The late Professor Nobuo Yasuyama suffered for several years from chronic renal failure caused by urolithiasis. He recovered through hemodiaiysis, which was begun on July 31, 1976, and he continued to receive treatment as an outpatient from September 1 of that year.
Beginning in the middle of March, 1981, however, he would lose consciousness during hemodialysis, although he would recover it afterwards, blood sugar, electrolyte, blood gas, and liver function tests were performed before and after hemodialysis, but with no significant findings as to the cause of his losing consciousness. His EEG showed deep sleep waves or disterbance of consciousness waves.
Professor Yasuyama died on April 4, 1981.
The autopsy showed that the cause of death was edema in the lungs. There were no specific findings to suggest the cause of his losing consciousness. The autopsy also revealed a nonfunctional pancreas tumor composed of non-β cells, but this also appeared to be unrelated to the loss of consciousness, Thus it is still not known why Professor Yasuyama lost consciousness during dialysis.

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Hemodialysis has been recognized to provide effective therapy for patients with chronic renal failure, meantime the increasing number of patients for hemodialysis has, however, raised new problems in economical and social points of view. One of the ways to solve the problems is therapy prior to hemodialysis, for supressing progression of disease and for retarding time to introduce patients into hemodialysis. For this purpose, carbonaceous adsorbent developed for oral use (AST-120) was subjected to clinical study; the results obtained so far were summerized.
Under conservative therapy for chronic renal failure, the adsorbent was administered at doses of 3-12g/day to 42 patients with serum creatinine levels of 4.3-13mg/dl. Clinical courses were followed at least for 6 months or until hemodialysis was introduced. Serum biochemical parameters and periods until hemodialysis were also examined. The results were evaluated in comparison with control data taken from natural history in 37 patients without the adsorbent therapy in the same hospitals.
During continuous treatment for 3-39 months, reduction of the increasing rate of creatinine levels (Cr) was observed in many cases. This was most clearly demonstrated in slope of regression line in 1/Cr vs time plot; the average slope during the adsorbent therapy was found to be much smaller than the slope before the therapy in the same patients and in the control data. Improvement of symptoms and reduction of abnormal peaks in serum analysis by liquid chromatography were also observed in some cases. The average periods from stages of creatinine levels of 6 and 8mg/dl to hemodialysis were 12±2.2, 8.3±0.9 months, respectively, in the patients under the adsorbent therapy. These periods were found to be clearly prolonged over the control data, 5.8±0.8, 2.6±0.5 months, respectively. Side effect attributable to the adsorbent was not experienced so far.
Those results led to the conclusion that the oral adsorbent therapy could retard time to introduce patients into hemodialysis, presumably by removing toxic metabolites such as uremic toxins at least in part. Further study is in progress.

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High sodium dialysate plays a very important role in prevention of hypotension during dialysis and general fatigue after dialvsis, increase in appetite, improvement of anemia, and loss of basal body weight. As plasma osmotic pressure is maintained at higher level in high sodium dialysate, plasma refilling rate from interstitial tissues into capillary is larger than in conventional low sodium dialysate.
Several types of therapy used high sodium difalysate are as follows: dialysis with physiological sodium concentration (less than 150mEq/l) in dialysate, with unphysidogical sodium dialysate concentration (more than 160mEq/l), sodium gradient method (SGM), and cell-wash dialysis (CWD).
In unphysiological high sodium dialysate (UPHSD), clinical findings such as improvement of nitrogen metabolism and large amount of intracellular fluid removal are recognized. At the same time, however, it is difficult to maintain sodium balance. To solve this problem, sodium gradient method (SGM) and cell-wash dialysis (CWD) would be effective.
In a case having been treated with CWD for more than 2 years, clinical results are observed as follows: disappearance of angina attack, decrease of urea appearance and increase in removal amount of potassium.
Therefore, high sodium dialysate would be actively used to cases who have side effects treated with conventional dialysis.

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The use of acetate as an alkalizing agent in the dialysate solution solves the problem of precipitation of calcium and magnecium salts in the bicarbonate containing solution. However, with the development of a high-performance dialyzer, the following adverse effects of acetate dialiysis have become obvious:
1) Acetate overloading on the patients.
2) Pharmachological effect of acetate on the cardiovascular system.
3) Decrease in blood Po₂ induced by the loss of CO₂ through the dialyzer.
4) Inaccurate correction of acid-base balance.
5) Acetate influence on lipid metabolism.
6) Acetate influence on calcium matabolism.
The incidence of hemodialysis related symptoms was significantly reduced in bicarbonate dialysis compared with acetate dialysis.
In order to prevent precipitation of calcium and magnecium salts, pH of the solution should be kept stable by controlling PCO₂. Since the recent development of the device has succeeded in supplying the stable bicarbonate dialysate, bicarbonate dialysis has become a more suitable therapy for the cases of acetate intolerance, cardiovascular complications, severe complications in maintenance hemodialysis, introduction to hemodialysis and short time dialysis with a large surface dialyzer. When acetate dialysis was changed to bicarbonate dialysis, clinical data in those patients showed obvious improvement.

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It is more than 5 years since we introduced hemofiltration (HF) for clinical use in January, 1976. We have investigated this treatment both from the standpoint of hard wares such as filter and HF device, and soft wares such as filter performance and the body response to mass-transfer. With the development in technology, those hard wares can now be clinically used with satisfaction. As for the soft wares, the analysis of filter performance with consideration on the solute-removal in the body has been under investigation. Due to the progress in the soft wares as well as in the hard wares, the range of molecular weight of the substances to be removed by HF, including certain types of protein, has been extended. As the result, the incidence of disequilibrium syndromes and hypotension is significantly reduced and carbohydrate and amino acid metabolism are improved. Therefore, HF is considered a more effective treatment for the chronic renal failure patients.

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Conventional artificial kidney effects its transference of substances based on the diffusion through a membrane and ultrafiltration. Amoung these functions, dialysis plays the major role in the transference of substances. Therefore, most of the substances to be transfered are low moleculare weight and effect depends on the properties of the membrane, especially its thickness and pore size.
Recently attention has been paid particularly to middle moleculare weight substances in uremic toxins and studied on hemopurification technics better than dialysis are progessed in the removal of these substances and the results have come to be applied them to clinical trials. The hemopurification utilizing an adsorbent is one of them. This process utilizes the strong power of substances concentration to remove substances directly from the blood and has, compared with dialysis, advantage of being capable of removing middle moleculare substances and disadvantage of being impossible of adsorption to water and electrolytes.
In the development of adsorption-type artificial kidney, we have made great effort of developing better hemopurificiation as well as dialyzers in order to make the best use of only advantage of dialysis and adsorption. In the present stage here, we would like to mainly describe our clinically applied artificial kidney system by mean of hemopurification utilizing the combination of adsorption and dialysis.
In this series, bead-charcoal originating from petroleum pitch coated with thin cellulose membrane is used as an adsorption material. This carbon was autoclaved and palced in a spindel-shaped cartrige by 130 grams, thus being ready for application. As stated before, activated charcoal can adsorb no water and electrolytes and little urea nitrogen, but these functions are essential in the maintenance dialysis treatment. Thus, the defect is covered by the combination with conventional dialyzer to create a new type of an artificial kidney system. As matter of course, in a few cases where the treatment has been just initiated, some of them requires only little control in water, electrolytes, acid-base balance and are possilly treated by this hemopurification device with oral or intravenous administration of drugs. In these cases, only the adsorption-type hemoperfusion device is employed.
For treatment of chronic renal failure:
1. Shortening of maintenance dialysis.
One of the earnest desires of chronic hemodialysis patients is to shorten the dialysis time. Actually, in the social life, it is hard to say “normal” that pepole are restricted to beds in order to undergo dialysis for 5 to 6 hours. Thus the 3 hour-maintenance dialysis has many advanteges. This new hemopurification system combined with hemoperfusion and hemodialysis could cut off the time of dialysis from 5 or 6 to 3 hours. There is a case treated to 3 hours, 3 times in a week for 3 years with this new method.
2. Reduction of frequency of maintenance dialysis.
This method is possible to reduce dialysis frequency from 3 times to twice a week without changing the time for every dialysis. Even now, 2 years after the start of this trial, they keep well with hemopurification twice a week.
3. Application for an introducing stage of chronic hemodialysis.
The preservation of remaining renal functions by this purification technique also is applicable immediately to the treatment of an introducing stage of chronic hemodialysis treatment. By using this method to new patients, they keep their high urinary out put volume for long time, resulting no increase of dialysis time in a week.
4. Treatment of special cases (uremic pericarditis and neuropathy).
This new process that is thought to effect removal of middle molecular weight substances has very effective for treatment of uremic pericarditis and neuropathy caused by uremic toxins.
For treatment of acute renal failure:
As in the effectiveness in the treatment for chronic renal

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Continuous ambulatory peritoneal dialysis (CAPD) is now accepted world widely as effective dialytic method for chronic renal failure.
In this review, the procedure, characteristics of solutes and fluid removal, complications and management are introduced. Some aspects of metabolic consequences such as glucose, potein and lipid metabolism, calcium, phosphorus, parathyroid hormone, vitamin D and dialytic bone disease are discussed.
Additionaly, the clinical experience of CAPD in Japan are discribed.
In Japan, dialytic system is promptly operated, however, the rehabilitation status is far from satisfaction, because of lower population of kidney transplantation than that of other countries. In this situation, CAPD migt be substitutable for kidney transplantation as anoher advantageous dialytic method for achieving good rehabilitation.

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According to the recent advance in technology of hemodialysis (HD), the survival rate of longterm HD was prolonged. However, there is a number of medical complications during longterm HD and it is not infrequent that some of the dialysis complications induce fatal outcome. The highest mortality among the dialysis patients in this country is heart failure, and the second is cerebrovascular accident. The complications of cardiovascular system of the dialysis patients, were discussed.
(1) Heart failure
It maybe considered that most of the symptoms similar to left-side heart failure are pulmonary congestion due to fluid overload. Diminished cardiac contraction in the real heart failure secondary cardiac disease is not frequently seen in the dialysis patients.
(2) Pericarditis
The pathogenesis of pericarditis is not simple but it is considered that uremic multiple serositis may participate.
(3) Abnormality of blood pressure
Abnormality of blood pressure regulation, either hypertension or hypotension, may be due to change of regulatory mechanism of the central and peripheral circulation, mainly resulting from the factors such as fluid overload, peripheral vascular resistance, humoral and neurogenic control, etc.
(4) Arrhythmia
Pathogenesis causing arrhythmia may be related to abnormal electrolytes, anemia, cardiac load due to ultrafiltration during HD, uremic cardiomyopathy, and effect of drugs like cardiac glycosides.

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In the developement of renal anemia, the deficiency of erythropoietin and the presence of toxic substances to supress bone marrow are two major pathogentic factors. In the case of hemodialysis patients, iron deficiency due to intradialyzer residual blood and hemolysis due to exogenous toxins must be considered.
The principle of treatment is to eliminate the two major factors. Although erythropoietin supplement is not available today, the androgens can stimulate erythropoietin secretion and also act directly on bone marrow to stimulate eythropoiesis. To eliminate toxins of middle molecular weight, hemofiltration and peritoneal dialysis are effective. We described the experiences about the effect of mepitiostane, the androgen derivative newly developed in Japan, and as well the effect of long term hemofiltration. Mepitiostane is very effective to raise hematocrit and causes liver dysfunction rarely. The combination of the drug and hemofiltration is expected to be more effective.

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Several endocrinologic abnormalities have been described in patients with chronic renal failure. In this paper we report sexual dysfuction in male patients on chronic hemodialysis.
1) The investigation of sexual activity through questionnaires performed 4 times during 1968 to 1981 shows that 36.9% of the patients have no interest in sexual activity, 72.9% complain of diminished libido after the onset of dialysis therapy, and 28.4% enjoy sexual life. The loss of libido results from impotence in 32% of the patients, and reduced potency such as an inability to maintain erection or inadequate penile tumescence in 67%.
2) The histological chages of testis consist of atrophy and hyalinosis of the seminiferous tubules, thickened tubular basement membranes, severe hypospermatogenesis hyperplasia of interstitial connective tissues, and apparent hyperplasia of Leydig cell. These findings are regarded as the partial changes to be seen in the chronic wasting diseases rather those of renal failure.
3) As the period of the conservative therapy before hemodialysis is longer, azo-or oligospermia to be severer. Though the once acquired changes seem to be irreversible, the acceleration can be prevented by the adequate dialysis therapy together with high protein diet, and the fertility may be preserved longer. Therefore, an early initiation of hemodialysis is recommended in the young mal patients with renal failure.
4) Serum levels of prolactin are elevated, and LH and testosterone are reduced. When compared with patients with normal prolactin level (group A: 23.7±7.34mIU/ml), the hyperprolactinemic patients (group B: 91.6±24.5mIU/ml) show significantly higher serum level of LH (A: 10.1±4.0, B: 64.1±29.8mIU/ml), and lower level of testosterone (A: 286±86, B: 227±87ng/dl). But the serum levels of FSH, GH, 17β-estradiol and cortisol are not significantly different between the two groups. Hyporesponsiveness in TRH test and abnormal pattern in clomiphene test suggest the hypothalamic-pituitary axis dysfunction as well as atrophy of testis.
5) Endocrinologic abnormalitites reflecting in hyperprolatinemia, lower serum levels of LH, testosterone, along with the psychological and nutritional factors play the major role in the pathogenesis of the sexual dysfunction commonly recognized in chronic hemodialysis patients. It is aiso suggested that lowering prolactin with bromocriptine or ZnSO₄ may restore the gonadal function to normal.

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Abnormal metabolism of carbohydrate in chronic renal faliure is one of the most important problems on clinical practice, for the investigation of the lesion will develop the prognosis of dialysis patients. Abnormal metabolism of carbohydrate in chronic renal failure is called uremic psedodiabetes and is analogous to the behavior of chemical diabetes. This lesion is generally improved by dialysis.
On the other hand, insulin level in chronic renal failure is raised but we didn't find always a certain result on insulin response to glucose. Glucagon level is raised and besides glucagon response activity to protein meal. Regarding to growth hormone, its level is raised by renal failure because of deteroration of dissolution and abnormal secretory of itself. The behavior of C-peptide by loading arginine is not the same to that of insulin, which may be thought to be related to difference of hormone clearance in kidney. Hemoglobin A₁ is increased by chronic renal failure, which cannot be said by abnormal metabolism of carbohydrte of renal failure, but is mainly due to the lesion of renal failure such as acidosis.

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Progressive advances in dialysis treatment have altered clinical manifestations of renal failure. This has been particularly striking in the area of neurology, resulting in the definition of new syndromes as a consequence of both increased longevity and the complications of dialysis treatment.
The current situation is reviewed and the results of a study of neurological complications in renal failure are described.
Full-fledged clinical uremic encephalopathy and neuropathy have become scarce but they are often experienced subclinically. About 50% of dialysis outpatients have indicated subnormal and predementia patterns in electroencephalograms. Postmortem neuropathological studies of dialysis patients indicated a decrease in brain edema but an increase in brain atrophy, micro-softening, microbleeding, degeneration, and demyelination such as central pontine myelinolysis with prolonged dialysis. Many factors, for example, abnormal metabolism, renal failure, abnormal cerebral circulation, trace elements, various deficiencies and so on are attributed to cerebral dysfunction.
Death due to cerebro-vascular disease is increasing annually among long-term dialysis patients. It is necessary to prevent accelerated atherosclerosis and maintain cerebral circulation through control of optimum blood pressure.
Subdural hematoma in a well-defined complication which CT scanning easily confirms. Today, the disequilibrium syndrome in more often observed in treatment involving the use of high dialysance dialyzers. However, hemofiltration is available for the prevention of the disequilibrium syndrome. The accumulation in the body of trace elements in the dialysate permeating the dialysis membrane is a major problem. Aluminium poisoning especially is reported as one of the main causes of dialysis encephalopathy, but hyperparathyroidism and phosphate depletion also are reported to be responsible. The appearance of any new neurological symptom in a dialysis patient calls for a review of all drug terapy. Both dialysis therapy and rehabilitation are necessary for patients with atrophy of disuse and dementia.
Generally, neurological symptoms are slowly progress and therefore may be overlooked. Accurate observations of neurological symptoms and neurological examinations may uncover answers regarding pathogenesis and therapy in neurological complications.

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In proportion to a rapid increase of dialysis patients, a sabstantial number of the patients have undergone operations from variety of surgical diseases. However, in dialysis patients, there are many problems such as metabolic, coagulatory, circulatory disorders which make it difficult to perform surgery.
In this report, abnormalities observed in dialysis patients are described along with their influence during surgery and post operative period, in addition to statistical analysis of the patients and the incidence of cancer among dialysis patients.

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The development of antimicrobial agents has been remarkable for these ten years.
Especially, in penicillins, cephems, and aminoglycosides, antimicroial activities of new agents have been evidently intensified. On the other hand, nephrotoxicity of cephems and aminoglycosides and ototoxicity of aminoglycosides have been decreased.
The new antimicrobial agents are useful for the treatment of infectious diseases of patients with renal dysfunction similar to those of patients with normal renal function.
In uremic patients, pharmacokinetics vary according to the degrees of their renal damages. Therefore, it might be carefully studied to select the antimicrobial agent and to decide its dosage when we treat the infectious diseases of uremic patients.

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Sixteen cases with an initial diagnosis of hypoplastic or small kidney detected by IVP, VCG, Echogram, RI scan, CT scan or Angiography were studied. We investigated to find out what common factors affect their growth, the rate of change of creatinine concentration, and to find out possible effects of medical therapy.
Height and weight were graphed, which were well correlated with linear regression of the serum creatinine versus time. Analysis of these relation gave an estimation of progression of disease, the possible effects of therapy and to predict when dialysis will become necessary. The commonest reason for discovery were firstly due to episodes of urinary tract infection and secondary by routine school check ups for urinalysis (5/16) Of the 16 patients that were found to have a small kidney, 10 was finally diagnosed to have hypolastic kidney, 5 were bilateral, 5 were unilateral. Of the-patients that were found to have an atrophic kidney secondary to pyelonephritis, 3 of them were associated with bilateral VUR, one was associated with unileteral VUR. Impairment of renal function was observed in those who have bilateral renal anomaly with VUR, or who have unilateral UPJ obstruction and agenesis of another kidney.
The important roles of the pediatrician in prevention of chronic renal failure among those children are early recognition of the urinary tract infections which damage the renal function in them. Screening of proteinuria, hematuria and hypertension in asymptomatic children with renal anomaly is also useful in early detection in them, and is essential for the prevention of the development of chronic renal failure.

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Until December 31, 1980, 1, 700 renal transplants including 1, 461 living related grafts were performed in Japan. The overall patient and graft survival of the related transplants at 5 years were 67.3% and 46.5%. Since 1971, both patient and graft survival have been improving and recent 3-year patient survival was about 15% higher than that of patients on hemodialysis.
In related transplants, graft survival is strongly influenced with the shared haplotypes by donors and recipients. Namely, while the survival of the grafts from 2-haplotype identical sibling can be expected about 90% at 5 years; that of 1-haplotype identical grafts is about 50%. The survival rate of the latter is not satisfactory for the donation from living relatives.
In 1980, the beneficial effects of HLA-DR matching and pretransplant blood transfusions on cadaver transplants was confirmed in the International Histocompatibility Workshop Study on Renal Transplantation. However, because of small number of related donor transplants, this analysis was limited to grafts from cadaver donors.
Ninety seven living related transplants performed at The Institute of Medical Science Hospital, The University of Tokyo were analyzed on the effects of HLA-D matching, HLA-DR matching and pretransplant blood transfusions. Actuarial survival rate of the HLA-D compatible grafts at 5 years was 85.5% and that of the HLA-D incompatible grafts was 46.5%, resulting in a significant difference (P<0.05).
The correlation between HLA-DR matching and graft survival was examined in donor-recipient combinations excluding 2-haplotype identical siblings. One-year survival of the 2-DR antigen-matched grafts was 81.8%; that of the 1-DR antigen-mismatched grafts was 72.4%. There was no statistical significace.
Among 1-DR antigen-mismatched grafts, 50.0% of the recipients preoperatively transfused with less than 1000ml blood lost their graft function within 1 year. The graft survival rate (50.0%) was significantly lower (P<0.01) than in recipients preopreatively transfused with more than 1200ml blood (93.3%). From these results, it might be possible that pretransplant blood transfusions improve the survival of the 1-DR antigen-mismatched grafts up to the level of that in 2-haplotype identical siblings.
Besides random transfusions, donor-specific blood transfusions in related transplants have been initiated at some centers. Recent reports of Salvatierra and ours indicated that the administration of 200ml of donor blood on 3 separate occasions at 2-week intervals proved to be effective for a purpose of improving the survival of the related kidney grafts without producing cytotoxic antibodies against the donors.

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It is about 15 years since the first clinical cadaveric renal allograft succeeded in our country. The total number of patients with renal allografts alive on 31st December 1980 is 1700, of whom 868 has a functioning transplant, and 239 are transplanted with cadaveric kidney. This represents a mean figure 2 cadaveric grafts per million population per fifteen years in Japan, while a mean European rate of transplantation is 6 grafts per million popuration per year.
Cadaveric renal transplantation has become the treatment of choice of endstage renal failure, primarily because of the marked improvement in patient survival, as well as in graft survival.
The role of matching for HLA in cadaveric kidney transplantation becomes the far greater importance. There is resonable agreement in Japan that cadaver kidneys well matched for HLA will show better survival than poorly matched. The National Kidney Center Registry has a file of 2000 potential transplantation recipients sorted by HLA type. Using the match program, cadaveric renal transplantation carry out by this listing of the HLA B, C matched patients, and detailes such as antibody status, blood transfusions, and age.
Health and Welfare Ministry achieves a cadaveric renal transplant shared imformation computer system which has a main computer and a data base in National Kidney Center connected with subcenters' terminals on line.
Blood transfusions before transplantation improve cadaveric graft survival although the mechanisms are unclear. The ultimate goal of transplantation is the induction of specific unresponsiveness to an allograft. This may be achieved by antigen pretreatment of the recipient before transplantation.
There is increasing evidence that immunological unresponsiveness can be induced by either suppressor T cells or antibodies directed against the T cell receptor, that is, anti-idiotypic antibodies. We can expect that the long survival of the renal graft may be due to an immunological unresponsiveness induced by the host immunoregulartory mechanism of transplant patient.

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