To elucidate the pathogenic role of uremic toxins for anemia in patients on maintenance dialysis, the case analysis, erythrocyte osmotic fragility and serum concentration of uremic metabolites were studied, and the following results were obtained. 1) There were the patients whose hematocrit (Hct) changed along with the change of uremic toxins removal by alteration of dialysis regimen. 2) Osmotic resistance of erythrocyte in 38 hemodialysed patients was decreased and urea, creatinine and middle molecular substances had the effect on decreasing the osmotic resistance of erythrocyte in vitro. 3) There were significant inverse relationship between Hct and serum urea nitrogen levels and also serum middle molecules levels in 66 patients on maintenance dialysis. Serum creatinine and guanidino compounds concentrations tended to inversely correlate to Hct. 4) The patients on CAPD (continuous ambulatory peritoneal dialysis) had high Hct levels accompanying with low serum uremic toxins levels, especially urea and middle molecules, as compared to other dialysis regimen such as hemodialysis or hemodiafiltration. In conclusion, uremic toxins may be one of the pathogenic factors of anemia in patients on maintenance dialysis, in paticular the effect of urea and middle molecules may play an important role in it.

View full abstract

Calcium balance during hemofiltration was studied in five cases of chronic renal failure in order to determine the optimal concentration of calcium (Ca⁺⁺) in the substitution fluid. Ca⁺⁺ balance was found to be often negative when the ordinary substitution fluid with Ca⁺⁺ concentration 3.5mEq/l. was used. This tendency was observed more frequently when the pre-hemofiltration plasma Ca⁺⁺ concentration was much higher and when the water removed was much larger in amount.
Approximately 400mgs. of Ca⁺⁺ enter the body during five-hour maintenance hemodialysis using the dialysate with Ca⁺⁺ concentration of 3.5mEq/l.
The concentration of Ca⁺⁺ in the substitution fluid should be 4.0 to 4.5mEq/l., if the same amount of Ca⁺⁺ influx be expected during hemofiltration.

View full abstract

Various factors have been suggested for the etiology of toxemia of pregnancy, but the cause or causes remain obscure. Particularly, the pathogenesis of eclampsia, which is accompanied by the sudden onset of generalized tonic and/or intermittent convulsions and syncope, in complex. However, placental toxic substances, which possess a convulsion-inducing property, are thought to be one of the factors causing eclampsia, and also related to the occurrence of renal failure and disseminated intravascular coagulation (DIC) seen as the complications. Eclampsia is often associated with serious complications and the prognosis is rather poor.
It is ideal to treat the patients with eclampsia without leaving irreversible hypertension, renal failure or DIC behind. However, there has been no definitive therapy for eclampsia. Hemodialysis (HD) was actively induced for the treatment of five patients with a confirmed diagnosis of eclampsia, according to the theory that in vivo (placental?) toxic substances may be responsible for the onset of eclampsia.
Acute renal failure (ARF) developed in one patient probably because of a long gap of time between the seizure of convulsions and the induction of HD. However, the prominent improvement of clinical symptoms and signs was observed in the remaining four cases by the early induction of HD. No serious complications were noted in these patients and they were cured completely. Two other eclamptic patients were treated with the direct hemoperfusion (DHP) from a view point of the removal of toxic substances and the therapeutic efficacy was dramatic. It was especially effective in the improvement of consciousness, the prevention of serious complications and the teratment of DIC. Although the number of the patients treated was too small to conclude the therapeutic significance and appropriateness of HD and DHP in the treatment of eclampsia, they can be evaluated since no side effects were recognized and sufficient clinical efficacy was obtained. Guanidino compounds (GC), recently calling attention as contributing to uremic toxins, also possess a strong convulsive property. The analysis of GC was attempted because of the possibility of their relationship to the pathogenesis of eclampsia. However, it was impossible to detect them in the eclamptic patients. Further study is neccessary in regard to GC.

View full abstract

Recently, the cerebrovascular accident in chronic hemodialysis patients became a major cause of death in Japan. We have experienced pontine hemorrhage with extremely poor prognosis in young long-term hemodialysis patients. Therefore, we examined the Annual of the Pathological Autopsy Case in Japan in 1978 and 1979, to make sure whether pontine (brainstem) hemorrhage in dialysis patients is more common than that in general population.
Out of 62, 961 autopsy cases, 796 patients were dialysis patients, and among them, 135 patients died from cerebrovascular accident. The incidence of cerebrovascular accident in dialysis patients was 9.2 times higher than that in general population.
These 135 patients [mean age 51±13.2 (S.D.)] consisted of 80 with cerebral hemorrhage, 9 with subarachnoid hemorrhage, 12 with subdural hematoma, 2 with epidural hematoma and 32 with cerebral infarction. Sixty two brain hemorrhage, in which localization was described, consisted of 37 cerebral hemorrhages, 19 brainstem including 10 pontine hemorrhages and 6 cerebellar hemorrhages. Brainstem (pontine) hemorrhage in dialysis patients was significantly more frequent than that in general population (P<0.025). Therefore, the bleeding site of brain hemorrhage in dialysis patient was a little different from that in general population.
The result suggests that the brainstem (pontine) hemorrhage is more common in dialysis patients. The reason of frequent brainstem (pontine) hemorrhage in hemodialysis patients was discussed.

View full abstract

The diet control is one of the important factors for improving the rehabilitation rate of the hemodialysis patients.
The actual condition of the diet control in 139 patients is investigated. They are divided into 5 groups by the length of hemodialysis therapy; group A within 1 year (15.8%), group B for 1-2 years (31.7%), group C for 3-4 years (22.3%), group D for 5-9 years (25.5%), group E over 10 years (6.4%). Most of the patients intend to follow the diet restriction regardless of the length of the therapy. Especially, they are paying full attention to the weight gain which reflects overload of fluid and salt. The patients dialysed over 5 years can control fluid and salt adequately without difficulty, probably because they are accustomed to the restricted diet. About 70% of pateints within 3 years of hemodialysis suffer extreme thirst due to fluid restriction.
The percentage of such patients reduces to 40% after the duration becomes longer than 3 years. As the period becomes longer, the patients can control their weight more easily without consciousness of thirst. To prevent hyperpotassemia fruits and other high-potassium foods are restricted.
Cooking can also appreciably decrease the potassium content.
Diet intake is well on non-dialysis days. Appetite is influenced by dialysis treatment for the patients of shorter dialysis period. As the period becomes longer, the hemodialysis treatment becomes a part of their life. For the better control of diet in the patients, the cooperation of their family is important. As the hemodialysis period becomes longer, the family members gradually adapt their life to that of the patient. As a conclusion, patients in group A are making an effort in the diet control with some hesitation, in groups B and C they seem to be somewhat careless and loose due to a kind of familiarity with dialysis therapy, and in groups D and E, the patients are fully accustomed to the dialysis therapy and accept the diet restriction without confusion. For the better control of diet, the staff members must have good communication with the patients and repeat instructions regardless of the presence or absence of problems.

View full abstract

The changes in serum [Na⁺] concentration and transcellular body fluid distribution during interdialysis period were simulated. It may be important to restrict salt intake in patients undergoing high Na⁺ hemodialysis in order to keep the long term effects without positive sodium balance. The combined application of our models for both intradialysis and interdialysis is very useful to draw a whole picture of sodium and water metabolism in dialysis patients.

View full abstract

Clarifying dynamic behavior of middle molecules (MM) in hemofiltration (HF) may contribute to establishment of HF treatment. Permeability and change in serum concentration of β₂-microglobulin (β₂M) and myoglobin (Mb) were clinically studied for polymethyl-methacrylate (B1-L) (B), polyacrylnitrile (RP-6) (R) and (PAN 15) (P) membrane filters. In this experiment, two patients were studied. In those patients, averaged UFR (OF) were 95.3±7.5, 79.2±13.9 and 92.6±9.0ml/min for B, R and P, respectively. β₂M was scarcely detected in ultrafiltrate from B and P and its SC for R was 0.41±0.03. Once HF treatment was initiated, however, concentration of β₂M with B and R decreased similarly and finally reached 32±9 and 52±6% of pre-HF treatment value, which means β₂M was absorbed by B. Its concentration with P rather increased during HF treatment to 123±20% of the initial value. Concentration of Mb during HF treatment increased with P to 130±10%, where as it did not change with R and decreased with B to 44±11% of pre-HF treatment value mainly due to absorption of Mb by B. As to MM removal in HF, effect of generation rate and absorption can not be neglected.

View full abstract

Six patients with renal failure due to amyloidosis were treated by HDT. Two patients were male and four were female, and patients' age ranged from 37 to 69, mean age being 50. All of them were suffered from steroid resistant nephrotic syndrome in the early stage. The diagnosis was made by renal biopsy. One was secondary amyloidosis associated with bladder carcinoma, but the other were primary amyloidosis. At the time of admission, involvement of other oragans, such as hypotension, abnormality of ECG and hepatic dysfunction were found in some cases. The interval from the recognition of edema to the beginning of HDT ranged from 12 to 27 months. In all cases except one, HDT had to be emergently initiated because of rapid progression of cardiac failure, when plasma creatinine was below 6.6mg/100ml. In four cases, setting up of arteriovenous fistula failed because of hypercoagulability of the blood necessitating on external shunt, while development of fistula was poor in the other two cases with successful anastomosis.
In the period of HDT, complications of other organs, such as liver dysfunction, myocardial damage, inpairment of atrioventricular conduction system, involvement of gastrointestinal tract (especially anorexia), and hypotension were added. By these disorders general condition of the patients became poor and effect of HDT was diminished.
Hypotension was the most difficult problem in HDT in the patients with renal amyloidosis. Mean arterial pressure during hemodialysis was below 90mmHg in three cases, and in the other 3 cases, hypotension was observed more frequently during HD than in patients with chronic renal failure due to glomerulonephritis. In two cases, blood pressure was apt to drop after blood restitution rather than before it. There seems to be unknown causes of disregulation in blood pressure control. Duration of survival from initiation of HDT were between 10 days and 34 months. Five died, the causes were: suicide by plucking off the external shunt, liver insufficiency, cachexia, myocardial infarction and acute cardiac arrest. One is still alive on HDT, but his general condition is poor.

View full abstract

Cimetidine, 400mg a day, was orally administered to the patients on chronic hemodialysis for a 4-week period and a 6-week period to determine mainly the reduction rates of serum parathyroid hormone (PTH).
1) Changes in PTH after the short-term cimetidine therapy.
In the group with markedly increased PTH (the pre-cimetidine therapy level of PTH being 8.03±3.63ng/ml), PTH dropped significantly to 5.67±2.94ng/ml within 4 weeks, but tended to increase after the cessation of cimetidine therapy. In the group with moderately increased PTH (the pre-cimetidine therapy level of PTH being 3.36±0.88ng/ml), PTH decreased moderately to 2.56±0.66ng/ml within 4 weeks. This decrement was not significant. In the both groups, serum calcium and phosphate did not show any significant change throughout the period of cimetidine therapy, suggesting that PTH reducing activity of cimetidine was not due the secondary effect of serum calcium.
2) Changes in PTH after the long-term cimetidine therapy.
The PTH levels in 5 patients belonging to the group with markedly increased PTH were 7.66±3.91ng/ml before the cimetidine therapy, but dropped significantly to 5.17±3.05ng/ml in one month and to 3.63±1.12ng/ml 6 months after the cimetidine treatment. In the patient with abnormally high PTH level (14.39ng/ml), even a minimal dose of 1-alpha-(OH)-D₃ induced hypercalcemia promptly, thus a sufficient amount of 1-alpha-(OH)-D₃ could not be given, and the patient complained of severe bone pain. However, as the PTH level decreased with cimetidine therapy, an increased dose of 1-alpha-(OH)-D₃ did not produce hypercalcemia, and bone pain disappeared.
3) Changes in the serum cimetidine concentration and it's reduction rates during and after hemodialysis.
After the oral administration of cimetidine 200mg, the serum cimetidine concentration reached a maximal level of 1.84±0.63μg/ml in 4 hours and decreased gradually thereafter to 0.86±0.33μg/ml by 10 hours. Even after the continuous administration for 4 weeks, there were no signs of the accumulation.
The reduction rate of serum cimetidine concentration per single hemodialysis was 69.2±10.5% after 5 hours of hemodialysis using a dialyzer with a mean membrane surface area of 1.3M².
Cimetidine therapy to the patients with uncontrollable secondary hyperparathyroidsm in considered worthwhile to attempt before performing subtotal prathyroidectomy.

View full abstract