Percutaneous calcitriol injection therapy (PCIT) for secondary hyperparathyroidism: multicentre trial.

A multicentre trial of percutaneous calcitriol injection therapy (PCIT) was designed to evaluate its clinical usefulness. During a 12-week period, measurement of intact PTH concentration, and other parameters, and ultrasonography were carried out in conjunction with PCIT in 19 haemodialysis patients with secondary hyperparathyroidism and enlarged parathyroid glands (PTGs) that were resistant to vitamin D pulse therapy. Calcijex was injected directly into the PTG three times per week on the patient's non-dialysis days: eight patients received a 2 microg/ml preparation (group A) and 12 received 1 microg/ml (group B). A strong clinical effect was observed in group A compared with group B, which suggests that the effect of calcitriol by direct injection is stronger when there is a higher concentration of calcitriol in the PTG. In group B, the cases with an initial intact PTH concentration <1000 pg/ml and a single enlarged PTG had a good response to the treatment. Concentrations of calcium and phosphate were not significantly changed in either group. All cases had decreased blood flow in the PTG after three episodes of PCIT and, although the size of the PTG was unchanged, or even a little increased, immediately after the treatment, it decreased gradually over 2-6 weeks. PCIT may be effective for comparatively slight secondary hyperparathyroidism, but further investigation is necessary because there were comparatively few cases.

Plasma exchange for acquired hemophilia: a case report.

A patient with acquired hemophilia complicated with chronic renal failure and lung tuberculosis was successfully treated by consecutive plasma exchange (PE). A 71-year-old man with serious bleeding tendency showed low coagulation factor levels and a high titer of factor VIII (FVIII) inhibitor, and he was diagnosed with acquired hemophilia. Because of the complication of active lung tuberculosis, instead of immunosuppressive therapy, he undertook a series of PE with fresh frozen plasma replacement for 3 months. After the start of PE, his bleeding symptoms and activated partial thromboplastin time (APTT) improved gradually according to the decrease in FVIII inhibitor levels. These results suggest that PE is an effective therapeutic tool for refractory acquired hemophilia.

Plasma exchange for thrombocytopenia in antiphospholipid syndrome: a case report.

The remarkable effect of plasma exchange (PE) was observed on thrombocytopenia in a patient with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus. Three times PE led to recovery from severe thrombocytopenia refractory to treatment with corticosteroid, anticoagulant, and antiplatelet drugs accompanied by a decrease in the serum cardiolipin beta2 glycoprotein I antibody level. This result suggests that PE is a valuable therapeutic tool for refractory thrombocytopenia in APS.

rHuEPO enhances the production of plasminogen activator inhibitor-1 in cultured endothelial cells.

The direct effects of recombinant human erythropoietin(rHuEPO) on coagulation and fibrinolysis factors were evaluated in a cultured endothelial cell (EC) system. Confluent quiescent ECs were incubated with or without 5.0 U/ml rHuEPO for 1, 6, and 18 hours, and supernatant concentrations of plasminogen activator inhibitor-1 (PAI-1): antigen (Ag), tissue plasminogen activator and thrombomodulin, and supernatant activities of tissue factor pathway inhibitor and von Willebrand factor were measured. The results showed that only PAI-1 levels were increased by the presence of rHuEPO. In order to assess the effect of rHuEPO on PAI-1 production by EC more precisely, confluent ECs were incubated with various doses of rHuEPO (0, 1.0, 2.5, 5.0, 10.0 U/ml) for 1, 6, 12, and 18 hours, and PAI-1:Ag concentrations in the supernatants of media were measured. PAI-1:Ag in the supernatants were increased by the presence of rHuEPO at all incubation times (P < 0.01) and the increase in PAI-1:Ag was dependent on rHuEPO concentration. The increases in PAI-1:Ag by 5.0 U/ml rHuEPO were comparable to those by 0.1 U/ml tumor necrosis factor-alpha, 1.0 microgram/ml lipopolysaccharide, and 0.5 U/ml thrombin. The increase in PAI-1:Ag by rHuEPO was suppressed by pre-incubation with 10 micrograms/ml cycloheximide (P < 0.01) or 0.2 microgram/ml actinomycin D (P < 0.01). These results indicate that rHuEPO directly stimulates PAI-1 production in cultured EC via de novo protein and RNA syntheses.

Dialysis membranes in the year 2000: performance and biocompatibility.

Among many substances accumulated or generated by renal failure, much attention has focused on the pathogenetic effects of advanced glycation end-product (AGE)-bound proteins such as AGE-modified beta 2-microglobulin, and bioactive substances such as inflammatory cytokines. In order to remove these substances efficiently, dialysis membranes in the year 2000 should have a higher molecular cut-off point and a sharper cut-off curve, with less formation of concentration polarization, or a greater adsorbing capacity for target substances with less ensuing protein gel layer. Adequate supplementations for depleted substances by more efficient dialysis will be necessary as at present with carnitine and vitamins. Further, from now until the year 2000, membranes in which biocompatibility nearly corresponds to that of capillary endothelium, and safe and economical purification systems of dialysate should be realized.

Relative hypoparathyroidism in hemodialysis patients.

To clarify the incidence and contributing factors of hypoparathyroidism in a hemodialysis (HD) population, 224 patients undergoing maintenance HD were investigated. They were divided into 4 groups according to their high-sensitive parathyroid hormone levels: extra-high (EH) group > 420,000 pg/ml; high (H) group 20,000-420,000 pg/ml; moderate (M) group 4,500-20,000 pg/ml; low (L) group, < 4,500 pg/ml. In group L, a 25-mg/kg deferoxamine (DFO) infusion test was undertaken to estimate aluminum (Al) accumulation. The distribution in each group was 42, 35, 12, and 11% for groups L, M, H and EH, respectively. Group-L patients were relatively older than those of the other groups. Diabetes was seen in 20% of group-L patients, as opposed to no diabetes in groups H and EH. Among the 22 diabetics, 82% were in group L. 70% of group-L patients showed a less than 50-micrograms/l Al increment after the DFO infusion test. Bone mineral density (BMD) did not differ between the groups with relative hypoparathyroidism (RHP=L) and background-matched non-RHP, either at the initiation of HD or the recent period, and the changes in BMD were comparable between the 2 groups. These results suggest that a considerable number of HD patients show RHP. Diabetes, but not Al accumulation, was considered to be one of the predisposing factors of RHP. Though the outcome of RHP will be aplastic bone disease (ABD) in HD patients, the clinical significance of ABD has not been fully evaluated. Further studies are required to clarify the precise mechanisms of RHP and the significance of ABD.

Effect of dialysis membranes and ACE inhibitor on bradykinin levels during hemodialysis.

The effects of dialyzer membrane material and concurrent angiotensin converting enzyme (ACE) inhibitor on plasma bradykinin levels during hemodialysis were investigated. Six patients treated with an ACE inhibitor and 6 other patients not receiving an ACE inhibitor underwent three consecutive hemodialysis sessions with an AN-69 dialyzer and three sessions with a polysulfone dialyzer. The sequence of dialyzers (AN-69 followed by polysulfone or the reverse) was determined randomly. With the AN-69 membrane dialyzer, the plasma bradykinin level at the dialyzer outlet was significantly greater than that at the dialyzer inlet at 5 min but not at 10 min after initiation of dialysis, whereas no significant difference between inlet and outlet bradykinin concentrations was observed at either time with the polysulfone membrane dialyzer. The changes in plasma bradykinin level in patients with concurrent ACE inhibitor did not differ from those found in patients without ACE inhibitor. These results indicate that the AN-69 membrane stimulates bradykinin production at the initial stage of hemodialysis in patients with as well as without concurrent ACE inhibitor. Further study is necessary to clarify the exact role of ACE inhibitor in elevation of bradykinin levels during hemodialysis.