We analyzed changes in serum and urinary β₂-microglobulin (β₂-MG) in 457 hemodialysis patients (HD-Pt), 19 renal transplant patients (Tx-Pt) and 16 esophageal cancer patients (EC-Pt) with surgery. This study was undertaken to investigate estimated β₂-MG filtration per glomerulus per day, and to examine the possibility of eliminating β₂-MG using hemopurification and treating dialysis-related amyloidosis after renal transplantation.
Serum β₂-MG values of HD-Pt were higher in younger patients, women, and patients who had undergone HD for ten years and whose urine volume was less than 100ml a day.
Estimated amounts of β₂-MG that filtered through the renal glomeruli in one day were 162mg in Tx-Pt, 178mg in EC-Pt before surgery and 119 to 241mg in EC-Pt after surgery. If daily β₂-MG production were 180mg, the amount of β₂-MG eliminated by the end of hemopurification should be at least 500mg. However, this target will not be achieved in the near future.
As the β₂-MG level of HD-Pt was ten times that of Tx-Pt, urinary excretion of β₂-MG is sufficient in Tx-Pt. However, from our result and other reports, renal transplantation did not improve cystic radiolucency of the wrist joints in Tx-Pt.

View full abstract

The production of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced by lipopolisaccharide (LPS) and 4β-phorbol 12β-myristate 13α-acetate (PMA) were examined to evaluate the influence of uremia and hemodialysis on the capacity of peripheral blood monocytes in patients with chronic renal failure (CRF). Peripheral blood monocytes were prepared from 5 patients with stable end-stage renal disease (ESRD), 6 patients undergoing intermittent hemodialysis (HD) and 3 healthy controls, by Ficoll-Conray gradient centrifugation. Monocytes were incubated with LPS 20μg/ml for IL-1β and LPS 20μg/ml;+PMA 10μg/ml for TNF-α for 16 hours. Enzyme-linked immunosorbent assay was used to measure IL-1β and radioimmunoassay to measure TNF-α. The production of IL-1β and TNF-α from the peripheral blood monocytes was significantly less in ESRD patients than in healthy controls. The production of IL-1β and TNF-α in HD patients was higher than in ESRD patients. From these results we concluded that the capacity of peripheral blood monocytes was recovered with the initiation of HD in ESRD patients.

View full abstract

In order to evaluate arrhythmias associated with hemodialysis (HD), 117 patients on maintenance hemodialysis were studied on the basis of 24-hour ambulatory electrocardiographic recordings. In this study, 30% of the HD-patients exhibited the “hemodialysis-induced arrhythmias” (HDA), i.e., their arrhythmias were aggravated during or within 4 hours after HD. Ventricular premature contractions (VPCs) accounted for 80% of the aggravated arrhythmias in the HDA patients, and 57.1% of them consisted of supraventricular premature contractions (SVPCs). With regard to the VPCs, 48.6% of the HDA patients belonged to higher risk Lown classes (≥3). Serum calcium concentrations were significantly lower before HD in the HDA group than in the group with “non hemodialysis-induced arrhythmias” (NHDA) (p<0.01). Thus, the increase in extracellular calcium concentration must have been higher in the HDA-group during HD than in the NHDA-group. Consequently, the premature contractions in the HDA patients may have been induced by “triggered activity” which occurred when extracellular calcium concentrations reached high levels. The HDA patients were also older and had a higher incidence of complication by cardiovascular disease and diabetes mellitus (p<0.05), so myocardial damage may be associated with HDA. On the basis of analysis using a multiple logistic model, age (p=0.023) and pre-HD hypocalcemia (p=0.034) were identified as significant factors associated with HDA. While no aggravation of arrhythmias was detected in patients on HD using low calcium and low potassium dialysate, attention to calcium and potassium concentration in the dialysate is necessary in patients with poor cardiac function.

View full abstract

Hemodialysis (HD)-induced hypotension (HIH) is a serious complication in patients with maintenance HD therapy. Droxidopa (DOPS), a synthetic precursor amino acid of norepinephrine (NE), had already been found to be effective for hypotensive episodes of amyloidosis or Shy-Drager syndrome. We have reported its efficacy for HIH in some patients in our center. In this study, we evaluate the clinical effect in a multicenter trial.
The subjects were 34 cases (male 14, diabetic renal failure 12) with HIH in 5 HD centers. DOPS (200-400mg) was administered orally 1 hr before the initiation of HD. The clinical effect of DOPS was evaluated on the basis of its prevention of HIH, the volume of saline or 10% NaCl and other treatments for HIH, and the improvement of subjective or objective symptoms.
With DOPS administration, HIH improved in 23 cases (67.6%). The symptoms due to HIH improved in 25 cases (73.5%). The volume of administered saline or 10% NaCI for HIH decreased significantly. Furthermore, subjective improvement continued even after the HD session was completed in 22 cases (64.7%). Although mild side effects occurred in 3 cases, these disappeared after the dosage was decreased. There was no definite difference in the efficacy of DOPS related to the patients' age, sex, length of HD, the level of NE before the initiation of HD, though DOPS was less effective for diabetic or severe HIH patients.
In conclusion, oral DOPS therapy was very effective for HIH, especially in non-diabetic patients.

View full abstract

The effects of exercise training on exercise capacity were evaluated in 8 regular hemodialysis patients whose anemia was partially improved by treatment with recombinant human erythropoietin (rEPO). A 12-week exercise training program was started using a bicycle ergometer. A symptom-limited exercise tolerance test was performed before and after the program. Serial measurements of blood gases, arterial lactate values and expiratory gas were made during the test. Hemoglobin values were maintained constant. PaO₂ and PaCO₂ did not change significantly during the test. Exercise time was lengthened from 13.2±1.8 to 15.8±1.2 min (p<0.01), but maximum O₂ uptake did not increase significantly. Maximum arterial lactate values rose significantly from 3.6±2.0 to 4.4±1.4mM (p<0.05). Although the exercise capacity of regular hemodialysis patients treated with rEPO improved, their aerobic exercise capacity did not improve significantly. Maximum arterial lactate values, on the other hand, did increase. These results indicate that improved exercise capacity was not the result of an improvement in aerobic energy production but in anaerobic energy production. A surprisingly low O₂ uptake in terms of a markedly increased O₂ supply indicates that hemodialysis patients have (a) defect (s) in the aerobic energy production system of their skeletal muscle.

View full abstract

Although the development of hemodialysis has allowed patients with end-stage renal diseases to survive for a long time, ischemic heart disease has become an important factor in their mortality. Coronary artery bypass surgery, however, is still considered a highly risky procedure in these patients. We examined the results of percutaneous transluminal angioplasty (PTCA) performed between 1987 and 1989 in 7 consecutive patients with angina pectoris and chronic renal failure requiring hemodialysis. They consisted of five men and two women with a mean age of 56.8 years, and included three patients with diabetic nephropathy, two with chronic glomerular nephritis, one with polycystic kidney and one with nephrosclerosis. Three patients had previous myocardial infarctions. Angiographic success was achieved in 16 of 18 (89%) stenotic sites attempted. There were no inhospital deaths or acute myocardial infarctions, although one patient died of congestive heart failure one week after discharge in spite of successful PTCA. Recurrent angina developed in 3 patients within 7 months after successful PTCA. Re-angiography in these 3 patients demonstrated restenosis at 2 of 7 (29%) dilated sites. We successfully performed repeat PTCA of all restenotic lesions.
Our findings show that PTCA in chronic hemodialysis patients is effective and as low-risk as in non-dialysis patients.

View full abstract

A test kit for detecting leukocyturia, Leukostix^®, has been used for all patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in our hospital to make the diagnosis of CAPD peritonitis.
These CAPD patients used Leukostix^® every morning at home. Sixteen CAPD patients with suspected CAPD peritonitis were analyzed.
We evaluated the relationships between the results of Leukostix^® and clinical symptoms, cloudy effluent, leukocyte counts in the effluent and peripheral blood, and estimated the usefulness of Leukostix^® for early diagnosis of CAPD peritonitis.
Leukostix^® was positive in 14 of 16 patients who were diagnosed as having CAPD peritonitis (92%). A positive correlation was observed between the grade of Leukostix^® and the leukocyte count in effluent.
Nine patients with CAPD peritonitis were positive on the Leukostix^® test, with symptoms of peritonitis and cloudy effluent.
One patient who showed a positive Leukostix^® result without symptoms of peritonitis or cloudy effluent was diagnosed as having CAPD peritonitis by other examinations. The sensitivity and accuracy of Leukostix^® were better than those of other parameters.
These results suggest that Leukostix^® is a simple and useful method for the early diagnosis of CAPD peritonitis.

View full abstract

The clinical effects of short time biofiltration (BF) with a high-performance membrane dialyzer (HPM) were compared with those of conventional hemodialysis with an ordinary membrane dialyzer (OD) and bicarbonate dialysate (BCHD) in 5 regular hemodialysis patients for 6 months. The treatment time of BF was determined by the urea index (UI), which was kept similar to that of BCHD. The treatment times were 3.4±0.25 hr with 235.0±17.3ml/min of blood flow in BF, and 4.8±0.25 hr with167.5±9.6ml/min in BCHD (p<0.05). During the 6 months of BF, the pre-BF concentrations of HCO₃ and β₂-microgloblin (β₂-MG) were significantly increased and decreased, respectively, compared to pre-BCHD levels. No significant difference was observed in pre-treatment levels of urea nitrogen (UN), creatinine (Cr), uric acid (UA) and electrolytes between the periods of BCHD and BF. The incidence and severity of dialysis disequlibrium symptoms (DDS), and the infusion volume and frequency required to treat DDS were comparable between the 2 periods. Although, no significant differences were noted in the eliminated amounts of UN, Cr, UA, β₂-MG, and electrolytes in the dialysates from short time BF and BCHD with a HPM, the reduction rates of β₂-MG and phosphate (P) showed higher values in the former than in the latter. These results indicate that short-time BF with a HPM can provide more beneficial effects than BCHD with an OD at least during 6 months of observation, and that the UI can be used to determine the treatment time of BF.

View full abstract

We experienced 3 cases of Guillain-Barré syndrome (GBS) with the grades higher than 4 in whom no effect was observed even with a conservative treatment. Paralysis of the respiratory muscles was observed in all 3 cases. As a result of performing double filtration plasmapheresis (DFPP) at an acute phase, remarkable improvement was seen, and we have, therefore, made an assessment regarding the effectiveness of DFPP to be performed at an acute phase of GBS which is an autoimmune disease.
Case 1 was a male aged 18 in whom weakness of the limbs and paralysis of the respiratory muscles were observed being in progress. No improvement was observed by a steroid pulse therapy, and a respirator was attached to each patient. By performing DFPP, spontaneous respiration was observed to occur during the treatment, and subsequently ambulation became possible. Case 2 was a female aged 22. A steroid pulse therapy was made due to ambulation having been not possible and exacerbated respiratory condition, but no effect was observed. After performing DFPP, the respiratory function improved, and the muscular strength was also gradually improved, having made ambulation possible. Case 3 was a male aged 26. A steroid pulse therapy was made for flaccid paralysis of the limbs and facial palsy in progress, but no effect was observed Restoration of the muscular strength was observed to occur during the treatment, and subsequently ambulation became possible. DFPP was performed continuously for 3 days, and 3l was treated pere.
All the 3 patients were severe cases in whom paralysis of the respiratory muscles was observed to develop comparatively rapidly after the onset and no effect was observed by the pulse therapy. However, it was considered that performance of DFPP at an early stage was effective also from the aspects of removing the causal substances and minimizing nerve demyelination and degeneration of the axial beam.

View full abstract

Factors affecting left ventricular hypertrophy were analyzed in 16 diabetic (DM) and 52 non-DM chronic hemodialysis patients. The DM patients showed significantly greater left ventricular mass index (LVMI), which was examined by M-mode echocardiography, in association with significantly higher systolic and mean blood pressure compaired with non-DM patients. Between the groups where mean blood pressure and duration of hemodialysis were matched, the LVMI was significantly greater in DM than non-DM patients. When the DM patients were divided into 2 groups according to the level of LVMI, the group having a larger LVMI, being 175g/m² or more, revealed a significantly higher hemoglobin A_1c than the group having less LVMI. These results suggest that the disorder of glucose metabolism may play an important role in the genesis of left ventricular hypertrophy in DM hemodialysis patients.

View full abstract

The potassium content in Tsumura Kampo Medicine preparations (Extract Granules for Ethical Use) was studied. Potassium was determined by flame spectrophotometry. Coefficients of variation for several lots of “Tsumura Kampo Medicine Sho-siako-to Extract Granules for Ethical Use” and “Tsumura Kampo Medicine Saireito Extract Granules for Ethical Use” were approximately 3% to 6%.
Eleven of 14 Kampo Medicine preparations were found to contain 15mg to 25mg of potassium per pouch containing 2.5g of the preparation, but “Tsumura Kampo Medicine Toki-inshi, ” “Tsumura Kampo Medicine Bofutsusho-san” and “Tsumura Kampo Medicine Hochu-ekki-to” (Extract Granules for Ethical Use) contained higher amounts of patassium: 40mg, 33mg, and 34mg per pouch, respectively.
The preparations “Tsumura Kampo Medicine Sairei-to” and “Tsumura Kampo Medicine Sho-seiryu-to” (Extract Granules for Ethical Use) were found to contain 29mg to 34mg of potassium per pouch containing 3.0g of the preparation.
When Kampo Medicine preparations are given to patients three times a day, total potassium intake is from 60mg to 100mg in most cases. On the other hand, about 1, 000mg of potassium is normally brought into the body each day through the intake of foods and beverages.
The amount of potassium from Kampo Medicine preparations is relatively small (less than 10%) compared with that from foods and beverages. Nevertheless, for the hemodialysis patient, who generally has an increasing blood potassium concentration, it is recommended that Kampo Medicine preparations be given carefully and that the dose of potassium be considered.

View full abstract

Hearing and vestibular complications are common in hemodialysis patients, but in this paper we present a rare case of sudden deafness.
A 55-year-old man with diabetic renal failure developed sudden right hearing loss and tinnitus after being on hemodialysis for 2 months. Otological examination revealed severe sensorineural hearing loss of 93.8dB. Treatment failed to improve either the patient's hearing loss or tinnitus. A circulatory disorder of the inner ear is speculated to have been the etiology in this case, since there was no evidence of viral infection.
Twenty cases of sudden deafness in hemodialysis patients, including our own case, were collected from Japanese publications and reviewed.

View full abstract

The case of a 63-year-old Japanese man with acute renal failure, in whom maintenance hemodialysis was successfully withdrawn two years later, is reported. Renal biopsy revealed severe lymphocytic infiltration in the interstitium with almost normal glomeruli. His acute interstitial nephritis was possibly caused by either antibiotics or non-steroidal anti-inflammatory drugs, with which he had been treated for a high fever of unknown etiology.

View full abstract

A case is reported of diabetic nephropathy under-going 3-hour dialysis twice per week (6 hours/week) for a long time. Methods of short dialysis: Dialyzer F80 (Polysulfone, 1.9m², Fresenius) Blood flow 300ml/min (Internal A-V fistura). Dialysate flow 750ml/min (Kindaly AF). The sodium concentration of dialysate was 155mEq/l at the start of dialysis and was graduately reduced to 140 mEq/l at the end of each dialysis.
Residual renal function was checked by interdialysis (67 hours) urine collection and urea space was calculated by hemofiltration.
Results: There was almost no residual renal function (urine volume 300ml/67 hours). The urea space was 55% of the body weight. The urea index was calculated to be 1.52. That indicates adequate dialysis.
Observation of long term (more than one year) showed no remarkable changes in the pre dialysis BUN, Pi. The correction of electrolytes and the acid-base balance were sufficient. There were no problems in the control of BP, CTR and stopping the weight gain. The Ht and C-PTH remained unchanged. Our case suggests that some cases of diabetic nephropathy could be maintained under short-time dialysis.

View full abstract

Hypoglycemic attacks were observed in three patients with non-diabetic chronic renal failure on hemodialysis (HD). The third case is thought to be the first reported case of enoxacin-induced hypoglycemia.
Case 1. A 58-year-old man complained of sweating and fatigue two hours after the beginning of HD using a glucose-free bicarbonate dialysate. The patient had not eaten breakfast. He became unconscious and his blood glucose level was 65mg/dl His symptoms disappeared after an intravenous injection of glucose. Case 2. A 69-year-old woman was found comatose in the morning. Her blood glucose level was 40mg/dl and she needed frequent supplies of glucose for 24 hours because of prolongation of the hypoglycemic state. She had mistakenly taken an oral hypoglycemic drug as an antihypertensive agent. Case 3. A 78-year-old woman received 600mg of enoxacin under the diagnosis of urinary tract infection. Three days later she complained of sweating and palpitation, which disappeared only after meals. She became unconscious on the night of the fourth day and her blood glucose level was 20mg/dl Although transient recovery of hypoglycemia was observed after a bolus injection of glucose, the hypoglycemic state was prolonged until 13:00 the next day. Recurrence of hypoglycemic attack was not observed after the discontinuation of enoxacin, although she continued her other drugs. No organic disease was found to have induced the hypoglycemic attack in these three patients.
In three non-diabetic dialysis patients, hypoglycemic attacks were considered to be caused by a glucose-free diaiysate in case 1, misuse of an oral hypogycemic drug in case 2 and enoxacin in case 3.

View full abstract