| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Kazuhiro Aichigakuin University, Dental School, Assis.Professor, 歯学部, 講師 (30301625)
YUZAWA Yukio School of Medicine, Research Assoc., 医学部, 助手 (00191479)
HASEGAWA Takaaki School of Medicine, Professor, 医学部, 教授 (80198720)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
The aim of this project was to investigate the mechanisms of tubulointerstitial injury associated with proteinuria, since tubulointerstitial injury and proteinuria are closely related with each other and both of them are the better predictors for prognosis of renal injury. In the present study, the role of complement present in the tubular fluid of nephrotic subjects was investigated. In the first part of experiment using rats made nephrotic by aminonucleoside in which significant tubulointerstitial injury and tubular deposition of complement were observed at 7 days, the following results were obtained. (1) Depletion of serum complement by cobra venom factor (CVF) did not affect proteinuria, but significantly reduced deposition of complement in the tubules and tubulointerstitial injury, (2) soluble CR1, an inhibitor of complement activation at C3 level, had the same effects as CVF.In the second part, complement activation products (CAP, i.e., iC3b and Bb at C3 level, and MAC at C9 level) were measured in the patients with various glomerular diseases. The results *otained were as follow ; (1) Urinary excretion of CAP was positively correlated with the amount of proteinuria, (2) among proteinuric patients, those with focal glomerular sclerosis and diabetic nephropathy showed significantly elevated amount of CAP in the urine, (3) in case of membranous nephropathy, urinary excretion of MAC was increased, whereas iC3b and Bb were not increased, (4) in the patients with renal insufficiency, correction of acidosis by sodium bicarbonate significantly reduced urinary excretion of CAP without affecting the serum level of CAP and urinary protein excretion. These results indicate that, in the proteinuric condition, complement components present in the urine are activated in the tubular lumen and injure the tubular cells resulting in the promotion of tubulointerstitial injury.
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