In order to investigate the pathogenesis of anemia in hemodialysis patients, various hydrolytic enzyme activities were measured in serum of 37 patients as well as of 18 control subjects. These activities were related to other clinical parameters and were analyzed with multivariate statistical methods. The results demonstrated the importance of neutral RNase, Tryptophan-aminopeptidase, BUN as accelerating factors of anemia. On the contrary, serum creatinine level, total serum protein concentration and cathepsin C were important inhibitory factors of anemia, suggesting that they are nutritional parameters of the hemodialysis patients. These metabolic factors, as a whole, proposed 60% statistical contribution in pathogenesis of anemia on the condition of the present study.

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Anemia of patients under maintenance hemodialysis in our center has improved annually for the last eleven years.
Analyses revealed that this improvement was produced by (1) rationalized managements of patients with chronic renal failure and resultant institution of hemodialysis therapy in adequate time (2) improvement in efficiency of dialyzer, dialysis technics and water treatment (3) increase of dialysis-quantity and-frequency (4) more strict criteria for blood transfusion (5) accurate and working knowledge of diet therapy (6) various supplemental therapies for improving anemia etc.
However, it must be kept in mind that about 10% of patients in our center, which has been taking care of about 70 patients, showed Hct less than 20% and moreover hematological conditions of hemodialysis patients were easily influenced even by minor factors to ordinary people.
Iron deficiency is a frequent complication in maintenance hemodialysis patients and therefore supplemental iron therapy has become routine for our patients. Intravenous iron administration resulted in a remarkable improvement of anemia in our patients. But since a measurement of serum ferritin, which provides a simple and reliable method to demonstrate iron repletion or iron overload, became available, it became clear that intravenous iron dextran often resulted in iron overload though we have had no experience of severe organ dysfunction.
We advocated a temporary standard of iron administration.
Our clinical analyses suggest that hemodialysis patients must be always observed carefully in the following ten factors;
(1) quality and quantity of diet (2) G. I. symptoms (3) infection (4) adequate blood access (5) adequate quantity of hemodjalysis (6) blood loss and hemolysis (7) proper supplemental therapies (8) avoidance of heavy blood transfusion and drug-abuse (9) positive attitude to renal transplantation (10) improvement of quality of life.

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Sodium acetate has been used as a substitute for sodium bicarbonate in dialysate solution. However, several reports have suggested that sodium acetate has a depressant action on the cardiovascular system.
In this study, hemodynamic change during five hours hemodialysis was invasively evaluated by a method of left and right heart catheterization in four patients, especially on left ventricular contractility, total peripheral resistance index (TPRI) and their interactions with blood sodium acetate. We adopted max dp/at and max dp/dt/p as indices of the contractility.
At the onset of hypotension with or without untoward symptoms such as yawning, nausea and vomiting, the contractility was depressed with concomittant reductions in cardiac index (C. I.), mean blood pressure (BP) and TPRI. After rapid infusion, the depressed contractility was improved with marked elevations in C. I. and BP. Even during asymptomatic study periods, the contractility might be depressed or enhanuced.
Blood samples for the determination of acetate level were obtained from four sites such as shunt, left ventricle, pulmonary artery and right atrium. The level in shunt was closely identical with those in left ventricle as well as in pulmonary artery. However, in right atrium, it was approximately a half of the level.
Each contractility parameter described above and TPRI were statistically compared with blood acetate levels in all sites. However, no better corelations were found in all. Consequently, it was speculated that cardiovascular depression was unrelated to blood acetate level.

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Heparin free hemodialysis by EVAL (ethylene Vinyl alchol copolymer) H. F dialyzer, we have successfully performed with total of 466 dialysis for patients with hight bleeding risk and regular H. D. patients.
Prior to dialysis, dialyzers were washed out with 1 L heparinized saline (6000u) or 1 L saline containing gabexate mesilate (400mg), and then dialysis was performed without anticoagulant for patients during H. D. Our laboratory studies have shown that these H. D. do not cause any problem in comparison with ordinary H. D..
This is considered to be due to blood compatibility of EVAL itself and antithrombogenenicity arising from surface heterogeneity of unique microporous inner structure of EVAL.

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As a long survival of the patients on chronic hemodialysis has become possible for the establishment of hemodialytic therapy, we began to face the problem of various new complications.
The study was carried out on irregular isoantibodies found in the patients on chronic hemodialysis.
For the screening of irregular isoantibodies, the saline method, the albumin method, the antiglobulin method and the bromelin method were used in combination, in the patients before and every 3 to 6 months after the induction of hemodialysis.
Furthermore, the identification test was performed in the patients who had shown positive results on the screening.
As a result, irregular isoantibodies were found in 2 patients who had had neither blood transfusion nor clinical symptoms.
The first patient had anti-HI antibody and the titer was twice the normal range.
The blood group of this patient was A₁, Rh₁rh₁ (CcDee), NNss, Le(a+b-), P₂, and the direct antiglobulin test was negative. Moreover, cold hemoagglutinin titer using Type O adult human red cells was 32 times as high as normal.
From these results, it was concluded that the irregular isoantibody observed in this patient was cold hemoagglutinin having the specificity to HI substances.
The second patient had anti-P₁ antibody, which titer was twice the normal. This patient's blood group was A₁, Rh₁Rh₁ (CCDee), MMss, Le(a-b-), P₂, and the direct antiglobulin test was negative.
The case reports in regard to the irregular isoantibody in the patientson chronic hemodialysis have been extremely rare in Japan to our knowledge. However, our study showed that the incidence of irregular isoantidodies observed in the patients on chronic hemadialysis was much higher than those found in the multiparae in whom irregular isoantibodies were used to consider most frequent in occurrence. It is easily anticipated that the existance of irregular isoantibodies in the patients on chronic hemodialysis is the extremely important clinical significance, because of their high liability to blood transfusion, surgical operations and future kidney transplantation.
Our study suggests strongly the necessity of routine screening test for irregular isoantibodies in the patients on chronic hemodialysis.

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Subtotal parathyroidectomy (PTX) was performed to seven patients with uncontrollable renal osteodytrophy. We decided the indications of PTX as follows,
(1) Severe bone resorption in radiographic findings,
(2) Persistent high A/-P,
(3) High C-PTH level,
(4) Non effectiveness to the treatment of active Vitamine D.
Preoperative clinical symptoms such as bone and joint pain were observed in all the patients, general itching in 4 patients and muscle weakness in 3 patients, but peptic ulcer and psychic disturbance in no patients. These subjective symptoms showed remarkable remission after the surgery.
The rentogenological changes improved in 5 patients and serum Alkaline-phoshatase normalized in 4 patients 8 months after PTX. No patients showed elevation of serum C-PTH even almost one year after operation.

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Severe transient leukopenia in patients undergoing dialysis (HD) with cellulosic membrane (Cell) and, in contrast to it, very mild leukopenia with poly (methyl methacrylate) membrane (PMMA) have often been reported. On the other hand, decrease in complaints on HD-related symptoms from patients has been suggested on transfer from HD with Cell to that with PMMA.
In order to clarify the probable correlation between biocompatibility of membranes and clinical conditions of patients, following three evaluations were carried out.
1) Seven patients were pairwisely dialyzed with PMMA and Cell, and the hemograms during these treatments were observed.
2) Complement activation especially through the alternative pathway was measured on serum incubated with PMMA and Cell by immunoelectrophoresis.
3) Clinical parameters routinely measured in 19 patients who were switched from HD with Cell to that with PMMA were analyzed and statistical significance of their change was tested.
As already reported, significant difference (P<0.01) was observed on the extent of leukopenia between PMMA and Cell at 15min. from the beginning of HD. In addition, as to the subpopulation of neutrophil, significantly greater left shift (P<0.05) was observed in HD with Cell at 30min. from its start than that with PMMA. In the latter half of HD with Cell, total count of metamyelocyte and stab neutrophil remarkably increased, which might mean the release of immature neutrophils from bone-marrow.
Distinct activation of complement C3 was demonstrated with Cell but scarcely with PMMA.
Among clinical parameters in 19 patients who were switched from HD with Cell to that with PMMA, significant and interesting decrease in pre- and post-HD body weight was detected.
Our observations thus consisted with proposed correlation between leukopenia and complement activation.
It is not easy to pinpoint the true cause of this decrease in body weight accompanied with change of membranes, but it can be hypothesized that complement activation is correlated with drop in body weight through HD-related symptoms and patient tolerance. This hypothesis will be studied in more details.

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The effect of hemodialysis on the immune response, mainly on the peripheral blood lymphocyte subpopulation, was studied. Ten (10) patients on maintenance hemodialysis using cuprophan membrane and 2 patients using polycarbonate membrane had been subjected to our study and lymphocyte subpopulations had been made according to Yata's mixed rosette method. The blood was withdrawn from the patients at intervals of 15, 60 and 120 minutes in addition to predialysis. Results are as follows: 1) Percentages of subsets of double-RFC (Tγ cells: suppressor T cells and a part of killer cells) and EA-RFC (B cells and K cells) decreased markedly in the peripheral blood within 15 minutes after starting of hemodialysis and thereafter returned to former figures after 60 minutes (P<0.001). 2) There was no significant alteration of T cell count percentage in the periferal blood. 3) There was about 20% decrease of lymphocytes in number during dialysis, which was considered to be attributed mainly to decreased numbers of double-RFC and EA-RFC. 4) A mechanism which might have affected those subsets through Fc receptors of IgG was appeared to be one of possible causes of the subsets decrease. 5) Decrease of the neutrophils was not solely attributed to complement activation mechanism. The other mechanism was suggested to be responsible for the phenomenon.

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