We developed a too-pool kinetic model for β₂-MG consisting of interstitial and plasma space and simulated the serum β₂-MG concentration trends in patients with end-stage renal failure on hemodialysis for a long period of time. In this model, we supposed that 1) the generation rate would not change even if the β₂-MG concentration fluctuated and 2) β₂-MG degradation rate within the body between treatments was culculated as the product of the β₂-MG concentration and time independent intrinsic clearance and further, 3) during an intermittent treatment β₂-MG degradation rate was culculated as the product of the β₂-MG concentration and the artificial kidney clearance plus 2). The results showed that a dramatic fall of serum β₂-MG level could be expected right after treatment, however, a gradual rise of serum concentrations, which we call a rebound phenomenon, is observed between treatments. Asuming that a dialyzer clearance for β₂-MG is 50ml/min and 4 hour dialysis is performed 3 times a week, estimated pre-dialysis serum levels of β₂-MG after 2 weeks in patients with initial serum levels of 60, 40, and 20ml/l are 39.2, 30.8 and 18.4 mg/l, respectively, due mainly to the above mentioned rebound phenomenon. This means that a continuous fall of the serum concentration could not be obtained by a present method of intermittent hemopurification especially in patients with relatively lower serum β₂-MG level among HD patients.

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In order to elucidate the relation between dialytic amyloidosis and cystic radiolucency (CRL), we studied factors such as age, history of dialysis, disorder underlying chronic renal insufficiency, Ulnar variance, and hemato logic parameters by dividing CRL of carpal bones into 4 groups. Multivariate analysis was used to show effects of cyst forming factors. Subjects were 150 patients (85 males and 65 females of 53.5 years receiving dialysis for 71.9 months. Healthy 6 adults (13 males and 23 females) were selected as controls. Positive CRL was significantly more frequently found in the patients (34.7%) than in the controls (19.4%). The incidence in patients with complicating carpal tunnel syndrome was 87.5%. Mean onset age tended to be older with more serious CRL. Dialysis period was significantly longer in group 4 but no significant differences were found among the three remaining groups. Patients receiving dialysis for 6 or more years significantly more frequently showed positive CRL than the controls and those receiving for less than 6 years did insignificantly. No constant trend was found between CRL and ulnar variance. As to hematologic parameter, serum Ca level greatly contributed to classification of CRL and tended to rise more when CRL was more serious whereas serum β₂-microglobulin did not. From the above, it is Concluded that amyloidosis should be diagnosed in patients of Group 4 (having 3 or more radiolucent sites) treated for 6 or more years, in principle.

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We conducted a large-scale investigation of abdominal disease in maintenance dialysis patients. The investigation covered 1404 cases who underwent upper gastrointestinal tract examination in our hospital in the 5 years since 1983 and 634 cases who underwent abdominal ultrasonic examination in the 2 years since 1986. Upper gastrointestinal fluoroscopy was conducted in 55.5% all the total cases during the 5 years and upper gastrointestinal endoscopy was performed in 30.7% of the cases with abnormal findings. In the 5 years we diagnosed 30 cases (3.9%) of gastric ulcer, 44 cases (5.6%) of duodenal ulcer and 2 cases (0.3%) of early gastric carcinoma. Abdominal ultrasonic examination was performed in 70.3% of all cases in the 2 years. We also diagnosed 34 cases (7.6%) of gall stones, 15 cases (3.4%) of gall bladder polyps and 1 case (0.2%) of hepatocellular carcinoma.
It is important to investigate periodically the abdominal diseases of maintenance dialysis patients, who are often asymptomatic.

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Polymorphonuclear neutrophil elastase (PMN-E) has been shown to increase during hemodialysis (HD). To determine the factors which influence the increment of PMN-E, 37 hemodialyzed patients were studied. PMN-E levels in plasma obtained before and after HD were measured by enzyme immunoassay. There was no significant difference between the DM Group (n=12) and non-DM Group (n=25), nor was there any significant difference between the short HD duration Group (less than 3 months, n=24) and the long HD duration Group (more than 5 months, n=13).
As far as the dialyzer membrane was concerned, there was no significant difference between 15 patients treated with regenerated cellulose membranes and polymethylmethacrylate (PMMA) membrans. Nor was there any significant difference between 18 patients treated with heparin and FUT-175 (nafamostat mesilate).
When the effects of vitamin D₃ (Vit D₃) and calcium bicarbonate on PMN-E levels were evaluated, combined use of Vit D₃ and calcium bicarbonate seemed to depress the PMN-E elevation rather than use of calcium bicarbonate alone or no usage of these agents at all.
There was no significant correlation between serum calcium levels and PMN-E levels in any of the cases. However, there were strong correlations between elevations in serum calcium and PMN-E in 3 of the cases.
From these results, it appears that alteration of serum calcium levels and certain agents, such as Vit D₃ and calcium bicarbonate, might be involved in the mechanism of PMN-E elevation during HD.

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Plasmaα-ANP (atrial natriuretic peptide) was determined in 26 chronic hemodialysis patients on two consecutive occasions, on inter-dialysis as well as dialysis days, and date were analyzed in relation to weight gain from estimated dry weight, mean arterial pressure (MAP) and plasma renin activity (PRA), and its effect on the control of blood pressure was investigated.
In cases with weight gain of more than 3% of dry weight, plasmaα-ANP revealed a significant increase that was correlated with % weight gain (r=0.662, p<0.001).
On the other hand, no suppression of MAP by α-ANP was seen in patients with PRA higher 2.5ng/ml/hr or less than 2.5ng/ml/hr.
Therefore, we concluded that although plasmaα-ANP increased significantly in HD patients accordind to % weight gain, it exerted no physiologic effect on the regulation of blood pressure.

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The incidence of malignancy in patients with chronic renal failure has increased recently in accordance with the prolongation of dialysis.
Routine serological screening for malignancy has been applied in dialysis patients, but abnormal values have not been defined. Therefore values in patients with chronic renal failure not complicated with malignancy should be determined for the clinical application of tumor markers.
Seventy-four patients (17 with chronic renal failure not on dialysis, 30 on hemodialysis and 27 on CAPD) participated in this study.
CEA, TPA, AFP, EL1, CA125, CA19-9 and γ Sm were determined by radioimmunoassay or enzymeimmunoassay and compared with values obtained from 81 healthy controls.
CEA, TPA, AFP and EL1 were significantly higher in patients with chronic renal failure. No patients with chronic renal failure were positive for CA125. But CEA, TPA and AFP were significantly higher in patients on hemodialysis than in those not recieving dialysis, However there was no significant difference between hemodialysis and CAPD.
The radioimmunoassay applied to tumor markers in this study was not infuluenced by uremic substance, The reason for the higher values might be delayed removal from the blood stream due to impaired renal function.

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To elucidate the effects of recombinant human erythropoietin (r-HuEPO) on exercise tolerance, we performed exercise tests in 25 patients on chronic maintenance hemodialysis treatment.
r-HuEPO was given to every patient with hematocrit<25% and an exercise test with a bicycle ergometer was perfomed before and after r-HuEPO therapy.
Blood pressure, heart rate (HR) and rating of perceived exertion (RPE) were measured at rest and during the exercise test. In addition, hematocrit, lactic acid, creatine phosphokinase (CPK), pH and blood gases were measured in every patient by arterial blood sampling at rest and immediately after stopping the exercise.
The results were as follow:
1) Hematocrit increased from 22.7±1.5% to 29.0±2.2% (P<0.001).
2) HR decreased at each step during the exercise test after r-HuEPO treatment (P<0.01-P<0.001).
3) RPE decreased at each step during exercise test after r-HuEPO treatment (P<0.05-P<0.001).
4) The percentage of patients who accomplished the exercise test increased from 63% to 96% after r-HuEPO treatment.
5) The lactic acid level after the exercise test decreased from 19.2±10.0mg/dl to 15.6±5.8mg/dl after r-HuEPO treatment (P<0.05).
6) The CPK level at rest decreased from 98.0±49.3 IU/l to 87.3±58.2 IU/l after r-HuEPO treatment (P<0.05).
7) A higher resting level of CPK was found in patients who dropped out of the exercise test before r-HuEPO treatment.
8) No significant differences in resting CPK levels were found before and after r-HuEPO treatment in patients who accomplished the exercise tests.
9) No significant differences in pH, PaO₂, and PaCO₂ levels were found before and after r-HuEPO treatment.
These findings suggest that r-HuEPO treatment improved exercise tolerance in MHD patients. The results may have been caused by improvements in anaerobic metabolism, muscle ischemia and cardiovascular circulation.

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Autonomic functions in patients with chronic renal failure (CRF) were assessed by means of digital plethysmography designed for evaluating both sympathetic and parasympathetic functions. The subjects consisted of 68 patients with CRF due to chronic glomerulonephritis (62 cases). Polycystic kidney disease (3 cases), pyelonephritis (2 cases) and gouty kidney (1 case), excluding all those of SLE or DM origin. The patients were subdivided into five groups: Predialysis group (17 cases), Hemodialysis group (HD, 17 cases), Continuous ambulatory peritoneal dialysis group (CAPD, 18 cases) and 3 cases of kidney transplantation. One-hundred-sixty-six healthy controls were also chosen for the study. Optical plethysmography was recorded for 2 minutes from the second finger of the right hand in a quiet room, and the data was digitally analyzed for the coefficient variation of wave heights (CV_WH) and pulse-pulse intervals (CV_PP).
CV_WH and CV_PP were 7.44±3.58% and 2.41±0.94% respectively in the predialysis group, 7.57±4.04% and 2.29±0.76% in the HD group, 6.69±2.96% and 1.96±0.83% in the CAPD group and 8.20±1.92% and 3.70±1.32% in the transplanted group. CV_WH in each group of CRF patients were significantly decreased as compared with agematched control values. CV_PP in dialyzes patients were also decreased significantly as compared with control values. No significant difference was found between the predialysis group and normal controls. There was a positive linear correlation between CV_WH and CV_PP in the group of patients with CRF and HD. From the above results it is suggested that CV_WH and CV_PP are significantly decreased in CRF, implying the presence of both sympathetic and parasympathetic dysfunction. It is concluded that dysautonomia as observed in CRF is resistant to dialysis therapy, since no difference in the two parameters was found in the predialysis and dialysis groups and also as both sympathetic and parasympathetic nerve functions were simultaneously affected.

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Many researchers have recently reported that dioxin-like immunoreactive substances (DLIS) are detected in patients with renal failure or others who have never received dioxin. We investigated DLIS in chronic renal failure using the fluorescence polarization immunoassay method (TDX Digoxin II; Dainabot Laboratories).
DLIS in excess of 0.4ng/ml was found in five of 50 hemodialysis (HD) patients, Four of the five patients had hepatic dysfunction (Case 1: cirrhosis+heatoma; Case 2: irrhosis; Case 3: acute liver damage; Case 4 drug-induced hepatitis). Cases 1, 2 and 3 died within a month after DLIS was detected. Endogenous DLIS is thought to be a prognostic marker.
The concentration of DLIS in case 4 was decreased by plasmaperesis, and she is now alive. DLIS was also detected in case 5 with normal hepatic function. On his own, this patient had been taking a herbal medicine sold over the counter for about two years. Since DLIS decreased to under 0.2ng/ml after stopping the herbal medicine, this drug was thought to be the cause of DLIS.
High DLIS (>0.4ng/ml) was detected in four (cases 1-4) of 9 patients with hepatic dysfunction (44%). Therefore, if dioxin is administered to patients with renal failure and hepatic dysfunction, one must be careful of the effect of DLIS on the digoxin concentration.

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Since 1978, 3 cases of spontaneous intestinal necrosis in hemodialysis patients have been treated in our hospital. The patients showed several common peculiarities. The patients, who had a history of hypotension and abdominal discomfort probably caused by mass removal of fluid during hemodialysis, showed sudden onset of acute abdominal pain without bloody stool soon after dialysis. Laparotomy revealed fecal peritonitis due to perforation of the intestinal wall, which showed segmental necrosis. The necrosis was localized at the right side of the colon or the terminal ileum, although ischemic colitis is generally recognized on the left side of the colon. In spite of the absence of obvious vascular occlusion in the mesenterium, histological study of the resected intestine showed segmental necrosis with perforation and extensive submucosal congestion and fresh venous thrombosis in the area of the border of necrosis. Within a month after surgery, two patients died of intestinal perforation recurring on the oral side.
Insufficient blood flow in the intestinal vessels caused by hypotension and high blood viscosity are suspected to be common causative factors in this disease. Correction of the hypotension and anticoagulative treatment are suggested in the management of such cases.

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In 527 hemodialysis (HD) patients in January 1988, serum anti-human T-cell lymphotropic virus type-1 (HTLV-I) antibody was measured using particle agglutination (PA) and Western blot (WB) methods. The results were compared with those in 332 patients in May 1984 and 407 patients in May 1985. Changes in the number of PA-positive patients in 1984, 1985 and 1988 were also evaluated. Since November 1986, screening for anti-HTLV-I antibody has been conducted by the Japan Red Cross on donated units of blood products. The number of patients converted from seronegative to positive, was also compared before and after the initiation of screening of donated blood. The following results were obtained:
1. In January 1988, 36 of 527 HD patients (6.8%) showed a positive PA test result. The corresponding rate was somewhat higher, 10.2% in May 1984, and 6.4% in May 1985, with no significant difference being found between that in January 1988. A positive PA reaction almost never reverts to negative.
2. In the 36 patients with a positive PA reaction in January 1988, WB analysis was performed. A positive WB response was noted in 30 patients yielding an overall rate of positive reaction of 5.7% (30/527).
3. Between May 1985 and January 1988, the PA response converted from negative to positive in 5 patients. In 2 of these 5 patients, the WB was also positive. In each of these patients, the conversion from a negative to a positive reaction was probably the result of a blood transfusion prior to November 1986.
4. In 3 of these 5 patients, the WB result was equivocal. Further studies, with a long follow-up period will be necessary to evaluate patients with a low titer PA response and an equivocal response in the WB test.

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Peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) is generally due to bacterial infection. However, some patients exhibit sterile peritonitis.
Among 9 patients currently undergoing CAPD, we encountered one case of eosinophilic peritonitis in a 55-year-old male. The effluent dialysate became cloudy on the 19th day after starting CAPD. There was no abdominal pain or fever. Repeated culture of the dialysate revealed no bacteria or fungi. He had a high eosinophil count in the effluent dialysate with peripheral eosinophilia. With a diagnosis of eosinophilic peritonitis, administration of antibiotics was stopped and he improved spontaneously.
The etiology of eosinophilic peritonitis remaines to be determined, although it is thought to be related to an allergy to some constituents of the peritoneal dialysis system. Fortunately, eosinophilic peritonitis has a benign course and resolves spontaneously. Differential white cell counts of the dialysate should be performed in sterile and asymtomatic peritonitis in patients on CAPD. In patients with eosinophilic peritonitis, antibiotics should not be used to prevent opportunistic infection.

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The primary problem in furthering kidney transplantation in Japan in that of secuing kidney donors. Thus, upon visiting Oyama-cho, Shizuoka, which has the highest number of eye donor registrations and the highest percentage of eye donations in Japan, we investigated the creative activities underway in this town.
The activities in the town center on the Lion's Club. The Oyama Lion's Club has been promoting an eye donation campaign since 1970, which includes, in addition to enthusiastic education in the town, notifying surgeons of offers of eyes, arrangement for transportation, funerals for eye donors, conveyance of acknowledgements to the bereaved families and maintenance of continued communicaton with them. Thus the club places importance on communication with the town's people.
Consequently, the concept of eye donation has been spread throughout the town, where many are inclined to think it natural to donate eyes, although there is some reluctance.
We think that the shortage of kidney donors in Japan can be ascribed mostly to Japanese views on life, death and morality, as well as sentiments including a traditional reverence for the dead. This sentiment of the Japanese does not seem to be changing. We believe that the primary problem in increasing kidney donors lies in changing this Japanese value. Having carried out a survey in Oyama-cho, we were convinced that such values can be changed gradually, until they are similar to those in Europe and America by enthusiastically promoting new ideas and educating the people. Such activities should be directed to establishing community promotional systems and sincere aftercare.

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The present study was undertaken in rats to clarify factors contributing to the myocardial deposition of calcium oxalate in chronic renal failure. A simple increase in plasma oxalate levels produced by injection of sodium oxalate did not cause deposits in the heart, nor did increased levels of plasma ionized calcium appear to be important. However, the absence of renal mass (bilateral nephrectomy) caused a minimal degree of oxalate deposition in many organs including the heart, lasting for only two days. The kidney may be likened to a selective sponge that accommodates most of the crystalized oxalate. Bilateral nephrectomy could therefore lead to precipitous oxalate crystallization in other tissues. Although oxalate deposits were hardly seen in the rat's own healthy heart, following heterotropic cardiac transplantation a much larger deposition of crystals was identified in the heart allograft which was histologically damaged by rejection. This finding suggests that the state of local tissue is a much more important factor in the deposition of oxalate crystals.

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Although pancreatic lesions are known to be relatively common in patients with chronic renal failure, there have been few reports of acute pancreatitis in long-term hemodialysis patients in Japan. We observed acute pancreatitis in three of 177 patients in long-term hemodialysis (mean; 5.8 years, range 0.5-17 years) during an eight-year period. The underlying cause of chronic renal failure was chronic lomerulonephritis in all cases. In all patients, the diagnosis of acute pancreatitis was established on clinical grounds (nausea, vomiting, epigastralia, fever), elevated serum amylase level (amylase>700SU, pancreatic isoamylase>80%) and enlarged pancreas on sonography. Two patients required daily intravenous hyperalimentation and short-time hemodialysis (5 and 7 days). All patients received antibiotics and protease inhibitors. Two patients recovered completely and one died from cardiac failure 11 days after the relapse of acute pancreatitis. Possible etiological factors were hypercalcemia (2 cases) and hyerparathyroidism (1 case). The association between pancreatitis and chronic renal failure is discussed.

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Acquired cystic disease of the kidney (ACDK) has been frequently noted among adult patients treated with long-term dialysis. This association has not been well studied in the pediatric population and there have been only a few related papers published so far. We evaluated the incidence of ACDK in 15 pediatric patients treated in our hospital. Fifteen patients (9 males and 6 females) with chronic renal failure being treated with hemodialysis were studied with ultrasonography and/or CT scan. The mean age when dialysis was initiated was 13 years and 10 months. Patients had been dialyzed for a mean of 7 years.
Four patients (26.6%) had no cysts, two (13.3%) had solitary cysts and nine patients (60%) had bilateral multiple cysts (ACDK). Duration of dialysis therapy was greater in patients with ACDK (105.1±38.8 months) compared to those with solitary cysts (65.5±14.5 mo) or no cysts (46.5±21.2 mo). All patients who had undergone dialysis for more than seven years had ACDK. A sex difference was noted with there being a higher incidence among males (males: 7/9, females: 2/6). ACDK frequently occurs in children treated with long-term dialysis. Neoplasm formation in one of the complications of ACDK, and routine screening of pediatric patients who undergo dialysis may be necessary.

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A 47-year-old man on maintenance hemodialysis developed progressive swelling in the left upper half of his body after an arteriovenous fistula was made in his left arm. Venography showed obstruction of the subclavian vein and rich collaterals. Binding of the fistula resulted in rapid recovery of the various signs of swelling

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A 61-year old man was introduced to our clinic for hemodialysis because of chronic renal failure. After admission, he suffered from acute hepatitis and pneumonia, but soon recovered. One month later, high fever, general fatigue, and icterus appeared. CT showed liver abscess in the right lobe. He was treated with antimicrobial drugs, and US guided abscess drainage was performed. Two months after drainage, the liver abscess disappeared and the drainage tube was removed. He was discharged and is now being treated with chronic hemodialysis. There has been no recurrence.

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