The incidence of anti-ATLA was investigated in 234 patients with chronic renal failure under hemodialysis. The results obtained were as follows. 1) The seropositivity of the patients (33.8%) was higher than that of healthy residents (11.7%) and blood donors (6.9%) in the Kagoshima district, an ATL-endemic area (p<0.01). 2) There was no correlation between the duration of hemodialysis and anti-ATLA positivity. 3) The incidence of anti-ATLA increased with the rise in the number of blood transfusions given (p<0.05). 4) The seropositivity of patients without episodes of blood transfusion was also higher than that of healthy residents in the Kagoshima district (p<0.05). The data suggested that HTLV-1 was transmissible by blood transfuion, and that therefore it seems necessary to carry out mass-screening of blood units to prevent the spread of HTLV-1 infection in ATL-endemic areas, as soon as possible. Further future studies to clarify why the seropositivity of patients without blood transfusion was statistically high may also be necessary.

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Renal biopsy was done in ten patients with acute renal failure of unknown etiology to determine the underlying histology. Their serum creatinine levels ranged between 2.5 and 11.8mg/dl and urinary protein excretion was between 0.9 and 26mg/day.
Histological diagnoses were as follows: crescentic glomerulonephritis in 5 patients, necrotizing glomerulonephritis in 2, acute interstitial nephritis in 2, and diffuse endcapillary proliferative glomerulonephritis in 1.
Based on histologic findings, high-dose steroid therapy was tried in 7 of 10 patients. Six of 7 patients given steroid therapy either improved markedly or recovered from acute renal failure. The only complication was massive hematuria noted in a 65-year-old male, and this was controlled by renal arterial embolization.
It was concluded that renal biopsy was of value in patients with acute renal failure of unknown origin to help in deciding on treatment and estimating prognosis.

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Frequency of premature ventricular contractions (PVC), total hourly cardiac beats (TCB) and variations in heart beats (VHR) were studied in patients with chronic renal failure undergoing long-term CAPD by means of Holter ECG recording. Subjects consisted of 20 patients (15 males and 5 females, mean age 48 years). The average duration of CAPD in those patients was 16±13 months. Among them, 13 patients had hypertension, and 10 had left ventricular hypertrophy. Other cardiovascular complications included 3 cases of coronary insufficiency, and one each of complete right bundle branch block, old myocardial infarction, ventricular septal defect and hypertrophic cardiomyopathy. During the observation period no symptoms related to the cardiovascular system were noted.
TCBs were the highest in the daytime and the lowest at midnight (5, 393±815beats/h and 4, 526±725beats/h, respectively). Althuogh this pattern resembled that of healthy persons, there was a tendency for the TCBs to be increased. VHR seemed normal except for a certain period in which the variation was small.
Eleven patients demonstrated PVCs; however, none of them had critical, frequent, multifocal, ectopic beats or R-on-T phenomenon. Decreases in TCB and VHR were observed in some aged or diabetic patients. On the other hand, their day-and nighttime patterns were close to normal, and the frequency of PVC was not siginificantly high.
Manipulations of daily dialysate exchange had minimal influence on the cardiovascular system in patients under CAPD. We have thus concluded that CAPD is useful, particularly in uremic patients with cardiovascular complications.

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Since the first description of aluminum-related encephalopathy in patients on regular dialysis treatment, the toxicity of aluminum has been well recognized. Other aluminum-related diseases such as vitamin D-resistant osteomalacia and microcytic anemia have also been reported. In the present study, hydrous cerium oxide, a rare earth compound, was investigated as a new non-aluminum phosphate binder, Cerium oxide and hydroxyaluminum were mixed at the ratio of in a solution of phosphate compounds in which the phosphate ion concentration was 2.0mM, and the solution was stirred for one hour. Cerium and aluminum were also compared around the neutral range. The adsorptive effect of cerium oxide was one-fourth as great as that of hydroxyaluminum.
We tested the adsorptive effects of cerium oxide by using bovine blood 500ml, phosphate concentration 7.05mg/dl. Bovine blood was allowed to flow directly through a cerium oxide column. The adsorptive effect continued up to 90 minutes and the serum concentration reached zero at 120 minutes.
We also fed cerium oxide to partially (5/6) nephrectomied rats, chronic renal failure models, comparing it with hydroxyaluminum. In the cerium group, serum phoshate declined significantly from 7.02±0.92 (mg/dl) to 4.98±0.64 (mg/dl) (p<0.01) after two weeks' feeding, and in the aluminum group it also declined from 6.92±0.82 (mg/dl) to 5.24±0.70 (mg/dl). In conclusion, cerium oxide proved to have stronger adsorptive efficacy against phosphate ion than hydroxyaluminum.
A phosphate binder to take the place of aluminum gel is urgently needed, and cerium oxide is worth being studied and tested further.

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The interbeat interval response of Valsalva maneuver was significantly lower in hypotensive than normotensive or hypertensive hemodialysis patients (hypotensive (1.22±0.12): vs normotensive (1.40±0.11; p<0.01; or hypertensive (1.35±0.06; p<0.001). Overshoot in arterial pressure after Valsalva maneuver was observed in 1 of 10 hypotensive, 5 of 7 normotensive and all 8 hypertensive patients. These results suggest that baroreflex dysfunction is more significant in hypotensive than normotensive or hypertensive patients.
In order to evaluate the abnormal site of the baroreflex arch, cold pressor test, clonidine test and motor nerve conduction velocity were examined in these hemodialysis patients. The changes in mean arterial pressure by cold pressor test (ΔMAP: mmHg) were 10.86±4.41mmHg in the hypotensive, 12.60±7.27mmHg in the normotensive and 21.20±15.25mmHg in the hypertensive patients. These data were not significant compared with 14.92±5.71mmHg in control subjects. Clonidine induced depressor responses in the hypotensive patients; thus it would be working as an α₂ adrenoreceptor agonist. Motor nerve conduction velocity was delayed in the hypotensive in comparison with the normotensive and hypertensive patients. These results suggest that hypotensive patients undergoing long-term hemodialysis have baroreflex dysfunction because of abnormal response by Valsalva maneuver but no abnormalities in cold pressor test or clonidine test, indicating intact efferent and central sympathetic activity. However, motor nerve conduction velocity was slightly delayed in the hypotensive patients. The mechanism of hypotension in long-term hemodialysis appears to be multifactorial, and further studies, including surveys of the afferent pathway and vascular reactivity, will be necessary.

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We have proposed a new method for continuous hematocrit measurement and developed a hematocrit meter using optical devices; an LED and photo-transistor.
This optical hematocrit meter (Hct meter) can estimate the blood volume transition during HD treatment. The reduction rate of blood volume and plasma refilling rate could also be estimated with a simplified state observer system. Combined with a UFR controller, this Hct meter will be helpful in controlling the blood volume transition so as to prevent hypovolemia during short-term HD.

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The alkalizing and metabolic effects of acetate and lactate were compared in 12 chronic renal failure patients under maintenance acetate HD and/or HF with lactate replacement through analyses of acid-base balance and measurements of plasma lactate, pyruvate and acetate levels. To measure the plasma acetate concentration, a new gas chromatographic technique was used. In this technique, Unisol-F 200 for column packing and 2% sulfosalicylic acid for deproteinization were used. In comparing plasma pH and bicarbonate concentrations pre-and posttreatment, no significant difference was noted between the acetate HD and lactate HF groups.
A significant increase of plasma pyruvate (p<0.01) and lactate (p<0.01) after treatment was observed late in lactate hemofiltration (lactate: 1.2±0.24mM/l to 5.90±2.49ml; pyruvate: 0.08±0.01mM/l to 0.11±0.07mM/l). Plasma acetate also rose significantly after acetate hemodialysis (p<0.01; 0.10±0.06mM/l to 3.34±2.23mM/l). Blood lactate and pyruvate in acetate HD and blood acetate in lactate HF were not significantly changed during the course of treatment.
Gonzalez et al observed an increase of plasma lactate at the end of acetate HD and suggested that a portion of the acetate anion follows the anaerobic glycolic pathway in a retrograde fashion. In the present study, there were no significant changes in plasma lactate levels before and after acetate HD, in addition, plasma acetate levels during iactate HF were not significantly altered. These results suggest that a retrograde anaerobic glycolic pathway is not significantly operated in acetate HD, and there seem to be no significant metabolic pathways from lactate to acetate or acetate to lactate.

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Hyperpotassemia is often encountered in regugarly hemodialyzed patients. However, excessive potassium (K) intake does not always cause it. To evaluate the K homeostasis in chronic dialyzed patients, we measured the amount of K removed by hemodialysis (HD) as well as the erythrocyte K concentration (RK) before and after HD. The mean value of K removed by HD was 56.0±10.4mEq (11.9-259.5mEq). The amount of removed K showed linear correlation with the serum K concentration before HD and the K concentration difference before and after HD (Y=31.9X-96.5, r=0.59, p<0.01, Y=41.7X+1.43, r=0.55, p<0.01, respectively).
RK was 94.8±4.3mEq/l cell before HD and 93.3±3.9mEq/l cell after HD. These values were significantly lower than that in normal subjects, but were not significantly different from each other. The change of RK by HD and the difference between measured removed K and estimated removed K, which was calculated by the change of serum K concentration by HD, showed a significant statistical correlation (Y=0.46X-0.73, r=0.69, p<0.01). These data showed that in some chronic hemodialyzed patients, K entered into the intracellular space during HD, while in others, K was removed from the intracellular fluid by HD.
Thus, we conclued that it might be questionable to estimate the K homeostasis only by the change of plasma K concentration during HD.

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To determine the adequate treatment for peritonitis complicating CAPD, we examined serum levels and clinical effects of the intraperitoneal administration of antibiotics, either latamoxef (LMOX) or cefoperazone (CPZ).
We added the antibiotics, 2.5g/2-liter of dialysis solution, to all exchanges. With the first administration, the sarum concentration of the antibiotics increased to adequate levels (mean of 10.4μg/ml for LMOX and 7.5μg/ml for CPZ) to prevent bacteremia.
During subsequent administrations, we maintained a high serum level of LMOX, 43-46μg/ml, and a lower level of CPZ, 8-16μg/ml, with the exception of two cases of liver dysfunction receiving CPZ, in whom the range was 25-47μg/ml, After cessation of the drugs, the serum concentration of CPZ decreased more quickly than that of LMOX.
These results suggest that CPZ is mainly eliminated by the bile or metabolized by the liver, and serum LMOX levels are higher than CPZ during use in CAPD patients who can hardly eliminate drugs by urinary excretion.
Whether we used LMOX or CPZ, white blood cell counts in dialysate decreased to less than 10/mm³ in five or six days. The LMOX treatment group seemed to respond more quickly than the CPZ group, but the difference achieved no statistical significance.
In the treatment of CAPD peritonitis, careful selection of antibiotics and adjustment of dosage should be undertaken in due consideration of their elimination site, the liver or kidney.

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We investigated the adequate nutritional requirements of hemodialysis patients, since 50% of our patients were obese. Twenty-five patients were divided into 2 groups according to standard body weight, thus: Group A: over standard body weight, Group B: under standard body weight. These groups were each recommended to take a low-calory diet (1, 600kcal, Protein: 80g) and a hig h-calory diet (2, 400kcal, Protein: 90g), respectively. After one year, it was found that 43% of patients in group A had been able to decrease their body weight and that 45% of patients in group B had been able to increase their body weight. Most of the biochemical perameters followed in these patients were stable, including urea nitrogen, creatinine, albumin, total protein, hemoglobin and transferrin.
It was concluded that calorific intake should be adjusted according to standard body weight, age and exercise and that it may be important to maintain the body weight within the standard range.

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Foreign particles contaminating hemodialyzers have a possible risk of causing microembolism and allergic reactions in hemodialysis patients. We investigated the size distribution of particles, and the effects of both striking the headers of dialyzers and the flow rates of the rinsing saline on the elimination of foreign particles from dialyzers. Some of the saline used for rinsing was filtered through a Millipore filter before microscopic examination for foreign particles. We also checked changes in the particle counts during 5h of continuous flow using a blood pump. The diameter of the majority of contaminating particles was around 3.5μm. We therefore counted particles with diameters of more than 3μm, in order to monitor the washing efficiency of dialyzers. During the rinsing of dialyzers, particles were effectively eliminated by striking the headers of the dialyzers. We found that striking should be started immediately after the blood line had been filled with saline, and that the flow rates (350-700ml/min) of saline did not affect the rinsing efficiency. By filtration of used saline, we found particles, mostly ranging in size from 5μm to 200μm, with many kinds of shape and color. Among them were fibers which were several millimeters long. Once dialyzers had been rinsed effectively, there were no increases in particle counts in a closed circuit which consisted of a dialyzer and a blood line. In order to rinse dialyzers effectively, at least one liter of saline is necessary, and striking the headers of the dialyzers throughout the rinsing procedure is important.

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Hemodialysis patients often complain of gastrointestinal symptoms such as nausea, vomiting and constipation.
Gastric emptying was measured in 23 hemodialysis patients (11 diabetics, 12 non-diabetics), and small bowel transit time in 16 hemodialysis patients (8 diabetics, 8 non-diabetics).
The method of Heading and Harasawa et al., i.e., the 45-minute value of acetaminophen, was used for estimation of gastric emptying. Acetaminophen concentration was measured according to the method of Routh et al. using the dye method. The values obtained were 11.2±1.6μg/ml (mean±SE) in normal controls, 8.9±1.3 in non-diabetics and 5.5±0.9μg/ml in diabetics. A significant difference was observed between diabetics and nondiabetics (p<0.05). The decreased gastric emptying in diabetics might be attributed to diabetic autonomic neuropathy. Aclatonium napadisilate (Abovis^®), an agent for activating digestive function, was administered to 8 diabetics in order to examine gastric emptying time. After the administration of Abovis^®, gastric emptying was speeded up significantly (p<0.05), suggesting that Abovis^® was clinically effective. Hemodialysis was performed on 5 patients following acetaminophen measurement. The acetaminophen concentration was lower after dialysis than before dialysis. None of the patients showed hepatitis after the administration of acetaminophen.
According to Bond and Saito et al., small bowel transit time measured by the concentration of pulmonary H₂ exhalation with lactulose showed no difference between normal controls and non-diabetics ordiabetics [80±10min, (mean±SE), 85±10min and 82±9min, respectively].
To evaluate the effect of dialysis, small bowel transit time was measured in 3 patients 1 hour after the start of dialysis. Transit time in one patient remained unchanged at 60 minutes and in the 2 other patients it showed a delay of 10 minutes.
Both gastric emptying and small bowel transit time were measured in 3 non-diabetics and 6 diabetics, but no correlation was observed between the two measurements.

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Carpal tunnel syndrome and joint problems such as shoulder pain, knee joint pain and trigger fingers are major complications among patients on long-term maintenance hemodialysis.
Carpal tunnel syndrome was observed in 22.1% (17/77) of patients on hemodialysis for 10 or more years. The patients with this syndrome also frequently had trigger fingers (59.1%), shoulder pain (68.2%), or knee joint pain (77.3%).
Amyloid deposition within the synovium and tendon was demonstrated in all of the operated patients with carpal tunnel syndrome. These deposits were found not only in the synovium of the carpal tunnel but also in the synovium of the knee joint, in ruptured extensor digital tendons and in rectal arterial walls in some cases. By histochemical examination this amyloid exhibited reactivity with antibodies to β₂-microglobulin and P component, but did not react with any other previously known amyloid proteins.
The high concentration of serum β₂-microglobulin in patients on hemodialysis is likely the most important causative factor in amyloid deposition. Elimination of β₂-microglobulin by hemofiltration, low-volume glucocorticoid therapy and local inunction of dimethyl sulfoxide seemed to be effective in relieving joint symptoms.

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Forty-six cases (4.0%) of malignant tumor were found among 1, 152 patients (735 male, 417 female) undergoing dialysis at the Kidney Center, Sendai Shakaihoken Hospital, or its subsidiary hospitals, during the period from January 1969 through December 1984. Of these 46 cases, 28 (3.8%) were male and 18 (4.3%) were female. This rate was significantly higher than that of the Miyagi-ken district control group (p<0.01) obtained from the life table.
As many as 48% of the malignancies were found in the digestive tract: 13 gastric carcinomas, 3 esophageal carcinomas and 6 colon carcinomas. The other affected organs and the number of patients were as follows: thyroid 7, bladder 4, uterus 4, skin 3, liver 1, pancreas 1, breast 1, lung 1 and parotid gland 1. There was one case whose primary affected organ was not defined.
In 9 patients (20%), malignancies were found within a year from the beginning of maintenance dialysis; while in 18 patients (37%), the malignancies were found more than five years after the start of dialysis. The mean dialysis period of these patients was three years and eleven months.
31 out of 46 patients underwent surgical treatment and satisfying results were obtained.

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Dialysates currently used are supplied as 35× concentrated liquids. If supplied as a one-durg powder, there would be a great advantage in transportation and storage. In order to supply dialysates as a drug powder, we must solve the deterioration such as by deliquescence of the electrolyte compound, and non-homogeneity of each electrolyte ion in the preparation.
Acetic acid-added powder for bicarbonate dialysis (KL-D) supplied by Tomita Pharmaceutical Co. is a one-drug powder that solves the above-mentioned problem. We investigated the stability, clinical efficacy and safety of this powder.
31 dialysis patients in a stable period were investigated by cross-over method using Kinderly AF-1P as a comparison.
Some differences were observed between the two dialysate compositions in pH, electrolytes, etc. The data presented no problems in terms of clinical use, and no appreciable difference was observed in the change with the lapse of a day or longer between the two dialysates. According to clinical tests, significant differences were observed in serum sodium, serum chloride, serum magnesium, osmotic pressure of blood plasma, and base excess. But these were all in the normal region and no significant differences were observed in other test data. Also no significant difference was observed in the apparent frequency of clinical symptoms between the two dialysates.
From the above results, the conclusion was obtained that KL-D has an effect equivalent to AF-1P in dialysis, and the former is a more stable and safer dialysate.

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