| Co-Investigator(Kenkyū-buntansha) |
MOROZUMI Makoto Saitama Medical Center, Saitama Medical School, Associate Professor, 総合医療センター, 助教授 (60166460)
UCHIDA Atsushi University of the Ryukyus, University Hospital, Assistant Professor, 医学部附属病院, 講師 (80245571)
HOKAMA Sanehiro University of the Ryukyus, Faculty of Medicine, Instructor, 医学部, 助手 (20229157)
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| Budget Amount *help |
¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2005: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2004: ¥43,160,000 (Direct Cost: ¥33,200,000、Indirect Cost: ¥9,960,000)
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| Research Abstract |
Oxalate is a uremic toxin, that can be deposited in the tissues and organs of long-term hemodialysis patients. Arteriosclerosis develops early in these patients and is associated with a high risk of hypertension, coronary artery disease, and cerebrovascular disease. Hyperoxalemia damages the vascular endothelium, giving rise to arteriosclerosis. Patients also suffer from carboxyl stress because of their uremic state, and administration of ascorbate may improve this redox condition and may also be beneficial for various vicious cycles, e.g., that leading to cancer. High doses of ascorbate, however, cause hyperoxalemia in dialysis patients and potentially lead to the onset of oxalosis.
1.Capillary electrophoresis for measurement of serum oxalate was first introduced to our laboratory about 6 years ago. Measurement of serum oxalate-related substances in 452 hemodialysis patients showed that the serum oxalate level was strongly associated with serum ascorbate, suggesting that ascorbate inta
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ke may influence serum oxalate. Vitamin C administration improves iron utilization and may be useful for erythropoietin-refractory anemia in dialysis patients. It has also been suggested that vitamin C administration may reduce the erythropoietin dose. To balance the benefit and risks, the does of vitamin C should be limited to around 100 mg per day. Calcium phosphate is deposited in the tissues of dialysis patients, who may also suffer from calcium oxalate deposition when the serum oxalate level exceeds 100 μmol/l (unstable supersaturation). Hyperoxalemia above this level is often seen in patients with primary hyperoxaluria. When bone histology was studied along with serum oxalate-related substances before and after parathyroidectomy, the serum oxalate level was not correlated with any of the parameters assessed.
2.Alanine-glyoxylate aminotransferase (AGT) is one of glyoxylate detoxifying enzyme localized in the peroxisome of hepatocytes that handle glyoxylate converted from glycolate. Glyoxylate reductase is localized in hepatocytes and other tissues, and it minimizes oxalate production from glyoxylate. Deficiency of vitamin B6, a cofactor of AGT, causes oxalosis and hemodialysis patients tend to be deficient in water -soluble vitamins. Oxalate precursors (glyoxylate, glycolate, hydroxyproline, hydroxypyruvate, xylitol, etc.) augment oxalate production in vitamin B6-deficient rats. Dialysis patients should avoid a diet containing oxalate precursors and such dietary restriction appears to be useful in treating hyperoxalemia.
3.Capillary electrophoresis combined with mass spectrometry improves the sensitivity of measuring serum oxalate by several-fold, enabling the serum levels of oxalate and glycolate to be easily determined. Using this method, we can confirm peaks that were previously thought to be oxalate precursors. Repeated measurement of serum oxalate allows us to get some new ideas for a highly sensitive oxalate assay, which will eventually be developed. These are the fruits obtained by the financial support of the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
In conclusion, we acknowledge the financial support for our research on oxalate in dialysis patients and hope that the results obtained in our experiments may be beneficial for the management of dialysis patients in the near future. This is not the end of our research, but instead represents a stepping stone. We are very eager to continue the same research and we hope for continuing support. Less
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