| Project/Area Number |
16590803
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
KIMURA Kenjiro St.Marianna University School of Medicine, medical department, Professor, 医学部, 教授 (00161555)
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| Co-Investigator(Kenkyū-buntansha) |
菅谷 健 シミック株式会社, 経営企画部, FABPプロジェクトリーダー (40381561)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | diabetic nephropathy / liver-type fatty acid binding protein / tubulointerstitial damage / biomarker / transgenic animals / urinary fatty acid / urinary albumin / early diagnosis / ネフローゼ症候群 / 尿蛋白 |
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| Research Abstract |
The number of patients with Diabetic nephropathy (DN) is increasing worldwide. DN is a principal cause of kidney disease that ultimately progress to end-stage renal failure. Liver-type FABP (L-FABP) of 14.4kDa is expressed in the proximal tubule. We established a two step sandwich enzyme linked immunosorbent assay (ELISA) method for determining human L-FABP in urine. In this study, we examined the dynamics of renal L-FABP and clinical significance of urinary renal L-FABP in DN.
1)Experimental study
Because L-FABP is not expressed in murine kidneys, we established transgenic (Tg) mice with the human L-FABP gene. In streptozotocin (STZ)-induced DN model with these Tg mice, we found that the expression of L-FABP in the proximal tubules was up-regulated and urinary excretion of renal L-FABP was accelerated.
2)Clinical study
・Urinary L-FABP was measured in patients with non-insulin dependent diabetes mellitus (n=147) by ELISA using specific monoclonal antibodies. The level of urinary L-FABP was significantly increased according to the severity of DN. Furthermore, urinary L-FABP in the patients with normoalbuminuria was significantly higher than that in the normal controls (p=0.0000). Urinary L-FABP may be a useful diagnostic risk marker for progression of diabetic nephropathy.
・Urinary L-FABP was measured in patients with nephrotic syndrome due to DN (n=8) and those with minimal change nephrotic syndrome (MCNS, n=12). Urinary fatty acid (FA) and urinary L-FABP were significantly elevated in DN than compared to MCNS. The degree of tubulointerstitial damage was significantly more severe in patients with DN compared to those with MCNS. Elevated urinary excretion of FA is a reflection of FA overload in the proximal tubules and FA may be an important promoter of tubulointerstitial damage in DN patients. Urinary L-FABP reflects the FA stress to the proximal tubules, which cause severe tubulointerstitial damage.
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