Out of 480 uremic patients treated in our institute for the past 10 years, 24 patients developed malignant diseases, an incidence of 5.0%. The most frequently detected malignant tumor was liver cancer, accounting for 9 cases (8 males, 1 female). Seven cases had diabetes mellitus (DM) out of these 9 hepatic tumor cases. The liver cancer was detected at the initiation of hemodialysis or within one year after the initiation of hemodialysis in 6 of the 9. Surgical hepatectomy, transcatheter arterial embolization with intra-arterial infusion of anticancer agents, and percutaneous ethanol injection therapy were performed successfully in 7 cases. No significant complications of these treatments were noted except for hyperkalemia. Measurement of the serum α-fetoprotein (αFP) concentration, specifically, would be useful for diagnosing liver cancer and evaluation the clinical course of tumor development. Annual screening for liver cancer using ultrasonography and serum αFP measurement should be performed in uremic patients before the initiation of dialysis.

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To evaluate the merits of introducing plasma exchange for the treatment of collagen diseases and to assess the usefulness of this therapy, a retrospective study of 19 patients with collagen disease, consisting of eight rheumatoid arthritis (RA), three malignant rheumatoid arthritis (MRA), and eight systemic lupus erythematosus (SLE) patients, was undertaken to determine serological changes after this therapy and correlate the level of improvement in their clinical symptoms.
All eight RA patients underwent double filtration plasmapheresis (DFPP) therapy and four of these patients concomitantly received immunoadsorption (IA) therapy. All three MRA patients also received DFPP therapy, and two received IA therapy in parallel. The eight SLE patients included one who was receiving total plasma exchange (T. PE) therapy, whereas the remaining seven were given DFPP treatment, with three of this number simultaneously received IA therapy.
The reason for introducing plasma exchange therapy for the RA and MRA patients was that they had developed polyarthritic pains and manifested progressive renal disorders that were becoming increasingly resistant to palliative, preservative therapy; in the case of the SLE patients, this therapy was introduced because they too were manifesting progressive renal disorders that were becoming increasingly resistant to palliative, preservative therapy and one of them was presenting with complications of the nervous system. Thus, this therapy had been administered in the hope of achieving some improvement in these patients.
All of the RA and MRA patients, 11 in total, responded well to plasma exchange therapy, which resulted in either the alleviation or disappearance of their arthritic pains. However, in only five (45.6%) of these 11 patients was it possible to correlate the improvement in their arthritic symptoms with a post-therapeutic reduction in their blood RAHA level. As for the three MRA patients, one showed an improvement in renal function. With regard to the six SLE patients, five showed an improvement in renal function. Also, in six (75.0%) of these eight SLE patients, it was possible to correlate the extent of improvement in their clinical symptoms with a reduction in the anti-nuclear antibody and the anti-DNA antibody levels in their blood.
Based on these findings, the long-term prognosis of RA and MRA patients given this plasma exchange therapy appears encouraging, but regular maintenance therapy is required. For SLE patients, the long-term prognosis is even more favorable, with possible recovery after short-term treatment. Thus, these findings reflect the effectiveness of plasma exchange therapy.
It thus appears that for collagen disease cases that become resistant to palliative, preservative therapy, radical treatment in the form of plasma exchange therapy is definitely effective.

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We examined the efficiency and the mechanism of elimination of ioxaglate, a low-osmolality radiocontrast agent, by hemodialysis. Ioxaglate (20ml of hexabrix^® 320) was administered intravenously to 4 patients undergoing maintenance hemodialysis. Hemodialysis was performed for 4h (Q_B=200ml/min and Q_D=500ml/min) with regenerated cellulose-membrane dialyzers (AM-SD-15H or its high-flux type, AM-Neo-2001UP; each surface area, 1.5m²). Blood was sampled from both the inlet and the outlet of the dialyzer during hemodialysis. Dialysate passing through the dialyzer was also collected. Clearances (CL [ml/min]) of urea nitrogen (UN), creatinine (Cr), and ioxaglate were calculated from the differences of each plasma solute content between the inlet and the outlet of the dialyzer (CL_B) and also from the solute content of the dialysate (CL_D). The reduction rate (RR[%]) of ioxaglate during hemodialysis with AM-SD-15H was 78±5% (mean±SD) and was significantly higher than both RR_UN (65±4%) and RR_Cr (61±4%). With AM-Neo-2001UP, RR_ioxaglate (81±3%) was also significantly higher than both RR_UN (68±5%) and RR_Cr (62±4%).
With AM-SD-15H, CL_B of ioxaglate, UN, and Cr were 103±11, 174±5, and 143±9ml/min, respectively. CL_B of these solutes with AM-Neo-2001UP were 127±4, 188±2, and 146±6ml/min, respectively, and significantly larger than those with AM-SD-15H, except for Cr.
The CL_D of ioxaglate was 61±14ml/min with AM-SD-15H and 85±18ml/min with AM-Neo-2001UP, significantly smaller than each CL_B, indicating that 40% and 33% of the ioxaglate CL_B corresponded to adsorption to the membrane of each dialyzer.
With either AM-SD-15H or AM-Neo-2001UP, the CL_B of ioxaglate did not change significantly with different ultrafiltration rates.
It is concluded that ioxaglate can be efficiently eliminated by hemodialysis, the efficiency of which is slightly better with a high-flux type dialyzer than with a conventional, regenerated cellulose-membrane dialyzer. It is suggested that not only diffusion but also adsorption plays an important role in the elimination of ioxaglate by hemodialysis.

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Marked improvements in anemic patients who are on hemodialysis have been produced by erythropoietin (EPO) therapy. There are, however, patients who complain of hypertension and headache after receiving EPO therapy, and some patients for whom EPO therapy is not effective. Thus, instead of increasing the EPO dosage, another therapy for improvement of anemia is required. Attacks of reactive oxygen species (ROS) produce membrane injury, which results in a shortened erythrocyte life span, which in turn is a cause of anemia in patients on maintenance dialysis. Therefore, α-tocopherol (TOC), an anti-oxidant drug, was given to patients and laboratory studies were done. As a result, values of a thiobarbituric acid (TBA) reactive substance in plasma and erythrocytes decreased, and the glutathione peroxidase activity of erythrocytes increased. In addition, tendencies for improved erythrocyte counts, hemoglobin levels, and hematocrit were evident. These results suggest that Toc therapy reduces peroxidation of cell membrane lipids which protects erythrocyte membranes from the attacks of ROS; this will lead to improvement of anemia and inhibit arteriosclerosis which is frequently seen in patients with maintenance hemodialysis.

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In order to eliminate the need for hospitalization in the treatment of CAPD peritonitis, we have designed outpatient protocols I and II.
A total of 72 consecutive episodes of CAPD peritonitis treated in our hopital during the period from April 1988 to March 1993 were treated in accordance with these protocols.
Protocol I was started just after the onset of peritonitis before the results of bacteriologic examinations had been obtained. On the first day the patients were given intraperitoneal doses of vancomycin (VCM: 30mg/kg body weght) mixed into 2l of PD fluid, intramuscular doses of aminoglycosides and daily oral doses of neuquinolones. The patients were subsequently sent home with instructions to drain the peritoneal fluid after 6 hours and to resume their previous CAPD schedule. The clinical course was checked by telephone every morning. The patients returned to our hospital on the 8th day and given second intraperitoneal doses of VCM and intramuscular doses of aminoglycosides in the same manner as on the first day. In the cases of either gram negative bacilli being cultured or no improvement of cloudy drainage fluid within a week, we changed the protocol from I to II, which consisted of administration of ceftazidime and aminoglycosides on daily hospital visit.
Of the 72 episodes, 64 (88.8%) were successfully treated on this protocol and did not require hospitalization. Eight patients, however, did not respond to this protocol and were admitted in order to remove the catheter. In 59 patients (81.9%) who were treated successfully on protocol I, the cloudy drainage fluid disappeared within 2.8±1.3 days and they required only 2 hospital visits.
In conclusion our protocol has proven effective, simple and easy to perform on an outpatient basis and is valuable in the treatment of CAPD peritonitis.

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The present study was conducted to elucidate the mechanism of the effects of fat emulsion on pruritus cutanea in chronic hemodialysis (HD) patients.
Fasting fatty acid fractions of serum total lipids in 3 end stage renal disease (ESRD) patients and 8 HD patients were measured. All fatty acid components were normal in ESRD patients, but low in HD patients. This tendency was remarkable for linoleic acid: the referential normal range was 4.53-8.20μmol/l, while ESRD patients registered 4.39±1.17μmol/l and HD patients showed 2.76±0.30μmol/l. When HD patients were divided into two groups based on those that experienced itching and those that did not, a comparison revealed no significant difference in fatty acid concentration between the two groups. Fat emulsion (Intralipos^®20% 200ml) was administered intravenously to all HD patients during hemodialysis twice a week for four weeks; a total of eight times, and the degree of itchiness and fasting fatty acid fractions of total lipids were evaluated prior to the first injection, at the end of injection, and at four weeks after the final injection. An alleviation of itching was observed in all patients, and this effect was sustained even four weeks after the final injection. No significant change, however, was observed in serum fatty acid fractions.
It is accordingly concluded that the low levels of serum fatty acid fractions do not play an important role in the development of pruritus cutanea, and that the fat emulsion induced alleviation of itching is not associated with alterations of serum fatty acid fractions in chronic hemodialysis patients.

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In order to determine the clinical significance of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients undergoing maintenance hemodialysis, we examined myeloperoxidase specific ANCA (MPO-ANCA) and proteinase 3 specific ANCA (PR3-ANCA) by enzyme immunosorbent assay in 183 patients undergoing maintenance hemodialysis for more than a year. Eleven patients had ANCA, 8 with MPO-ANCA and 4 with PR3-ANCA including one with both MPO-ANCA and PR3-ANCA. These ANCA positive patients were divided into two groups (3 patients in A group and 9 in B group) by the history of rapidly progressive glomerulonephritic syndrome (RPGN). All of A group with RPGN had vasculitic syndrome at the start of hemodialysis. One had a relapse of pulmonary hemorrhage with MPO-ANCA after 3 years of uneventful maintenance hemodialysis without MPO-ANCA. Although the remaining 2 patients had MPO-ANCA continuously, they had no remarkable vasculitic syndrome during maintenance hemodialysis. B group, without RPGN, had no history of vasculitic syndrome. The pathogenesis of ANCA production in B group might be related to immunological abnormalities associated with chronic renal failure or maintenance hemodialysis.
In ANCA positive patients undergoing maintenance hemodialysis with a history of RPGN, careful management to prevent the occurrence of vasculitic syndrome, especially pulmonary hemorrhage, is needed.

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With the increase in the number of long-term hemodialysis patients, dialysis amyloid osteoarthropathy has attracted attention as a serious complication. We evaluated the presence of amyloid in the synovial fluid of 8 patients on maintenance hemodialysis showing retention of synovial fluid due to gonarthritis (2 males and 6 females; mean age, 65.9 years; mean duration of hemodialysis, 106 months). In addition, the β₂-microglobulin concentrations in the synovial fluid and serum were measured. Similar examinations were performed on the synovial fluid in controls with normal renal function. Staining for amyloid showed the absence of amyloid in the control group while it was present in 6 of the 8 patients on maintenance hemodialysis. The mean duration of hemodialysis in the 6 patients was 132.0 months. Carpal tunnel syndrome as a complication was observed in 4 of the 6 patients, suggesting typical synovial amyloidosis. However, amyloid was also detected in a patient with a short duration of dialysis (61 months). This finding suggests that amyloid deposition in the articular synovium occurs in a relatively early stage after introduction of hemodialysis. In this patient, no clinical symptoms except gonarthritis are observable at present, but other symptoms are expected to develop with prolongation of the duration of hemodialysis. In the maintenance hemodialysis patients, the β₂-microglobulin concentration in the synovial fluid (18.3±4.9mg/l) was significantly lower than the serum β₂-microglobulin concentration (31.5±7.6mg/l). In the control group, no significant difference was observed between the synovial and serum concentrations. These findings suggest the presence of proteinase in the synovial fluid in maintenance hemodialysis patients showing arthritis. However, in patients showing deposition of a large amount of amyloid in the articular synovium, dilution due to impaired transfer by tissue fluid caused by circulation failure in the blood and lymphatic vessels is also possible. A significant positive correlation was observed between the serum and synovial β₂-microglobulin concentration in both control and dialysis patient groups.

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Thyroid function was investigated in 63 patients on chronic dialysis, consisting of 53 hemodialysis and 10 CAPD cases. Original causes of chronic renal failure were chronic glomerulonephritis (CGN) (n=35), diabetes mellitus (DM) (n=18) and others. All cases filled out questionnaire surveys on subjective symptoms and serum free triiodothyronine (F-T3), free thyroxine (F-T4), thyrotropin (TSH), thyroglobulin antibody and microsome antibody levels were determined. In addition, total triiodothyronine (T-T3), total thyroxine (T-T4) and thyroxine binding globulin (TBG) in serum were also measured in 35 patients younger than sixty-five years old. A given amount of thyroid hormone preparation was administered to the other patients to analyze the kinetics of thyroid hormone concentrations, and to investigate whether their clinical symptoms improved or not. Subjective symptoms of these patients were very similar to those of hypothyroidism. Antithyroid antibodies were negative except in two patients, indicating no complications of chronic thyroiditis. Serum F-T3 and F-T4 in all patients were 1.6±0.7pg/ml and 0.55±0.26ng/dl, respectively. These values were much lower than normal, indicating that these patients were in a hypothyroid state. On the other hand, serum TSH levels in all patients were higher than normal (10.81±33.2μU/ml), with large variations. To investigate this variation further, they were subdivided into two groups, those with normal TSH and those with high TSH. DM patients were mostly found (p<0.005) in the high TSH group, as compared to normal. Moreover, the serum TSH level was significantly higher in DM patients than in CGN patients (30.5±58.6 vs 3.1±2.3μU/ml, p<0.01). Serum F-T3 and F-T4 levels were significantly lower in DM patients than in CGN patients (1.2±0.7 vs 1.7±0.7pg/ml, p<0.05 and 0.4±0.2 vs 0.6±0.3ng/ml, p<0.005, respectively). These results suggested that the DM patients might be classified into a specific category with respect to hypothyroidism patients. Some of the other patients in the hypothyroid state on chronic dialysis were experimentally placed on dried thyroid powder or Thyradin S^®. The use of dried thyroid powder was considered to be preferrable and more effective than that of Thyradin S^®, because the latter did not cause an elevation in the F-T3 level.

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Intravenous reinjection of ascitic fluid after its filtration and concentration was performed to prevent pulmonary edema in patients with intractable ascites resistant to medical therapy. After reduction of the ascitic fluid volume, a peritoneo-caval shunt was created, using a LeVeen's pump, such that the ascitic volume could be semipermanently reduced.
Six patients including 4 males and 2 females, whose ages ranging from 42 to 65 years old (mean age: 55.3 years old), were evaluated with regard to the effects of this mode of combination therapy. Ascites resulted from chronic renal failure in 2 patients, from liver cirrhosis in 2, from gastric cancer in 1, and from uterine cancer in 1.
The ascites was treated by a Plascit-01 system (Asahi Medical Co.). Filtration was done using an AHF-MA filtration system and subsequent concentration was achieved with an AHF-UN concentration system. Two to 4 liters of the recovered ascites were filtered and concentrated to 100-200 mililiters, and intravenously reinjected into the patients in 4-7 divided doses (mean number of doses: 4.8). Subsequently, an ascites shunt was created between the peritoneal cavity and the superior vena cava.
Of the 6 patients evaluated, 5 died. Survival was prolonged from 1 to 3.5 years in our patients (mean duration of prolonged survival: 2.3 years) with the use of these combined methods. Symptoms were also ameliorated during the period of prolonged survival. The one remaining patient is presently on hemodialytic therapy and in stable clinical condition 4.2 years after undergoing combined treatment. No complications were noted in our patients while they were being treated with either the intravenous reinjection of ascitic fluid or the shunt creation procedure.
Our findings showed that the combination of intravenous reinjection after filtration and concentration of ascites and creation of a peritoneo-caval shunt is more effective and safer than either one of the 2 forms of treatment used alone for treatment of patients with intractable ascites.

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A 59-year-old woman had a 17.5-year history of dialysis and thrombocytopenia. She underwent total hip joint replacement due to left-side amyloid malumcoxae on July 8, 1992. After the operation, she developed a giant hematoma, drug-induced liver dysfunction, and disseminated intravascular coagulation (DIC). During the treatment of these complications, she had episodes of fever, jaundice, confusion, and anemia. In addition, her thrombocytopenia become worse. She was strongly suspected to have developed thrombotic thrombocytopenic purpura (TTP) and underwent plasmapheresis starting August 31, 1992. However, she died in September.
Bone marrow aspiration showed hypoplasia of megakaryocytes, erythroblasts, and leukocytes. There have been few reports of dialysis patients who developed TTP and bone marrow findings have not previously been documented. Our patient had idiopathic thrombocytopenic purpura preoperatively, and her TTP may be attributable to operative invasion, giant hematoma, DIC, or liver dysfunction.

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A 38-year-old female patient, who had been undergoing maintenance hemodialysis therapy since March 1987 because of chronic renal failure due to IgA nephropathy, is presented. She had gradually developed difficulty in walking since two years after starting hemodialysis therapy, and was diagnosed as having limb-girdle myodystrophy on examination.
Her course was complicated by myoglobulinemia because myoglobulin was produced in large quantities due to rhabdomyolysis associated with limb-girdle myodystrophy and urinary myoglobulin excretion was decreased due to chronic renal failure associated with IgA nephropathy.
After blood purification was changed from hemodialysis (HD) to hemodiafiltration (HDF) and membrane of dialysis was changed for improvement of myoglobulinemia, the concentrations of myoglobin in her blood and urine decreased, urine volume increased and uremia improved slightly. Then, the blood purification frequency was decreased from three times to twice a week. We speculate that urine volume increased because renal tubule damage by myoglobulinemia was reduced with the introduction of membrane and hemodiafiltration.

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A dialysis patient who showed gingival hyperplasia with calcium-antagonists, nifedipine (NFD) and manidipine (MND), is reported. A 64-year-old male who had received maintenance hemodialysis for 12 years was given antihypertensive therapy with NFD. Painless gingival hyperplasia developed one year later and NFD was discontinued after a further 7 months of administration. After MND was administered instead, gingival hyperplasia was alleviated transiently but was aggravated after 7 months of the MND therapy.
The prevalence of gingival hyperplasia induced by NFD has been reported to be 6.5-14.7%. Few cases of gingival hyperplasia caused by other calcium-antagonists (diltiazem, nicardipine, verapamil) have been reported and this is the first report of gingival hyperplasia induced by MND. The principal mechanism for gingival hyperplasia by calcium-antagonists has been suggested to be accumulation of extracellular matrix because calcium-antagonists decrease the breakdown of collagen due to the decreased influx of calcium ions into fibroblasts. Allergic reaction may be considered as another trigger for the occurrence of gingival hyperplasia.

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