A depressor effect of recombinant human erythropoietin (EPO) has been noted in some anemic patients with chronic renal failure undergoing maintenance hemodialysis. In order to clarify the mechanism of the depressor effect of EPO, changes in blood pressure, cardiac function and plasma vasoactive substances were evaluated at, before and after EPO therapy. Twenty-eight dialysed patients with renal anemia (hematocrit value≤23.5%) were treated with EPO to maintain a hematocrit value between 25 and 30%. Before and after EPO administration for 12 months, blood pressure, heart rate, body weight, blood count, echocardiography, plasma adrenaline (pNA), plasma renin activity (PRA), angiotensin II (A-II) and atrial natriuretic peptide (ANP) were determined. Significant depressor effects of EPO were found in 4 patients (DP group) but not in the other 24 (non-DP group). There were no differences in the severity of anemia between these two groups over the 12 month period. Heart rate and body weight were not changed by EPO in either group. Left atrial dimension and left ventricular dimension did not differ between the DP and non-DP groups. Before EPO administration, the left ventriculer ejection fraction was higher in the DP than in the non-DP group. Left ventricular stroke volume (SV) and cardiac output (CO) showed significant decreases or a tendency to decrease with EPO administration, especially in the DP group. As a result, significant positive correlations were found between changes in blood pressure and SV, and blood pressure and CO only in the DP group. No significant difference was found in total peripheral resistance between the DP and non-DP groups. There were no differences in pNA, PRA, A-II and ANP between the two groups.
In conclusion, correction of the high cardiac output state may be one of the mechanisms mediating the deprssor effect of EPO.

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We experienced 27 cases of renal cell carcinoma (RCC), among 1, 352 long-term dialysis patients during the period from April 1984 to January 1992. The incidence was very high, about one in 50 patients (2.0%), 29 times the rate of the control group. We carried out clinical and pathological studies on the RCC of these 27 cases and classified the 261 dialysis patients selected for the study into an HD group and a CAPD group, as well as an ACDK group and a non-ACDK group, carrying out a comparative study in terms of average age, dialysis period, original disease, etc.
As the RCC and cysts generated in chronic dialysis patients showed characteristic histopathological findings, had ACDK which carries a high risk of RCC, and because ACDK occurred regardless of the method of dialysis and was also found in patients before dialysis treatment, the results of this study suggest that pre-existing chronic renal failure is an important factor in the generation of cysts. If at least one cyst is confirmed in the kidney of a chronic dialysis patient, this is a risk factor for malignant transformation and we deem it necessary to closely observe its development.

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Fluorescein angiography is one of the most important tools in diagnosing retinal-choroidal diseases, and sodium fluorescein (NaFI) is widely used as a contrast medium. In the present study, we examined the pharmacokinetics of NaFI in patients undergoing hemodialysis (HD). NaFI, 500mg, was injected into 4 HD patients with ophthalmological complications, and HD was started immediately after fluorescein angiography had been completed. Changes in plasma concentrations and clearance of NafI were studied using a spectrophotometer, and the following results were obtained. Four hours after initiating HD treatment, the plasma concentration of NaFI had decreased to 17.5% of the initial concentration. The in-vivo clearance of NaFI during HD was 35.51±13.90ml/min (Mean±SD). The half life of NaFI in HD patients on a day without dialysis was extremely prolonged compared to those in non-dialyzed patients. Because of these results, together with the relatively good dialysability of NaFI, immediate HD after fluorescent angiography should be considered for the removal of residual contrast medium.

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In order to determine the value of leukocyte counts in peripheral blood (WBC), the erythrocyte sedimentation rate (ESR), and the concentration of serum C-reactive protein (CRP) as markers of acute inflammatory disorders among patients on chronic hemodialysis, changes in these parameters were analyzed in 213 patients.
No significant difference was noted in WBC between patients with and without acute inflammation. ESR was elevated even when no acute inflammation was present, and was even more eleveted when the patients developed various acute inflammatory disorders. CRP was found to be slightly elevated even in the absence of acute inflammation. It did, however, increase significantly with the progression of such diseases. In the absence of acute inflammation, CRP values showed no significant difference among groups of patients with various underlying renal diseases such as chronic glomerulonephritis, diabetic nephropathy, and so on.
CRP values were not significantly different before and after hemodialysis, and the duration of hemodialysis exerted no discernible influence on CRP values. CRP values were slightly higher among patients who underwent hemodialysis with a cuprophane membrane than in those with a PMMA membrane. However, such differences were minimal, and did not appear to conceal the presence of acute inflammation. It was also noted that even in the absence of acute inflammation, CRP values were significantly elevated in 0.6% of the patients investigated, and that CRP values were significantly elevated in all patients in the early stages of acute inflammation. Based on the aforementioned observations, it is concluded that CRP is superior to ESR as an indicator of acute inflammatory disorders, even though CRP values differed slightly depending on the type of dialysis membrane, and that WBC is not a reliable indicator of such disorders.

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Ten patients (7 males and 3 females) undergoing dialysis for polycystic kidney (PCK), in which it is considered almost impossible for immunity to participate as a background factor in the onset of chronic renal insufficiency, and 42 dialysis patients (31 males and 11 females) whose underlying disease was chronic glomerular nephritis, were divided into a short-term dialysis group (less than 2 years; 24 patients) and a long-term dialysis group (9 years or more; 18 patients). T lymphocyte subpopulations, lymphocyte transformation response (PHA, Con A, PWM reaction), NK activity and IL-2 productivity were investigated in these groups.
1) With regard to the T lymphocyte subpopulations, the rates of OKT3- and OKT4-positive cells were significantly (p<0.05) higher in the group undergoing dialysis for PCK (HD_P) than in healthy subjects. 2) All groups showed favorable lymphocyte transformation. 3) NK activity was significantly (p<0.01) lower in the short- and long-term chronic nephritis dialysis groups (HD_S, HD_L) than in healthy subjects. On the other hand, NK activity was within normal range in the HD_P group. IL-2 productivity was normal in all groups.
The above results suggest that immunological competence in HD_P is different from that in dialysis patients with other underlying diseases. It appears to be important to investigate the condition of immunological competence early in dialysis (0-2 years after onset) and to examine annual changes in immunological competence in individual patients with HD_P.

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The clinical and pathological pictures of synovitis in 15 patients (8 male, 7 female) on long-term hemodialysis were studied. The average age of the patients was 54±7 years and the average period of hemodialysis was 12±3 years. They developed swelling, redness, and pain in the region of the bursa around the large joints: the hip (four patients), ankle (three), hand (three), elbow (three), and shoulder (one). The dialated bursae could be distinguished by CT and MRI findings. Eleven patients had carpal tunnel syndrome, for which a carpal tunnel release operation was done, four had bone cysts, and three had tumorous calcification. The infiltration of inflammatory cells, fibrous thickening, and β₂-MG amyloid fibrils were recognized in the synovial tissues. In some cases with bone cysts, both adhesions of the synovial capsule with periosteum and bone necrosis were recognized. Fluid taken from the bursae was yellow, rather than turbid synovial fluid, and showed calcium crystals in some cases. Ultrastructurally, amyloid fibrils and free synovial cells were recognized in the synovial fluid. Culture of the fluid was negative. Based on the presence of β₂-MG amyloid in synovial tissues of the bursa, this bursitis in dialysis patients is considered to be a dialysis-associated amyloidosis. The results of this report suggest that dialysis bursitis is related to bone cysts and tumorous calcification. We must, therefore, include bursitis as a possible diagnosis in patients complaining of arthralgia duruing long-term hemodialysis.

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The pharmacokinetics of terazosin were studied in 10 patients on chronic hemodialysis. Six of the 10 were given single doses of 0.5mg terazosin orally on dialysis and non-dialysis days. The remaining 4 were given 1mg twice daily orally, for 28 days.
The maximal plasma concentration (Cmax) was 14.2ng/ml and the elimination half life in the beta-phase (t1/2) was 12.7 hours in the case of single administrations. There was no apparent difference in the pharmacokinetics of terazosin between dialysis and non-dialysis days. The dialyzability of terazosin was so low that no terazosin was detected in the dialysate.
Plasma levels of terazosin after repeated administration showed no significant difference over the course of the study. The minimal plasma level ranged from 16.0 to 19.4ng/ml and the maximal plasma level ranged from 23.2 to 30.6ng/ml. No accumulation of plasma terazosin was observed in patients on hemodialysis.
These results suggest that terazosin may be safely administered to patients on chronic hemodialysis without altering the usual dosage regimen.

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Areas of cardiac shadow on routine chest X-ray films were measured in 54 chronic hemodialysis patients and two-dimensional cardiothoracic rations, (2°CTRS) defined as the square root of the cardiac shadow divided by the maximal thoracic width, were calculated.
The patients were divided into 2 groups: patients in the A group (22 cases) had dry weights which had apparently been set at high levels, while patients in the B group (32 cases) constituted all of those excluded from the A group.
The mean 2°CTR level in the A group (49.3±3.92%) was significantly (p<0.0001) higher than that in the B group (44.2±3.63%).
The ratio (95.5%) of the A group patients whose 2°CTR level was abnormally high, was significantly (p<0.0001) higher than that (86.4%) of the A group patients whose cardio-thoracic rate (CTR) was abnormally high, suggesting that 2°CTR is more useful than CTR for estimating dry weight (DW).

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We reported previously that the ultrasonographically determined diameter of the inferior vena cava (IVC) changes in parallel with the amount of body fluid during hemodialysis (HD). Since right-side cardiac overload could alter this correlation, we studied the IVC diameter in a uremic patient with atrial septal defect (ASD) (39-year-old woman, NYHA III, CTR=67%, pulmonary arterial pressure=44/16mmHg, pulmonary/systemic blood flow=2.75) before and after surgical closure of the defect.
In the preoperative period, the basic pattern of the change in IVC diameter during HD was maintained, i.e., the maximal diameter during quiet expiration (IVCe) and the minimal diameter during quiet inspiration (IVCi) were decreased while the collapsibility index (CI: 1-IVCi/IVCe) was increased by fluid removal. However, the decrease in IVCe in response to fluid removal was slow and small compared to that in control HD patients. Nevertheless, the correlation between IVCe and circulating blood volume (CBV) was significant (r=0.97, p=0.0001, n=11), and that between IVCe and body weight (BW) (r=0.83, p=0.01, n=8) was superior to that between CTR and BW (r=0.64, p=NS, n=8). These data suggest that IVCe reflects the amount of body fluid even in the presence of right-side cardiac overload.
Comparing pre- and postoperative period, IVCe was smaller at the same CBV, and the decrease in IVCe by fluid removal was significantly enhanced in postoperative period. These suggested that pressure overload imposed by ASD considerably affects the IVC configuration in addition to the systemic volume overload.

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The number of kidney transplantation cases has gradually been increasing in Japan. Along with the growth in the number of transplantation patients, the management and instruction provided for these patients by their dialysis facilities have also become increasingly important. Therefore, we studied ways for patients to cope with transplantation problems in a satellite facility. We instructed patients who were on dialysis in this hospital and who wished to undergo kidney transplantation by dividing the preparation time frame into three periods. I. Learning period: Patients were educated about the differences between dialysis and kidney transplantation and social and medical characteristics of transplantation, according to the patients' comprehension level. II. Preparation period: HLA tests and recipient registration were completed for those who desired to have living or cadaver kidney transplantation. At the same time, we conducted case studies with the assistance of those who had experienced transplantation in the past, in order to help the prospective recipients cope with the expectations and anxiety of the transplantation. III. Transplantation waiting period: We treated and instructed the patients on methods of preventing possible complications that disturb transplantation, such as anemia, and secondary hyperparathyroidism. In conclusion, by means of proper instruction and management we were able to enhance the understanding of patients who wish to have kidney transplantation. We consider it necessary to continue to provide prospective patients with adequate and effective education on transplantation.

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We assessed whether increased RBC counts in patients with renal anemia, in response to erythropoietin (EPO) therapy, can be predicted on the basis in reticulocyte (RET) counts before and after the treatment.
The subjects consisted of 10 stable hemodialysis (HD) patients who had been on HD for 2 years or more and 8 patients who were in the initial stage of HD.
We devised a simulation curve of RBC counts based on the results of serial RBC counts and RET counts before and after EPO administration and various published reports, and derived a formula for predicting increases in RET counts 2 weeks later, i.e. during the period from 4 to 14 weeks after EPO administration.
When we applied the RET and RBC counts at 4 weeks after EPO administration to this prediction formula in six of the stable HD patients and compared predicted values with the actual values at 8 weeks, they proved to be very similar, suggesting that it was possible to make the predictions.
When the actual values for RBC counts and RET counts were compared with the predicted values in the initial stage HD patients, the actual values were somewhat higher than the predicted values.
The average increase in the RBC count 5 weeks after EPO administration was 460, 000 in the stable and 820, 000 in the initial stage HD patients. The latter value was approximately 1.8 times higher than that of the stable HD patients.

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To evaluate the biocompatibility of hemodialysis membranes, twenty patients (10 male, 10 female) on maintenance hemodialysis were treated with different dialysis membranes, and the plasma levels of the generated terminal complement complex (TCC) were compared. Quantitation of TCC was carried out by the sandwich ELISA method using a monoclonal antibody against the neoantigen (by Kusunoki) of TCC.
With cuprophan (Cu), the plasma concentrations of TCC at 30min, 2hrs and 4hrs after the start of dialysis were higher than the corresponding predialysis levels. These concentrations were significantly higher than those obtained with synthetic membranes such as ethylenvinylalcohol (EVAL) and polysulfone (PS) dialysers. No significant difference in TCC concentrations was obtained with EVAL or PS.
ELISA quantitation of plasma TCC proved to be useful for evaluating dialysis membranes.

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A case of acute renal failure associated with nontraumatic rhabdomyolysis of the iliopsoas muscle is reported.
A 57-year-old man was referred to our hospital because of uremia and abnormal blood levels of GOT, GPT, LDH and CPK.
He was treated with hemodialysis for the anuric and oliguric phases of acute renal failure. Two months later, he was discharged in good clinical condition.
On admission, abdominal CT showed that the iliopsoas muscle was the cause of rhabdomyolysis, as indicated by muscle swelling and high density areas in some portions of the muscle. One month later, the muscle had recovered normal size and density.
In this case, abdominal CT was very useful in establishing the cause and prognosis of the disease.

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A 48-year-old woman with ESRD maintained on regular hemodialysis for 8 years presented with various neurologic manifestations including multifocal myoclonus, tetraplegia, speech disturbance, progressive intellectual decline, amnesia, confusion and coma. The initial episode occurred one month after resection of her lung cancer. At the onset, EEG revealed diffuse slow waves, although brain CT scanning showed no pathologic changes other than slight cortical atrophy. The protein level in her cerebrospinal fluid was extremely elevated, and there was a marked albuminocytologic dissociation. Though the serum aluminum concentration was 8.2μg/dl, so-called dialysis encephalopathy due to aluminum accumulation was not likely because the dialysate had been prepared with water by reverse osmosis and no aluminum containing phosphate-binders had been administered. Two months later brain CT scanning revealed diffuse edema of the white matter compatible with progressive multifocal leucoencephalopathy (PML). The definitive evidence for a diagnosis of PML was established by detection of JC virus (a member of the papova virus group) antigen from cerebrospinal cells and anti-JC virus antibody from cerebrospinal fluid at the acme. She was sustained on IVH and had recovered completely five months after the onset.
The prognosis of PML has been reported to be rather poor. Nevertheless, our patient's course was relatively benign, probably due to improvement of immunological defence mechanisms associated with the lung cancer resection. We conclude that it is important to differentiate slow virus infections, such as PML, from other dialysisrelated encephalopathies because of the similarity in their manifestations.

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We report here a patient who developed acute renal failure due to non-traumatic rhabdomyolysis associated with diabetic ketoacidosis. A-67-year-old man withno history of diabetes mellitus was admitted to another hospital because of vomiting, diarrhea and loss of consciousness. On admission, his systolic blood pressure was 50mmHg.
Laboratory data were as follows: glucose 1, 650mg/dl, BUN 78mg/dl, Cr 6.2mg/dl and pH 6.889. Diagnoses of diabetic ketoacidosis and acute renal failure, probably due to hypotension, were made. His condition was well controlled and he subsequently recovered renal function. However, he was transferred to our hospital because of deterioriating renal function. On admission, glucose was 440mg/dl, BUN 204.3mg/dl, Cr 8.9mg/dl, CPK 10, 430IU/l and serum myoglobin 2, 863.5ng/ml, We made a diagnosis of reccurrence of acute renal failure due to non-traumatic rhabdomyolysis. Hemodialysis was started and thereafter renal function recovered. A positive test for anti-islet cell antibody was confirmed. Based on this evidence, we concluded that he had contracted insulitis and consequently developed diabetic ketoacidosis, which caused non-traumatic rhabdomyolysis leading to acute renal failure.

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The increased incidence of malignant tumors in maintenance hemodialysis patients has been pointed out. In particular, urinary tract tumors have been said to be high. We report three cases of bladder cancer in maintenance hemodialysis patients. The cases were all males whose ages were between 56 and 68 years. The duration of dialysis was 2 years to 2 years and 9 months. The first symptom of bladder cancer was gross hematuria in all and two cases had lower abdominal pain as well. Two cases had superficial bladder cancer for which TUR-BT was performed. They are now alive and free of disease recurrence. The other case was advanced bladder cancer with invasion of the prostate and metastasis to sacral bone. Because of severe bleeding, we performed simple cystectomy for control. In this case, preoperative abdominal CT indicated bilateral hydroureter and hydronephrosis suggesting obstructive nephropathy by bladder cancer which contributed to the later development of renal failure. An ureterocutaneostomy was done for recovery of renal function but was unsuccessful and the patient died 80 days after surgery.
Since Matas first reported the high incidence of malignant tumors in hemodialysis patients, a number of similar reports have appeared, especially on urinary tract malignancies.
Ohta reported that the incidences of urinary tract and uterine cancers were high in the inductory phase of hemodialysis. This suggests that these tumors may be a causative factor in obstructed nephropathy leading to renal failure in such patients.

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We report a 45-year-old man with chronic rejection of an allograft seven years after living donor renal transplantation, who had been treated with hemodialysis seven years previously. He was hospitalized because of dyspnea and palpitation. We diagnosed congestive heart failure secondary to chronic renal failure, and performed hemofiltration (HF) several times. After two weeks, he suddenly went into circulatory shock during HF and died soon afterward. Autopsy revealed marked calcification in the aortic valve and gross cardiomegaly (820g). Hyperplasia of the four parathyroid glands (up to 1.5cm in diameter) was noted. It seemed that longstanding renal dysfunction had induced secondary hyperparathyroidism and a metabolic calcium disorder.

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We report a patient who developed myasthenia gravis and underwent double filtration plasmapheresis (DFPP) and immunoadsorption plasmapheresis (IAPP). A 55-year-old woman had palpebral ptosis, muscle weakness of the extremities, easy fatigability and dysphagia. She was diagnosed as having drug resistant myasthenia gravis and DFPP therapy was initiated. Neurological findings improved remarkably with DFPP. However, hypoproteinemia, associated with colonic diverticulitis and respiratory dysfunction, was so severe that we changed from DFPP to IAPP treatment. Although pleural effusion was noted temporarily, she recovered and hemopurification was no longer necessary 8 months after admission. We used Evaflux 3A as a second filter in DFPP and Immusorba TR-350 as a plasma adsorbant in IAPP. Hemopurification was performed 20 times with DFPP and 17 times with IAPP, using 2.5l filtrated plasma. Reduction rates of IgG were 54% in DFPP and 39% in IAPP. Acetylcholine receptor antibodies were reduced by 46% with DFPP and 59% with IAPP. These findings suggest that frequent, long-term DFPP may predispose patients to serious infections secondary to hypoproteinemia and suppression of host defence mechanisms.

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A case of panperitonitis due to rupture of a colon with dialysis amyloidosis of β₂ microglobulin origin (β₂-MG) is reported. A 71 year-old female who had been on hemodialysis for 15 years was hospitalized for acute abdominal pain. A diagnosis of panperitonitis due to ruptured colon was made and a 150cm segment of colon was resected. Amyloid deposition, immunohistochemically identified as β₂-MG, was demonstrated in blood vessels of the submucosal and muscle layers of the colon. Massive deposition of dialysis related amyloid in the muscle layer was considered to have been the cause of colonic rupture in this case.
Possible involvement of intestinal amyloidosis should be considered in every long-term hemodialysis patient undergoing abdominal surgery.

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We report a CAPD patient who showed massive bloody effluent two days after a sudden episode of left back pain. The hemoperitoneum was due to spontaneous renal rupture which was diagnosed by computed tomography and selective angiography. He was managed conservatively with transarterial embolization to the left renal artery, and he maintained his usual peritoneal dialysis progress without loss of peritoneal membrane functions. Massive hemoperitoneum is an unusual complication in patients undergoing CAPD. In most cases, it's due to a benign process such as menstruation or enema and disappears spontaneously in a few days. But the present case and those in the literature indicate that hemoperitoneum in CAPD patients is not always directly related to renal failure or its therapy.

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