialysis were diabetic nephropathy (36.2%) and chronic glomerulonephritis (33.6%).New survey items for 1999 survey included the following: 1) with/without reverse osmosis, 2) with/without dialysate endotoxin measurement and endotoxin concentration, 3) itchiness, 4) HBs and HBe antigen/antibody, 5) earlier hepatitis B vaccine inoculation, 6) HCV antibody/HCV-RNA, 7) serum glutamic pyruvic acid transaminase (GPT) activity, 8) hepatocellular carcinoma or cirrhosis, 9) previous limb amputation, 10) history of cerebral infarction, cerebral hemorrhage, or myocardial infarction, 11) loss of eyesight due to diabetic retinopathy or retinal circulatory disturbance, 12) serum cholesterol level, 13) number of cigarettes smoked, 14) platelet and leukocyte counts, 15) C-reactive protein levels, 16) height and body mass index (BMI), 17) tuberculosis within the previous year and 18) both the fluid substitution method in hemodiafiltration and the amount of substitution fluid.The survey findings for 1999 included 1) 93.0% of the patients were dialyzed using reverse osmosis 2) endotoxin concentrations tended to be lower in institutions with more patients, and 3) 56.7% of the patients experienced no itchiness and received no treatment for itchiness. Other survey findings were that 84.7% of the patients were HBs antigen (-) antibody (-), 1.9% were HBs antigen (+) antibody (-), and 13.0% were HBs antigen (-) antibody (+). The survey also found that 2.3% of patients were inoculated with Hepatitis B vaccine, 16.1% were HCV antibody (+), and 8.2% were HCV-RNA (+). The survey found that 2.1% of the patients had cirrhotic complications and 0.6% had hepatocellular carcinoma. The mean serum total cholesterol level was 162.84mg/dl, and the mean BMI was 20.61kg/m2. Using the Cox's proportional hazards model, a Kt/V of 1.4, a normalized protein catabolic rate of less than 0.9g/kg/day or more than 1.5g/kg/day, and a low creatinine generation rate were risk factors in the 6-year mid-term prognosis for hemodialysis patients.

A statistical survey of 3932 nationwide hemodi- alysis (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 neces- sarily 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 arte- rial blood HCO 3- . Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally max- acalcitol. 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 par- athyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D pre- paration 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%. Key Words: Calcium carbon- ate, Death rate, Intact parathyroid hormone, Sevelamer hydrochloride.

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with 3H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of 3H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.

To clarify the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 hemodialysis patients with renal anemia. Anemia improved significantly 12 weeks after r-HuEPO therapy (stage II) compared to pretreatment (stage I) and 6 weeks discontinuation (stage III) periods. Platelet count did not change among the three stages, however, mean platelet volume increased significantly at stage II in comparison with stage I. Ivy bleeding time (BT) significantly shortened at stage II and prolonged again at stage III. Although there were no significant changes in platelet aggregation, plasma TxB2, 6-keto-PGF1 alpha, F.VIII:C and F.VIII:Ag levels throughout the study, platelet adhesion and von Willebrand factor (vWf):Ag significantly increased at stages II and III. Augmentations in these parameters were more remarkable in BT-shortened patients (n = 12) than in the BT-unchanged group. These results indicate that correction of anemia with r-HuEPO brought about improvement in uremic hemostatic defect via the increase in red cell volume and vWf:Ag, and new production of platelets, reflected by the improvement in platelet adhesion.

A case of bilateral cortical necrosis (BCN) was reported because of her abnormal platelet count and aggregability. She was 26 years old primipara.In her past history, at the age of 11, she was operated because of papillary adenocarcinoma of the thyroid gland, when no abnormal bleeding was reported.After cesarean section, atonic hemorrhage occurred and anuria developed. Because BCN was suspected heparin and urokinase therapy were started (later, patchy BCN was verified by renal biopsy). Uremia was controlled by hemodialysis (3/week). Platelet count (Plt.) increased gradually to normal level within a week. After heparin cessation, Plt. continued to increase and exceeded 60×104/mm3. In spite of thrombocytosis, bleeding time (BT) was prolonged to more than 15 min. On 31st hospital day when Plt. was 40×104/mm3and BT more than 15 min., platelet aggregability was investigated by screen filtration pressure (SFP) method (normal range: 264.9±14.3mmHg when induced by 3μM ADP). Her aggregability was no more than 20mmHg. On 34th hospital day, she was attacked by generalized convulsion and tracheotomy was done. Despite 17 units of blood transfusion bleeding was not discontinued. Therfore, 6 units of packed platelet were transfused and bleeding was dramatically stopped within 2 hours. After this episode, BT was normalized while thrombocytosis persisted. On 59th hospital day when Plt. showed 48.1×104/mm3 and BT was 3.5min., platelet aggregability was investigated by SEP method and optical density (O. D.) method. Using SFP method 3μM ADP induced aggregability was 400mmHg. By O. D. method, 10μM ADP induced maximum aggregability (ADP max) was 32.8% (normal 70.2±2.6), 1μg/ml adrenaline induced maximum aggregability (adrenaline max) 90.8% (normal 40.6±4.0), and 1mg/ml collagen induded maximum aggregability (collagen max) 69.6% (normal 74.8±5.6), respectively.She discharged on 14th hospital day, when her creatinine clearance was 17L/day, BUN 31mg/dl, and creatinine 3.3mg/dl, and conservative management was indicated. On 178 th day after BCN, when Plt. revealed 27.6×104/mm3 and was 3min., platelet aggregability was investigated again. Using SFP method, 3μM ADP induced aggregability was 390mmHg, while by O. D. method, ADP max was 63.2%, adrenalin max 98.5%, and collagen max 82.4%, respectively.Throughout her clinical course, fibrin degradation products were 40μg/ml or less, fibrinogen 370-900mg/dl, and euglobulin lysis time 24 hours or more. CB-PC and cephalothin, which were administered when platelet aggregability decreased, were investigated in vitro by O. D. method, with no effect to platelet aggregability being found.

The southwestern region of Japan is known as a very high endemic area of human T-cell lymphotropic virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL) and probable causative agent for tropical spastic paraparesis and its Japanese version, HTLV-1-associated myelopathy (HAM). Hemodialysis (HD) patients seem to be at high risk for HTLV-1 infection even in other regions of Japan because they sometimes receive multiple blood transfusions. We examined antibody against ATL-associated antigen (ATLA-Ab) in 1,132 HD patients, including 1,066 patients in nonendemic areas (Chubu and Tokyo) and 66 in a highly endemic area (Okinawa). The HD patients in Okinawa showed the highest prevalence, 21.2% (14/66), while those in the Chubu area showed the lowest, 1.1% (10/846), and those in the Tokyo area an intermediate value, 2.7% (6/220). The prevalence of HD patients in each area was significantly higher than that of local blood donors, reflecting an increased prevalence roughly corresponding to the respective endemic rate. The average prevalence of ATLA-Ab among the HD patients was 2.7% (30/1,132), which was similar to that of HBs antigen (3.2%). In the nonendemic areas, 15 of 16 patients with ATLA-Ab had a history of blood transfusions, showing a significant correlation to the presence of ATLA-Ab (P less than 0.01), although four had family histories related to the endemic area. The relative risk of the presence of ATLA-Ab for HD patients with a history of blood transfusions was calculated as 10.3. In the endemic area of Okinawa, the relationship to blood transfusion was not so close, probably masked by the high background prevalence.

Why has the gross mortality of dialysis patients increased in Japan? Background The gross mortality of Japanese chronic dialysis patients gradually increased from 8.1% in 1983 to 9.4% in 1997. We describe the demographic changes in dialysis patients and clarify why the gross mortality has increased. Methods Data used in our analysis were taken from annual reports by the Patient Registration Committee of the Japanese Society for Dialysis Therapy. The relative risk of death was calculated by a logistic regression procedure and Cox proportional hazard model. Results The first-year survival starting from the initiation of dialysis therapy slowly improved from 0.836 in 1983 to 0.857 in 1996, but 5-year and 10-year survival consistently decreased in the same patient groups. The patients' mean age of beginning dialysis steadily increased from 51.9 in 1983 to 62.2 in 1997. The incidence of patients with diabetes as the original disease showed a tremendous increase from 15.6% in 1983 to 33.9% in 1997, and patients with nephrosclerosis also showed a twofold increase in our population. Heart failure accounted for 30–35% of mortality until 1991, but this started to decrease after 1992, when recombinant human erythropoietin became clinically available, and the level fell to 23.9% by 1997. The relative risk of death in the first year of initiating dialysis therapy decreased to almost half of the reference year 1983 ( P Conclusion The increase in the gross mortality of Japanese dialysis patients might not be due to a deteriorating quality of dialysis therapy, but rather is a reflection of accepting patients with older age and comorbid factors contributing to higher risks of mortality with dialysis therapy.

Several lines of evidence suggest that beta 2-microglobulin (beta 2M) accumulation in long-term hemodialysis (HD) patients results in so-called dialysis-associated amyloidosis (DAA), which is clinically manifested by carpal tunnel syndrome, osteoarthropathy, and the other organ involvements. For the purpose of preventing the beta 2M accumulation, the efficiency of beta 2M removal during (HPM), hemofiltration (HF), HD, and charcoal hemodiafiltration (HDF) with high-performance membranes (HPM), hemofiltration (HF), HD, and charcoal hemoperfusion was evaluated. Among 27 patients treated with these methods, significant beta 2M removal was noted in HDF with HPM and HD with polyacrylonitril (PAN) membrane. However, treatment of HDF with HPM for more than 6 months caused no remarkable improvement in clinical symptoms of patients, and serum beta 2M levels decreased in only two out of 15 patients. These results imply that beta 2M might be most effectively removed by HDF with HPM and HD with PAN membrane, but further long-term studies will be necessary to conclude whether these procedures could become successful therapeutic regimen for DAA.