Hiroaki Asada

Efficient Removal of Albumin-Bound Furancarboxylic Acid by Protein-Leaking Hemodialysis

Furancarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, CMPF), an inhibitor of erythropoiesis, cannot be removed by conventional hemodialysis due to its strong albumin binding, resulting in its accumulation in uremic serum. We used protein-leaking hemodialysis with BK-F dialyzers in 8 uremic patients for 4 months to determine its effect on the serum levels of CMPF. Pre-hemodialysis serum levels of CMPF significantly decreased to about 50% after 4 months by protein-leaking hemodialysis, while those of BUN and serum creatinine did not change significantly. Pre-hemodialysis hematocrit and hemoglobin levels significantly increased by protein-leaking hemodialysis. These results indicate that protein-leaking hemodialysis reduces serum levels of albumin-bound CMPF and improves anemia.

Profiling of uremic ultrafiltrate using high resolution gas chromatography-mass spectrometry - identification of 6 polyphenols.

An analytical method for separation and identification of compounds in uremic ultrafiltrate has been developed using a glass capillary column gas chromatography-mass spectrometry-computer system. The ultrafiltrate samples of blood were obtained during hemodialysis treatment of chronic uremic patients and non-uremic patients using the extracorporeal ultrafiltration method. Sample preparation consisted of acidification, extraction, evaporation, and trimethylsilylation. Many compounds were newly identified in the uremic ultrafiltrate by electron impact ionization, chemical ionization, and high resolution mass spectrometry. Six toxic polyphenols, namely, catechol, resorcinol, hydroquinone, 2-methoxyresorcinol, 3-methoxycatechol, and methoxyhydroquinone were first detected in the uremic ultrafiltrate.

Gas chromatographic-mass spectrometric analysis of organic acids in renal tissue biopsy: identification of 4-hydroxybutyric acid and 4-hydroxy-2-butenoic acid.

The organic acids in renal tissue biopsy (0.5-1 mg) obtained from chronic glomerulonephritis patients were analyzed capillary column gas chromatography--mass spectrometry. Some twenty compounds were identified in the renal tissue. The organic acid profile of renal tissue showed a marked difference from those of urine and serum. In particular, 4-hydroxybutyric acid and 4-hydroxy-2-butenoic acid, which are usually undetectable in urine and serum, were detected for the first time in renal tissue in considerably large amounts.

Profiling of organic acids and polyols in nerves of uraemic and non-uraemic patients.

Organic acids, polyols and lipid-bound polyols in the cauda equina nerves of uraemic patients and non-uraemic patients were analysed with high-resolution gas chromatography-mass spectrometry. In the uraemic nervous tissue, the concentrations of myoinositol and 4-hydroxyphenylacetic acid were increased. Levulinic acid was first detected in the nervous tissue as a normal component. 1-Deoxyglucose and free and lipid phosphatide scylloinositol were detected in the nervous tissue as normal components.

Prostaglandin E1 infusion therapy in chronic glomerulonephritis--a double-blind, crossover trial.

Nine patients with chronic glomerulonephritis were investigated in a controlled, double-blind, crossover study to assess the efficacy of prostaglandin E1 (PGE1) infusion therapy. Three-hour intravenous infusions of PGE1 (100 micrograms/day) and placebo were performed every day for three weeks, respectively. Improvement of renal function was demonstrated by statistical u-test (p less than 0.01) and x2-test (p less than 0.05). Three weeks infusion of PGE1 tended to increase creatinine clearance. PGE1 infusion significantly decreased the serum level of creatinine as compared with the placebo infusion (p less than 0.05). The urinary excretion of protein, however, did not change with PGE1. It was concluded that PGE1 infusion is effective in improving renal function in patients with chronic glomerulonephritis.

Ischemic change of organic acids in kidney.

Organic acids in rabbit renal tissue biopsy were analyzed by capillary column gas chromatography--mas s spectrometry. The change of these organic acids under ischemic conditions was determined over 60 min after clamping the renal artery and vein. The results showed that lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxypropionic acid, 2-methyl-glyceric acid, glyceric acid and malic acid increased at 4 and 6 min after clamping, but then decreased at 15 min. Glycerol increased 2 min after clamping and then decreased. However, 3-deoxyaldonic acids of 3-deoxytetronic acid, 3-deoxy-2-C-hydroxymethyltetronic acid and 3-deoxypentonic acid decreased in the renal tissue biopsy from 2 min after clamping.

A retrospective study on the outcomes of MPO-ANCA-associated vasculitis in dialysis-dependent patients

Objectives. This study investigated the clinical course of myeloperoxidase-antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after starting dialysis. Methods. A retrospective review was conducted of the clinical charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who attended one of 8 associated clinics over the past 21 years. Results. Eighty-nine patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1 had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal-limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency, 0.05 relapses/person-year; 95% confidence interval, 0.03–0.08). Mean time from start of dialysis to relapse was 65 ± 59 months. Cox multivariate analysis showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR], 21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and cyclophosphamide use (HR, 0.20) were significant predictors of mortality. Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively; infection was the most frequent cause of death. Conclusion. Pulmonary involvement was a predictor of relapse and mortality. Although relapse can occur long after the start of dialysis, incidence was low among dialysis-dependent patients. Prolonged maintenance immunosuppressive therapy might be limited to patients with pulmonary involvement in dialysis-dependent ANCA-associated vasculitis.