Atsuo Takemasa

Serum soluble interleukin-2 receptor in patients with glomerulonephritis

Serum soluble interleukin-2 receptor (IL-2R) concentrations were determined using the ELISA method in 55 cases of glomerulonephritis. These patients can be classified as 29 cases of IgA nephropathy, 10 cases of membranous glomerulonephritis and 16 cases of mesangial proliferative glomerulonephritis. Our results showed that serum soluble IL-2R concentrations in glomerulonephritis cases were significantly higher than those in healthy controls. Among the different types of glomerulonephritis cases, however, no significant differences in serum soluble IL-2R were observed. While we found a significant positive correlation of serum soluble IL-2R to BUN and creatinine, we also found a significant negative correlation between serum soluble IL-2R and creatinine clearance. These findings suggest that serum soluble IL-2R can serve as an indicator of exacerbation of glomerulonephritis.

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage N. Noriaki Yorioka H. Hiroaki Oda T. Takahiko Ogawa Y. Yoshihiko Taniguchi S. Shigeyuki Kushihata A. Atsuo Takemasa K. Koji Usui K. Kenichiro Shigemoto S. Satoru Harada M. Michio Yamakido 2nd Department of Internal Medicine, Hiroshima University School of Medicine, and Ichiyokai Harada Hospital, Hiroshima, Japan

Stimulation of Tumour Necrosis Factor-alpha Production by Recombinant Human Erythropoietin may Contribute to Failure of Therapy

Although the mechanism of unresponsiveness to recombinant human erythropoietin therapy in dialysis patients has been studied extensively in recent years, many aspects remain unclear. We previously found that administration of erythropoietin induces interleukin-1beta, a cytokine that inhibits erythropoiesis. The present study investigated the involvement of tumour necrosis factor-alpha, another cytokine which inhibits erythropoiesis. Peripheral blood mononuclear cells were obtained from 18 patients on continuous ambulatory peritoneal dialysis, who were being treated with erythropoietin for renal anaemia, and were cultured with various concentrations of erythropoietin (0, 1, 5, 10, and 50 U/ml). Then the tumour necrosis factor-alpha level in the culture supernatant was assayed. The 18 patients were divided into four groups on the basis of the haematocrit after treatment: group A (n = 3), <23.0%; group B (n = 5), 23.0-24.9%; group C (n = 7), 25.0-26.9%; and group D (n = 3), > or =27.0%. In group A, the tumour necrosis factor-alpha level in the culture supernatant was increased by incubation with erythropoietin, while it was not increased in other groups. The tumour necrosis factor-alpha level was significantly higher in group A than in the other groups at erythropoietin concentrations of 5 U/ml. These results suggested that induction of tumour necrosis factor-alpha is one of the reasons for unresponsiveness to recombinant human erythropoietin.

Investigation of the influenza-like symptoms associated with recombinant human erythropoietin therapy

The mechanism by which fever and influenza-like symptoms occur, after the administration of recombinant human erythropoietin (rHuEPO) to patients on continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood mononuclear cells, obtained from two patients with fever and/or influenza-like symptoms related to the administration of rHuEPO for the treatment of anaemia were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of interleukin-1 β and tumour necrosis factor-α was higher in cultures with rHuEPO than in cultures without rHuEPO, although the dose relationships were not clear. These findings suggest that increased production of interleukin-1 β and tumour necrosis factor-α, induced by administration of rHuEPO, may cause fever and influenza-like smptoms.

Stimulation of interleukin-1 beta production may be involved in unresponsiveness to erythropoietin therapy.

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1ß, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 ß production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 ß during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 ß, and there was a significant difference between the two groups. Induction of IL-1 ß by rHuEPO may be one cause of persistent anemia in dialysis patients.

Mechanism of Increased Serum Soluble Interleukin-2 Receptor Levels in Patients on Continuous Ambulatory Peritoneal Dialysis

Objective: The aim of this study was to investigate the mechanism underlying the increase of serum soluble interleukin-2 receptor (IL-2R) levels in patients on continuous ambulatory peritoneal dialysis. Material and Methods: In 13 dialysis patients and 17 healthy controls, serum soluble IL-2R levels were determined by enzyme-linked immunosorbent assay, and CD25-positive (cell surface IL-2R-positive) cells were detected by flow cytometry. Soluble IL-2R levels were also measured in the supernatant of cultured peripheral blood mononuclear cells. Results: The serum soluble IL-2R level was significantly higher in the patients than in the healthy controls (pOBJECTIVE The aim of this study was to investigate the mechanism underlying the increase of serum soluble interleukin-2 receptor (IL-2R) levels in patients on continuous ambulatory peritoneal dialysis. MATERIAL AND METHODS In 13 dialysis patients and 17 healthy controls, serum soluble IL-2R levels were determined by enzyme-linked immunosorbent assay, and CD25-positive (cell surface IL-2R-positive) cells were detected by flow cytometry. Soluble IL-2R levels were also measured in the supernatant of cultured peripheral blood mononuclear cells. RESULTS The serum soluble IL-2R level was significantly higher in the patients than in the healthy controls (p < 0.0001). In contrast, both the percentage and the absolute count of CD25-positive cells showed no significant differences, and neither did the soluble IL-2R level in culture supernatant. Serum soluble IL-2R levels showed a positive correlation with the serum beta2-microglobulin level (p < 0.01), the age of the patients (p < 0.05), and duration of dialysis (p < 0.05), as well as a negative correlation with the urine volume (p < 0.05). CONCLUSIONS The increase of serum soluble IL-2R in patients on peritoneal dialysis may be caused by accumulation due to its low transperitoneal clearance and low urinary excretion.

Dose Escalation Induces Tolerance to Side-Effects of Erythropoietin in a Patient with Dialysis Anaemia: Case Report

A 51-year-old woman began haemodialysis for chronic renal failure in February 1981. Symptomatic anaemia required treatment with recombinant human erythropoietin (rHuEPO) in February 1990 (3000 IU, twice weekly, intravenously). She developed influenza-like symptoms and treatment was withdrawn. In June 1994 rHuEPO was resumed at a very low dose of 100 IU subcutaneously three times weekly, and was increased gradually to 500 IU, without inducing any side-effects. At this dose the haematocrit was maintained at 22.0 – 25.0% and the symptoms of anaemia improved. In patients like ours, with influenza-like symptoms caused by rHuEPO therapy, dose escalation starting from an ultra-low dose may be effective in avoiding side-effects.

Measurement of bone mass by microdensitometry in patients undergoing hemodialysis.

慢性血液透析患者 (HD患者) の腎性骨異栄養症 (ROD) の詳細を知る目的にて慢性血液透析患者88例 (男性59例, 女性29例), 健常者60例 (男性30例, 女性30例) においてmicrodensitometry法を用いて骨量を測定した. 更には得られた骨量と臨床的諸因子, 治療との関連性について多変量解析により検討した. その結果, 1. 40歳代のHD患者では同年代の健常者に比しMCIの有意な低下が認められた. 2. MCIの低下に寄与すると考えられる項目は, 年齢60歳以上, 透析期間61か月以上, オステオカルシン10.1ng/ml以上, 血清カルシウム5.0mEq/l以下, 抗リン剤としてアルミゲル, 炭酸カルシウム単独投与等であった. 3. 30-50歳代のHD患者では同年代の健常者に比しΣGS/Dの有意な低下が認められた. 4. ΣGS/Dの低下に寄与すると考えられる項目は, 透析期間61か月以上, 年齢40歳以上, 性別女性, フェリチン251ng/ml以上, オステオカルシン10.1ng/ml以上, C-PTH 3.1ng/ml以上等であった. 以上より, RODの進展防止にはMD法による骨量指標と共に各種臨床的諸因子を総合的に判断し, 少なくとも適切なる抗リン剤, ビタミンD3の投与が重要であると考えられた.