It has recently been found that hypoparathyroidism (Hypo), an insufficient secretion of parathyroid hormone (PTH) resulting in decreased normal bone turnover, appears with great frequency in hemodialysis patients. However, the long-running controversy about the clinical significance of Hypo has not yet been clarified. We grouped 92 patients treated at a single dialysis unit from 1989 to 1995 into four categories [absolute Hypo, intact (I) PTH<60pg/ml; relative Hypo, 60≤I-PTH<160; Normal, 160≤I-PTH<300; Hyper, 300≤I-PTH], and we investigated the incidence and progress of Hypo and whether Hypo affected the bone mineral density from the 2nd to 4th lumbar (L_2-4BMD). The frequency of absolute Hypo decreased from 57.6% in 1989 to 23.9% in 1995 (p<0.001), and the sum of absolute and relative Hypo also decreased from 80.4% to 62.0% over the same period (p<0.01). Among the 53 cases of absolute Hypo in 1989, 32 cases shifted to the higher I-PTH categories, 3 cases shifted to Normal, and 5 cases shifted to Hyper. The calcium concentration of dialysate was unchanged in each category throughout the period, and there were no changes of serum calcium and phosphonate. The mean dosage of prescribed CaCO₃ increased from 3.2g/day to 3.5g/day from 1989 to 1995, but statistical significance was not achieved. The mean dosage of prescribed alfacalcidol decreased from 0.30μg/day to 0.16μg/day (p<0.0001). L_2-4BMD was 0.93±0.15g/cm² in 1989, and 0.94±0.19g/cm² in 1995 (P:NS). In 17 cases who remained in the absolute Hypo category throughout the study period, L_2-4BMD increased by +3.7%. The frequency of absolute Hypo decreased in our dialysis unit from 1989 to 1995, and we observed a 60.4% improvement in PTH secretion in absolute Hypo cases over the same period, with decreases in the alfacalcidol dosages. We surmised that the appearance of Hypo might be related to the alfacalcidol administration. On the other hand, absolute Hypo maintained throughout the five-year period did not affect L_2-4BMD.

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To elucidate whether or not the improvement of anemia with the resultant hyperviscosity is one of the causes of rHuEPO-derived hypertension, the present study was conducted with 29 hemodialysis patients and 15 predialysis patients. They were kept in the supine position for 60 minutes (min) before the study and for 60 min during the study. Measurement of blood pressure was done every 30 min and blood samples were obtained before and after the study. Circulating blood cells (CBC), pressor substances such as plasma catecholamines (NA, A), plasma aldosterone concentrations (PAC), plasma renin activity (PRA) and plasma endothelin-1 (ET-1) were assayed. The amount of rHuEPO (Epoetin-β) given intravenously was 3000 units to dialysis patients and 6000 units to predialysis patients. CBC did not change over the 60 min study in either group. In contrast, blood pressure varied from 142.7/76.5mmHg to 145.1/78.6mmHg at 30 min and rose to 150.9 (p<0.05)/79.5mmHg at 60 min in the dialysis patients. Likewise, blood pressure increased from 139.5/74.8mmHg to 147.5/83.2 (p<0.05) mmHg at 30 min and 154.3/85.1mmHg (p<0.005) at 60 min in the predialysis patients. Mean blood pressure increased significantly at 60 min in predialysis patients (p<0.005). Additionally, ET-1 significantly increased from 15.4±3.5pg/ml to 18.1±4.2pg/ml in dialysis patients (p<0.05) and from 13.7±4.3pg/ml to 16.0±4.7pg/ml in predialysis patients (p<0.05). These elevations may be attributed to the increased generation of ET-1 by rHuEPO. A significant elevation of pressor substances (NA, A, PAC and PRA) was not detected. In conclusion, rHuEPO or ET-1 may be one reason for elevated blood pressure.

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To investigate a new alarm system for early detection of a sudden drop of blood pressure while removing water during hemodialysis, we measured the arterial-venous pressure difference in the blood circuit (AV-pressure difference) and continuous Ht (CLM-Ht) using a non invasive optical technique (CRIT-LINE monitor) for measuring hematocrit.
The relation between both values and systolic blood pressure (SBP) were discussed in 12 cases. 1) Significant negative correlation was found among the rate of AV-pressure difference, rate of CLM-Ht and systolic blood pressure (SBP) in all groups. 2) We could prevent the blood pressure from suddenly dropping during hemodialysis by monitoring the rise in the rate of A-V pressure difference and CLM-Ht below+20%.
Therefore, it seems to be useful to monitor the AV-pressure difference and CLM-Ht in clinical practice.

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To evaluate improvement in sexual functions after renal transplantation, we conducted a questionarre survey regarding this issue. Fifty-seven patients who had undergone renal transplantation in our hospital were evaluated. Hormonal profiles (LH, FSH, PRL, T, free T) of 42 patients were also analyzed after informed consent was obtained.
Frequency of coitus was lower among hemodialysis patients compared with that among normal control and there was no significant improvement observed after renal transplantation, although hormonal profiles of renal transplants became very similar to those of normal control. (LH: 6.2±3.8mIU/ml, FSH: 9.9±6.6mIU/ml, PRL: 5.9±2.9ng/ml, T: 390±110ng/dl, free T: 16.5±5.3pg/ml). Serum creatinine, immunosuppressants, duration of hemodialysis and hormonal profile were evaluated between two patients groups with or without improvement of sexual function after renal transplantation, but there was no significant difference observed. Of 9 impotent cases, 6 patients who had undergone transplantation before 40 years of age, became potent after renal transplantation.
Factors other than hormones might be important for sexual functions of patients receiving hemodialysis and the importance of transplantation at a younger age is suggested.

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We evaluated the passage of endotoxin (ET), beta-glucan (BG), and peptidoglycan (PG) across high flux membrane dialyzers using tap water as a test solution. We tested cellulose tri-acetate (FBF, Nipro), polymethylmethacrylate (BKF, Toray), and polysulfone (PSN, Kawasumi, and APS, Asahi) high-flux membrane (HFM) dialyzers in this study. Conventional regenerated cellulose membrane (RCM) dialyzer served as a control. The experimental design used a recirculating batch system for 120 minutes. Endotoxin-free 0.05% albumin containing distilled water solution was circulated as the blood compartment and tap water was circulated as dialysate compartment. Samples were estimated by endotoxin specific test (ES) for ET, high sensitive test (HS) for ET and BG, and silkworm larvae plasma test (SLP) for BG and PG with Toxinometer MT-358 (Wako) supplied by Wako Pure Chemical industries Ltd. (Osaka). ES activity was high in the dialysate compartment, but not detectable in the blood compartment by all HFM dialyzers and the RCM dialyzer. HS activity was detectable in the blood compartment, but decreased in the dialysate compartment by all HFM dialyzers and the RCM dialyzer. The blood compartment in the RCM dialyzer showed the highest HS activity among PSN, BKF, FBF and APS. SLP activity was high in the blood compartment and dialysate compartment by all HFM dialyzers and the RCM dialyzer. The blood compartment in the RCM dialyzer showed the highest SLP activity among PSN, FBF, APS and BKF. These data showed, that ET did not pass through HFM, but adsorbed to membrane surface of HFM. BG may have passed through the HFM dialyzer. The RCM dialyzer eluted BG derived from cellulose material which might stimulate SLP activity. This study also indicated that tap water was useful for evaluating passage of SLP activating substances across HFM dialyzers.

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We investigated the pharmacokinetics of fleroxacin (FLRX), a new quinolone, after a single oral administration of FLRX 100mg tablet in five maintenance hemodialysis patients. The serum concentrations of FLRX reached a peak of 1.87μg/ml at 2.4h after the administration. The half-life in serum was 6.62h during hemodialysis, being reduced from 31.9h without hemodialysis. The dialysis clearance (69 to 74ml/min) was comparable to renal clearance in healthy subjects. Twenty-eight percent of the drug was removed from the body during a 4-hour hemodialysis session. These results suggested that in hemodialysis patients the half-life in serum was more prolonged by 3 times that in healthy subjects, and that FLRX might be moderately dialyzed. Then, the serum concentration profiles of FLRX during multiple dosing were simulated based on the single-dose pharmacokinetic parameters. We concluded that it might be appropriate to administer FLRX at a dose of 100 mg once daily in these patients.

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We report two dialysis patients with the early onset of pancytopenia related to low-dose weekly pulse methotrexate (MTX) with rheumatoid arthritis.
Case 1: A 46-year-old woman on maintenance hemodialysis for 15 years was admitted because of genital bleeding, severe mucositis and fever. Two weeks before admission she began to receive 5.0mg of MTX a week for RA. On admission, her white blood cell (WBC) count was 200/μl with 2% neutrophils, 20% eosinophils, 0% basophils, 0% basophils, 73% lymphocytes and 0% monocytes. Hemoglobin was 3.8g/dl and the platelet count was 35, 000/μl. She was treated with granulocyte colony stimulating factor (G-CSF), antibiotics, and platelet and red blood cell transfusions. Peripheral blood recovery was apparent by the 12th day after admission. MTX has not been restarted.
Case 2: A 49-year-old woman on maintenance hemodialysis for 9 months was admitted because of treatment for RA. She had previously received prednisolone (10mg/day) and diclofenac sodium (50mg/day). These drugs were not very effective for joint swelling and tenderness, so she started taking 2.5mg of MTX a week. On the 10th day after administration of MTX, she developed severe mucositis and fever. On the 15th day, her WBC count was 300/μl with 0% neutrophils, 30% eosinophils, 1% basophils, 69% lymphocytes and 0% monocytes. Hemoglobin was 5.8 g/dl and the platelet count was 13, 000/μl. She was treated with G-CSF, antibiotics, and leucovorin and platelet transfusions. Peripheral blood recovery was apparent by the 19th day after the second administration of MTX. MTX has not been restarted.
Low-dose pulse MTX therapy is effective for RA. Pancytopenia resulting from this therapy has been reported in patients with impaired renal function, advanced age, decreased serum albumin and concurrent ingestion of nonsteroidal anti-inflammatory drugs. We recommend that dialysis patients avoid low-dose MTX, since MTX is poorly removed by hemodialysis and the patients show an allergic reaction to MTX.

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