We investigated the pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with renal failure who were undergoing hemofiltration and in a in vitro model of hemofiltration. The filters employed for hemofiltration were the PAN-50P filter and BK-1.0 filter. The conditions for hemofiltration were a blood flow rate of 100ml/min and a fluid replacement value of 1, 200ml/hr in vivo or 180ml/hr in vitro. The concentrations of cefotaxime and desacetylcefotaxime in serum and filtrate were determined by the HPLC method.
In the in vitro model of hemofiltration, the half-lives of cefotaxime were 1.78hr on hemofiltration using the PAN-50P filter and 1.53hr on hemofiltration using the BK-1.0 filter. The transfer rates omission hemofiltration using the PAN-50P and 90.9% on hemofiltration using the BK-1.0 filter. In the case of fluid replacement at 1, 200ml/hr in hemofiltration using the PAN-50P filter, the serum cefotaxime concentrations at 5 min and 5hr after cefotaxime administration were 145μg/ml and 14.4μg/ml, and the half-life was 1.80hr. The mean serum concentration of desacetylcefotaxime reached 12.8μg/ml at 4hr. In the case of fluid replacement at 1, 200ml/hr in hemofiltration using the BK-1.0 filter, the serum cefotaxime concentrations at 5 min and 5hr after cefotaxime administration were 150μg/ml and 6.0μg/ml, and the half-life was 1.26hr. The mean serum concentration of desacetylcefotaxime reached 14.7μg/ml at 4hr. It was concluded that part of the cefotaxime was bound to the protein filtered on hemofiltmation using the BK-1.0 filter, and desacetylcefotaxime was bound to the large molecular protein which was not filtered on hemofiltration using the BK-1.0 filter.

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Creatinine (Cr) is the end product of guanidinoacetic acid (GAA) -creatine metabolism, an essential energy source for muscle and nerve tissue. GAA is produced mainly by the kidney. Previously, we reported that the serum concentration and urinary excretion of GAA were decreased in patients with chronic renal failure, especially in diabetic nephropathy.
In this study, we evaluated the urinary excretion of Cr (U-Cr) during the progression of renal failure in 48 noninsulin dependent diabetic patients. Hemodialysis therapy was required for only about 2 years from the early stage of renal impairment (serum Cr=2mg/dl). In this study, body weight (BW) and U-Cr were significantly decreased (57.3±10.6→51.0±11.2kg and 664±208→551±201mg/day). U-Cr of diabetic patients was also significantly lower than that (739±311mg/day) of patients with chronic glomerulonephritis (CGN) at the initiation of hemodialysis therapy. U-Cr/BW of diabetic patients (10.8mg/kg) was significantly lower than that of CGN patients (14.0mg/kg).
These data showed that the lean body mass rapidly decreased in the short course of renal failure and suggested that the deterioration of GAA production in addition to lean body mass might cause the decrease in urinary Cr excretion in diabetic patients.

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To study the mechanism of the degree of long-term ultrafiltration (UF) per dialysis to the progression of left ventricular hypertrophy (LVH) on regular hemodialysis (HD) therapy, M-mode echocardiography was performed at an average of 6 months after the start of HD and repeated at intervals of 1 year for two years. At the time of the third UCG, humoral factors such as plasma norepinephrine (PNE), plasma renin activity (PRA) and parathyroid hormone (PTH) were also measured before and after HD to clarify the mechanism of LVH progression.
Nineteen patients were divided into 3 groups by the degree of UF, which was unchanged in each patient during the period of observation. Patients with valvular disease, myocardial infarction and diabetes, and those undergoing administration of antihypertensive agents, were excluded from the study. Nine patients comprised Group 1 (UF<1kg), 6 Group 2 (1≤UF<2kg) and 4 Group 3 (2kg≤UF). The ultrafiltration rate (UF/dry weight) was higher in Group 3 (4.50±0.41%) than in Groups 1 (1.44±0.47%) and 2 (2.80±0.19%).
Between the first and third UCG, left ventricular mass (LVM) decreased significantly in Group 1, showed no significant change in Group 2 and increased significantly in Group 3.
At the time of the third UCG, PNE and UF were significantly higher in the LVH group (LVM≥200g) than in the non-LVH group (LVM<200g): PNE (609±359 vs 253±151pg/ml) and UF (1.66±0.57 vs 0.90±0.41kg). On the other hand, there were no differences in MBP, hematocrit, PRA and PTH between the 2 groups. LVM and FS tended to correlate with PNE. In terms of the relation between the degree of OF and humoral factors, PNE was significantly higher in Group 3 (785±349pg/ml) than in Groups 1 (277±160pg/ml) and 2 (339±257pg/ml). PRA in Group 3 was lower than that in Group 2. PNE and PRA increased sighificantly after HD in Group 2, but not in Group 3. In terms of PTH, no differences were found befween the 3 groups.
These results suggest that high PNE may contribute to the progression of LVH in patients with long-term, excessive UF. It is also suggested that a level of UF under 2kg per dialysis, that is, less than a 3% ultrafiltration rate, is important in preventing the progression of LVH.

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Diets for hemodialysis patients should be high in the quality and quantity of protein. When protein is taken in, however, much phosphate is also consumed. As a result, it is difficult to maintain a low serum phosphate level.
To solve this problem, we developed low phosphorus “tofu” (FP16) and high-protein bread (BP) using high-protein, low-phosphorus powder. We also devised several foods to eat with them, and determined whether or not these foods can be eaten daily.
Our newly developed BP and FP16 can maintain high-quality protein, and at the same time, reduce phosphate intake. It is advisable that the new BP and FP16 be taken together with the low-phosphorus milk we previously developed (low-phosphorus milk sold under the name L.P.K.).
Based on a questionnaire we concluded that BP and FP16 can be used effectively on a daily busis. The new foods to be eaten with them have also shown good results with patients.

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We have already reported that synthesis of guanidinoacetic acid (GAA) and creatine (CR) decreases in the course of renal damage; however, the serum CR level increases exponentially as serum GAA recovers to the normal level in patients on maintenance hemodialysis. From this point of view, we attempted to investigate the CR metabolism of skeletal muscle in uremia.
We measured the serum concentrations of urea nitrogen, creatinine, GAA, and CR in the femoral vein and artery of patients with chronic renal failure (CRF) on conservative therapy or maintenance hemadialysis, and patients with acute renal failure (ARF), in comparison with normal controls.
The patients with CRF on conservative therapy tended to have lower venous GAA and CR concentrations than normal controls, but the ratio of CR uptake in skeletal muscle was similar between the two groups. Patients with CRF on maintenance hemodialysis showed a similar level of venous GAA concentration to normal controls, but venous CR concentration in the former was significantly higher than that in the latter. The CR uptake ratio of skeletal muscle was lower than that with normal controls. Patients with ARF showed a significantly lower level of venous GAA concentration and CR uptake, but a higher level of venous CR concentration, than normal controls.
These results indicate that CR might be released from the skeletal muscle, resulting in a higher concentration of serum CR in the uremic stage. The release of CR can be induced by altered permeability of skeletal muscle affected by deranged protein metabolism and the retention of uremic toxins in certain uremic patients. However, certain substances might inhibit CR uptake into the skeletal muscle cell in uremia.

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We examined the relationship between spleen size and various parameters, such as age, hemodialysis period, etiology, hemoglobin concentration, leukocyte count andt platelet count, in 137 hemodialysis patients, 83 men and 54 women. None of the patients had a history of chronic infectious disease or liver dysfunction. We measured spleen size by ultrasonography and used this measurement as the spleen index. Our patients' mean age was 48.9±11.0 (SD) years and duration of hemodialysis was 57.9±41.6 months. The underlying renal diseases were chronic glomerulonephritis in 98 patients, diabetic nephropathy in 21, polycystic kidney disease in 10, and other renal diseases in 8.
The spleen index was 1536±736 (SD), hemoglobin concentration 7.9±1.9g/dl, leukocyte count 5620±1666/mm³, and platelet count 17.4±5.6×10⁴/mm³. Splenomegaly was detected in 37 of 137 hemodialysis patients. The period of hemodialysis correlated positively with the spleen index (r=0.212; p<0.01) age, leukocyte count, and platelet count correlated negatively with the spleen index (r=-0.322; r=-0.269; and r=-0.391, respectively; p<0.01 in each instance). There was no significant correlation between the hemoglobin concentration and the spleen index. Among the three underlying renal disease groups, the mean spleen index was not significantly different when age and period of hemodialysis were matched.
These data suggest that splenic enlargement may be attributed to the process of hemodialysis itself and that splenic hypersequestration of damaged erythrocytes may develop and leukocytopenia and thrombocytopenia may progress by hypersplenism.

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There has been a continuous increase in diabetics among new dialysis patients. Although the survival of diabetics undergoing dialysis has been improving because of continued progress in dialysis technology and CAPD, there are still many unsolved problems concerning complications such as cardiovascular disturbances, retinopathy and neuropathy. We previously reported the clinical features, complications and couse of death among diabetics with dialysis in Hyogo Prefecture.
This time, we performed a clinical survey on 18 diabetic patients: 10 men and 8 women, average age 59.2 years, 6 patients with IDDM and 12 with NIDDM. The interdialytic weight increase was less than 3kg, CTR was 53%, and blood pressure was 150/71mmHg. These were maintained under reasonable control. FBS (148.3mg/dl), HBA_1c (7.2%), serum cholesterol (168.6mg/dl) and triglyceride (152.9mg/dl) were somewhat higher than normal, whereas HDL (33.5mg/dl) was slightly low. Ten of the 18 patients retained their eyesight. C-PTH was 4.4ng/ml, not especially high, but 9 of the 18 patients demonstrated renal osteodystrophy.

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Five of 24 patients (20%) who had been undergoing CAPD for more than three years between 1980 and 1988 in the Kidney Center of Tokyo Women's Medical College showed markedly decreased peritoneal ultra filtration (UF).
From the point of view of clinical findings, three of them (60%) had a history of more than two episodes of peritonitis, and three of them (60%) had frequently used hyperosmotic dialysate for two years during the initial phase. All patients with markedly decreased UF were associated with accerelated dextrose reabsorption on the peritoneal equilibrium test. As pathological findings, diffuse disappearance of mesothelium and microvilli, and géneralized thickness of the submesothelium tissue and fibrous layer were recognized in patients with decreased UF.
These results suggest that decreased UF is related to the frequency of peritonitis and the use of hyperosmotic dialysate. Changes in the mesothelium may accelerate dextrose reabsorption.

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Questionnaires were sent to 1, 808 dialysis units, urological departments and transplant centers in Japan in February, 1988, to determine the present status of renal cell carcinoma in chronic hemodialysis patients. The response rate of 70% covered about 70% of the 80, 553 dialysis patients in Japan. Renal cell carcinomas were found in 115 dialysis patients between March 1986 and February 1988. The mean age of the 115 patients (91 males and 24 females) was 51.4±11.5 (mean±S. D.) years. The mean duration of dialysis was 94.6±54.5 months. The initial clinical diagnosis of renal cell carcinoma was based on sonographic examination (47 cases) and computed tomography (38 cases). The original kidney disease was chronic glomerulonephritis in 89 cases, diabetic nephropathy in 10 and polycystic kidney disease in 4. Acquired renal cystic disease was found in 92 of 115 renal cell carcinomas. Curative nephrectomy was performed in 77 patients. The mean diameter of the renal cell carcinoma was 4.6±3.4cm. However, 17 of 106 patients had metastasis. Thirteen of 17 patients were males; their mean age was 57.8±12.0 years, mean duration of dialysis 83.2±44.4 months and tumor size 8.8±5.4cm in diameter. Acquired renal cystic disease was found in 10 of 17 metastatic renal cell carcinomas.
In conclusion, as of February 1988, 234 renal cell carcinomas have been reported in patients undergoing hemodialysis.

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We report an autopsy case of a systemic amyloidosis patient who was treated with hemodialysis due to chronic renal failure for 8 years and 7 months. The woman received the first hemodialysis treatment when she was 60 years old. After 6 months, she required implantation of a permanent pacemaker for the treatment of sick sinus syndrome, but pacing failure often occurred. Five months later, she underwent cholecystectomy with liver biopsy, which demonstrated the deposition of amyloid (AA) in the liver tissue. The diagnosis of secondary amyloidosis associated with chronic cholecystitis was thus made. She was hospitalized 12 times because of complications such as pacing failure, congestive heart failure and shunt occlusion. Hypotension was sometimes too serious for hemodialysis to be continued. It was suggested that the hypotension was due to the decrease in cardiac output and peripheral vascular resistance. Itching persisted in spite of treatment, and the deposition of amyloid was demonstrated in one of three skin biopsies.
The patient died when she was 69 years old, and it was found by autopsy that the pacemaker had perforated through the right ventricular wall.

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