Precise evaluation of the vasculature condition is the first step in the management of arterio-venous (AV) shunt problem. Shuntgraphy or digital subtraction angiography (DSA) using iodine contrast medium has been widely used for the diagnosis of AV shunt problems. Recently, Doppler ultrasonography (DUS) has been widely used for diagnosis because of its low invasiveness. Furthermore magnetic resonance angiography (MRA) with or without contrast medium, Gd-DTPA, has also started to be employed for this purpose in several institutions.
In this study, we compared the findings of MRA to those of DUS and DSA in 12 patients (5 males and 7 females) with AV shunt problems such as stricture and venous hypertension. Most of these patients were treated by interventional radiology (IVR) such as percutaneous transluminal angioplasty (PTA), but some underwent surgery. The average period between AV shunting and problem onset was 8.3 years. Ten of 12 cases were native AV shunts and the remaining two were graft AV shunts. The diagnosis based on MRA findings was consistent with the diagnosis by DSA in 88.9% and with surgical findings in 100% of the cases. The overall conformity rate was 91.7%, but the conformity between MRA and DUS was only 58.3%. Although the issue of high cost remains and the method requires the use of a small amount of contrast medium (Gd-DPTA), MRA is minimally invasive without radiation exposure and is a useful tool providing accurate diagnoses in patients with AV shunt problem.

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Very little has been reported in Japan about research into bioethics with respect for the patient's self-determination in withdrawing from stable hemodialysis (HD) treatment during the terminal stage of illness. We, therefore, conducted a survey among nephrologists (n=552) regarding their decisions whether to stop or continue HD for patients in the terminal stage of malignancy. We also surveyed their opinions about advance directive (AD), death with dignity and life with dignity.
Overall, 434 nephrologists (78.6%) returned questionnaires, and effective responses were obtained from 427 (77.4%). Currently AD and death with dignity are not legally permissable in Japan. When the patient has an AD, the number of nephrologists who answered that they would stop HD significantly increased in cases of family request to stop HD (48.0% vs. 78.9%) or to continue HD (0.2% vs. 2.6%). When it was assumed that stopping life-sustaining treatment was not legally prohibited and the patient has an AD, the number of responses indicating to stop HD further increased in cases of family request to stop HD (90.9%) or to continue HD (11.9%). The number of nephrologists who answered that they need an AD totalled 74.0% and those who believed in death with dignity totalled 83.1%, while the number of nephrologists who desired legislation regarding AD (56.4%) and death with dignity (63.7%) decreased. In a comparison of death with dignity and life with dignity, the number of nephrologists who support life with dignity (47.1%) was greater than that supporting death with dignity (15.9%).
Our results suggested that death with dignity may be performed when there is an AD and both the nephrologist and the family respect the patient's self-determination. Furthermore, many nephrologists consider that either AD or death with dignity is required. While, it is supposed that life with dignity is very important for human being, nephrologists were more supportive of life with dignity than death with dignity. Since the right-to-life of all Japanese citizens is guaranteed by the Constitution of Japan, we can start to live with dignity at the terminal stage. Thus, we should recognize that AD for life with dignity is the most important for self-determination within the social consensus.

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We examined the effect of body mass index (BMI) in patients undergoing chronic hemodialysis (HD) on the three-year mortality. The three-year mortality rate of outpatients undergoing chronic HD (n=258; 144men) was determined. BMI was examined at the beginning of this study. Two male patients were excluded due to BMI alteration greater than 1 during the study period. Patients were subdivided according to undergoing gender, age (below 60 or more than 60 years old), dialysis duration below 5 years or more than 5 years the primary disease, and the stability of dialysis. In patients under 60 years of age, the mortality rate was lowest at a BMI of approximately 20, regardless of gender, HD duration and HD control. However, a lower BMI was associated with a greater mortality rate in patients 60 years old or older. Patients under 60 years of age, relative risk of mortality was affected by BMI, primary disease (diabetes mellitus) and stability of HD. For the older patients group, the relative risk of mortality was influenced by BMI and the age (the older, the worse). The implications of BMI on the results of HD should be considered separately for younger and older patients.

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Reagents have recently been developed for the measurement of glycated albumin (GA) based on an enzymatic method. For diabetic patients not on hemodialysis, a high correlation has been demonstrated between the GA values obtained with the enzymatic method and the values obtained with the traditional HPLC method, indicating that the enzymatic method can be substituted for the HPLC method.
We examined whether this enzymatic method could also replace the traditional HPLC method for diabetic patients on hemodialysis. In 165 diabetic patients on hemodialysis, the values obtained by the enzymatic method showed a good correlation with those values generated by the HPLC method (r=0.987). The enzymatic method for GA was also shown to be useful in patients with hypoproteinemia (TP<6.0g/dL) and patients with hypoalbuminemia (Alb<3.5g/dL) as well as patients with severe azotemia.

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Heparin-induced thrombocytopenia (HIT) is a relatively common antibody-mediated drug reaction, but is underestimated as a limb- or life-threatening complication induced by heparin. Here, we report a 69-year-old diabetic man who developed HIT and he was complicated by repeated episodes of clotting in the dialyzer and extracorporeal circuit during hemodialysis (HD). He had been treated 2 times a week with unfractionated heparin. Unexpected clot formation in the dialyzer was observed with a decreased platelet count from 19.8×10⁴/mm³ (day 1) to a nadir of 9.7×10⁴/mm³ (day 14). Each dialysis session required saline or heparinized saline flushes to prevent clotting, while frequent change of the dialyzer was needed. Clotting episodes were observed even after changing the dialyzer membrane and/or anticoagulant agents (nafamostat mesilate or low molecular weight heparin). He developed thrombophlebitis after fundal gastrectomy for early gastric cancer when treated with nafamostat mesilate. A diagnosis of HIT was subsequently confirmed with a positive platelet factor 4-heparin antibody (ELISA assay). Currently, the combined therapy of nafamostat mesilate with oral anticoagulant treatment with warfarin has been used effective for preventing clotting episodes during HD. The HIT management will be achieved with the discontinuation of all forms of heparin exposure and the institution of anticoagulation with an alternative agent. Currently, the direct thrombin inhibitor, argatroban is considered to be best for treatment of HIT, but it is not approved in Japan. We have no choice other than the institution of nafamostat mesilate in conjunction with anti-platelet drugs or warfarin. Since patients on HD are repeatedly exposed to heparin, one might expect a higher frequency of HIT. However, the recognition and treatment of patients with HIT is still unsatisfactory. The prevention of this severe complication should be considered as an important goal especially in HD patients.

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We found frequent clot formation in extracorporeal circulation in a 83-year-old man after the start of hemodialysis treatment, and the severe thrombocytopenia progressed from 17.8×10⁴/mm³ before starting hemodialysis to 1.6×10⁴/mm³ after the sixth hemodialysis treatment. We started constant infusion of heparin sodium because this condition was considered due to DIC and there was coexisting thrombotic stenosis in the shunt run-off vein. Thereafter, deep venous thrombosis, shunt obstruction, and pulmonary embolism occurred. As a result of positive findings on platelet aggregation test, we diagnosed heparin-induced thrombocytopenia and stopped heparin. Thereafter, the platelet count soon recovered and anti-PF4/heparin antibody was also determined. Thrombotic condition persisted, even after withdrawal of heparin, but it was improved by administering an anti-thrombin agent, argatroban. In this case, there were various allergic episodes including drug allergy to antibiotics, eosinophilia after starting CAPD, and newly appearing multiple irregular antibodies. Although the mechanism of HIT antibody production remains unclear, some immunological abnormalities, including allergy might be involved. To elucidate HIT risk factors, further accumulation and analysis of many cases appears necessary.

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A 42-year-old woman was admitted to our hospital for initiation of hemodialysis (HD) on January 1990. On admission, serum total protein level was 14.4g/dL, serum γ-globulin level was 62.5%, serum immunoglobulin G level was 9, 650mg/dL, and serum calcium level was 7.6mg/dL. The diagnosis of immunoglobulin G-κ type multiple myeloma was based on the findings of plasma cell proliferation in bone marrow aspirate the presence of immunoglobulin G-κ type M protein and Bence-Jones protein on serum and urine immunoelectrophoresis tests, respectively. We performed double-filtration plasmapheresis eight times and administered 13 cycles of melphalan and prednisolone therapy. During the last 12 years, the serum total protein level of this patient has remained below 8g/dL, and the percentage of the serum γ-globulin level has remained below 50% of the serum total protein level.
Many studies have reported that multiple myeloma patients requiring HD have a poor prognosis. However, our patient survived for a long time; DFPP and MP therapy administered soon after diagnosis seem to be effective, inhibiting the activity of multiple myeloma; furthermore, the patient had not developed any severe infection or sepsis during the chemotherapy.

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Maxacalcitol therapy was applyed for treatment of secondary hyperparathyroidism associated with an intact parathyroid hormone (intact-PTH) level higher than 500pg/mL in three patients on peritoneal dialysis. The patients were one male and two females aged 51.3 years on average. The mean duration of dialysis was 5.7 years and all patients had been maintained on CAPD alone. Intravenous administration of maxacalcitol was initiated with a single dose of 10μg weekly. When the intact-PTH level failed to decrease, the dose was increased gradually to a maximum dose of 30μg by 10μg per week, and then was adjusted to maintain the intact-PTH level between 100pg/mL and 250pg/mL. The intact-PTH level decreased in all patients. Levels of osteocalcin and bone alkaline phosphatase, a bone formation marker, also decreased. However, maxacalcitol therapy was discontinued in one patient who showed an increased intact-PTH level after the dose of the drug was reduced due to hypercalcemia, and in another patient who developed an increase of CPK in association with neurological symptoms of numbness. As reported above, treatment with maxacalcitol was effective in controlling secondary hyperparathyroidism in CAPD patients, but it is necessary to pay careful attention to adverse reactions such as an increase in CPK especially after reduction of dose.

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[in Japanese]

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