Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD, as well as during the interdialytic period. L-threo-DOPS (L-DOPS), a synthetic precursor amino acid of noradrenaline, is converted into I-noradrenaline in the body after oral administration. We have reported high efficacy of L-DOPS on OH and OH-related subjective symptoms in the postdialysis period in HD patients. This study was conducted to confirm the efficacy of L-DOPS in a placebo (P)-controlled double-blind study. 400mg of L-DOPS or P was given to 107 HD patients with severe OH. The drug was administered orally 30minutes before the start of each HD period for 4 consecutive weeks. OH was significantly improved in the L-DOPS group, but not in the P group. Also L-DOPS significantly ameliorated subjective symptoms related to OH, including general fatigue and dizziness. This effect lasted throughout the interdialytic period. In contrast, no effect was observed in the P group. The global improvement rating was evaluated on the basis of changes in OH and OH-related symptoms. The percentages of patients with moderate or greater improvment were 53.3% in the L-DOPS group versus 14.6% in the P group. The incidence of untoward effects was comparable in the two groups and the side effects of L-DOPS were not serious. These results indicate that L-DOPS is highly effective for improving OH and OH-related interdialytic subjective symptoms in HD patients with severe OH.

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Bone-type alkaline phosphatase (bone ALP) measured by ELISA, ALP3 measured by electrophoresis on an cellulose-acetate membrane, and serum total alkaline phosphatase were evaluated in patients under renal replacement therapy.
Intact PTH, BGP, and intact BGP showed the highest correlations with bone ALP among the ALPs measured by the three different methods (ALP vs intact PTH: r=0.497; ALP3 vs intact PTH: r=0.427; bone ALP vs intact PTH: r=0.667; BGP vs ALP: r=0.548; BGP vs ALP3: r=0.505; BGP vs bone ALP: r=0.750) (intact BGP vs ALP: r=0.421; intact BGP vs ALP3: r=0.414; intact BGP vs bone ALP: r=0.680). In 32 hemodialysis patients with relative hypoparathyroidism (serum intact PTH concentrations below 200pg/ml), total ALP and ALP3 were not significantly correlatied with intact PTH, but bone ALP was (r=0.43, p<0.01).
These findings suggest that bone ALP measured by the ELISA method is a useful bone metabolic marker for assessment of bone turnover, particularly in patients with hypoparathyroidism.

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It has emerged that hyperhomocysteinemia is one of the risk factors for the development of atherosclerotic vascular disease. Hyperhomocysteinemia has also been observed in patients with end stake renal disease and on dialysis. We used the oral methionine loading test to determine the etiology of the complicating hyperhomocysteinemia in patients on dialysis. Sixteen CAPD patients, 14 HD patients and 15 healthy controls received 0.05g of methionine per kg of body weight after fasting for 12hours. The plasma levels of methionine, cystathionine and cystine were measured by the ninhydrin method, and plasma levels of total homocysteine were determined by the fluoro-HPLC method. CAPD patients exhibited significant increases in plasma total homocysteine, decreases in plasma methionine and increases in plasma cystine. HD patients showed a similar tendency. The methionine loading test revealed retention of plasma methionine, and consecutive increases in plasma homocysteine, cystathionine and cystine in both CAPD and HD patients. These observations suggest that patients on dialysis have specific impairment in the transsulfuration pathway. Considering the decrease in plasma methionine and increase in plasma cystine, patients on dialysis may have an impairment in remethylation from homocysteine to methionine which may play a role in the development of hyperhomocysteinemia.

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We measured trabecular and cortical bone mineral density (BMD) of lumbar vertebrae separately by quantitative computed tomography (QCT), including serum parameters of bone metabolism. The relationship between BMD of lumbar vertebrae and those parameters were investigated. The study was conducted on 74 male patients on chronic hemodialysis (HD) and 31 normal controls (N). We measured trabecular and cortical BMD of lumbar vertebrae L2-L4 separately by QCT, including serum parameters of bone metabolism, such as serum calcium (Ca), phosphate (Pi), intact parathyroid hormone (i-PTH), bone alkaline phosphatase (B-ALP), osteocalcin (BGP) and tartrate resistant acid phosphatase (TRACP). Trabecular BMD decreased with age in both groups. On the other hand, cortical BMD decreased with the duration of HD. A significant positive correlation was found between trabecular BMD and cortical BMD in the HD group, but not in the N group. Concentrations of serum Pi, i-PTH and BGP were higher in the HD group than those in the N group, but concentrations of serum Ca, B-ALP and TRACP did not differ between the two groups. Serum parameters of bone metabolism correlated significantly with each other. Cortical BMD was significantly correlaed with serum parameters, but trabecular BMD was not. There were some differences between trabecular BMD and cortical BMD of lumbar vertebrae, reflecting aging, duration of HD and serum i-PTH.

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Serum levels of three markers of representative constituents of the basement membrane, lamininP₁, type IV collagen-7S and procollagen-III-peptide, were measured in healthy controls and in diabetic patients without overt nephropathy, with conservatively treated diabetic nephropathy, and with diabetic renal failure on maintenance hemodialysis. All, three markers were elevated according to the development of diabetic nephropathy, in order of renal failure on hemodialysis>diabetic nephropathy>diabetic patients without nephropathy>control. There were statistically significant differences not only between hemodialytic patients and controls, but also between hemodialytic patients and those with diabetic nephropathy (p<0.001). Clinical significance of these markers that reflected the histological change in the basement membrane was discussed since measurement of serum levels might provide some information different from that from BUN and creatinine measurement to determine the severity of diabetic nephropathy.

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Minimum doses of heparin were compared among eight different dialyzers in 33 maintenance hemodialysis patients who were not administered any drugs possessing antithrombotic action. Intradialyzer clotting was classified into four grades by postdialysis gross appearance. Grade 1: none to a few fibers clotted; grade 2: one third of the fibers clotted; grade 3: one half of the fibers clotted and grade 4: total clotting. Minimum doses were determined by reducing the heparin dose from 1000U/hr at a rate of 100U/hr/HD until the grade of intradialyzer clotting was changed from 1 to 2. The dose was highest in PS (polysulfone membrane from Kawasumi Chemical Co. Ltd.), and decreased in order as follows: KF (ethylene vinylalcohol copolymer membrane from Kurare Co. Ltd.); PAN (polyacrylnitryl membrane from Asahi Medical Co. Ltd.); B2 (polymethylmetacrylate membrane from Toray Medical Co. Ltd.); TF (saponified cellulose membrane from Teijin Co. Ltd.); PC (polyethylene-grafted celluose membrane from Asahi Medical Co. Ltd.); SD (regenerated cellulose membrane from Asahi Medical Co. Ltd.); and FB (celluose triacetate membrane from Nipuro Co. Ltd.). After the blood port angle of the dialyzer housing was changed from 18 degrees to 7 degrees, thrombogenicity of KF and PS, formerly requiring the highest doses of heparin, were markedly improved. Pre-dialysis kaolin-activated whole blood clotting time (KCT) was significantly correlated negatively with the minimum doses of heparin. These data suggest that the minimum dose of heparin, in other words, dialyzer antithrombogenicity, is influenced not only by membrane antithrombogenicity but also by the housing design of the dialyzer, especially the blood port angle. Predialysis KCT is a good indicator of patients' blood coagulability.

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We report a maintenance HD patient with allergy to EtO-sterilized needles. A 61-year-old man with chronic glomerulonephritis started on maintenance HD in January 1989. He began to have itching and swelling of the puncture sites of the arterio-venous fistula with eosinophilia in 1990. We suspected that the symptoms might be caused by allergy to povidone iodine or chlorhexidine digluconate, which were used to sterilize the puncture sites. Although we changed the puncture site, the same symptoms appeared at the new puncture site. In addition to eosinophilia, the serum level of total IgE elevated, and the IgE was EtO specific. On the basis of these findings, it was suspected that the symptoms were due to allergy to EtO-sterilized needles. After the needles were changed to autoclaved ones, his symptoms and eosinophilia completely disappeared. Since currently dialysis equipment is almost always autoclaved or gamma-ray sterilized, HD patients with EtO allergy have decreased. However, we should be alert to allergy to EtO like this case, because needles and catheters are still mainly sterilized with EtO.

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A 43-year-old women was admitted to our hospital because of progressive consciousness disturbance. She had been on dialysis since 1983. She had had an abdominal operation for small-bowel obstruction due to adhesions. In January 1995, she became disoriented and somnolent. These neuropsychiatric symtoms became more severe and she sometimes lost consciousness. On admission, she was disoriented and her hands flapped severely. No hepatomegaly or splenomegaly was found in her abdominal cavity but an operative scar was noticed. Laboratory data revealed normal liver function but a highly elevated blood ammonia level of 424μg/dl was detected. There was no evidence of viral hepatitis. A liver biopsy showed normal histology. Percutanous celiac and mesentric arteriographies were performed and a large shunt between the superior mesenteric vein and the inferior vena cava through the right ovarian vein was observed on a venous phase. A T1-weighed brain MR image demonstrated symmetrical high-signal intensity in the basal ganglia. Embolization using 4 coils to the shunt was successfully done and her consciousness disturbance completely disappeared in association with normalization of the serum ammonia level after the procedure. The neurological impairment with hyperammonemia seen in this patient was diagnosed as being caused by the portal-systemic shunt.

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We report a 68-year-old male patient who had been undergoing hemodialysis for 2 years. He was diagnosed as having RPGN because of the rapid deterioration of renal function and crescent formation of most of the glomeruli detected by renal biopsy. P-ANCA was as high as 122U/ml. Maintenance hemodialysis was initiated because his renal function did not improve with the administration of glucocorticoid. He had been well until he was admitted to our hospital 2 years later with morning stiffness, pain/swelling of finger joints and fever above 38°C. Laboratory findings showed a C-reactive protein level of 11.7mg/dl, rheumatoid factor of 283U/ml, and P-ANCA of 1660U/ml. RA was diagnosed, and his symptoms and laboratory findings improved markedly with the administration of glucocorticoid. It is suggested that ANCA-related vasculitis was probably involved in the etiology of RPGN and RA in this case.

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Sclerosing encapsulating peritonitis (SEP) is one of the most serious complications of CAPD. In order to revise the definition, diagnosis and therapeutic strategy of sclerosing encapsulating peritonitis (SEP) in patients on CAPD proposed last year, a consensus meeting on SEP was held in Tokyo, on November 8 and 9, 1996. We made minor changes concerning the definition and treatment of SEP for this year. SEP was defined as a clinical entity which develops persistent, intermittent and/or recurrent clinical symptoms due to adhesive bowel obstruction in patients receiving peritoneal dialysis. Its clinical features are nausea, vomiting and abdominal pain in all patients. In addition, we see malnutrition, weight loss, diarrhea, constipation, slight fever, bloody dialysate, localized or diffuse ascites and decreased bowel movement in some patients with SEP. An abdominal mass consisting of adhesive small bowel is palpable in such patients. Histologically, we observe peritoneal thickening and/or sclerosing peritonitis in peritoneal tissue specimens from patients with SEP. Radiological and ultrasonic evaluations are very helpful for the diagnosis of SEP. The basic strategy for the treatment of SEP is to sustain the rest of the bowel. Long-term intravenous hyperalimentation (IVH) therapy is effective for the treatment of patients with SEP. It was reported that steroid pulse therapy seemed to be effective in five cases from four hospitals. This therapeutic intervention as well as an immunosuppression regimen should be evaluated in a large patient population.
We also proposed criteria for discontinuation of CAPD in order to prevent the development of SEP. However, SEP showed heterogeneity in each patient. Therefore, we proposed only a basic strategy for treatment of SEP in this revised version. Further study is needed in this area.

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