2007 Fiscal Year Final Research Report Summary
Intra and extra renal erythropoietin production in chronic renal failure and possibility of erythropoietin gene therapy
| Project/Area Number |
17590815
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
MATSUBARA Mitsunobu Tohoku University, Graduate School of Medicine, Associate professor (30282073)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Keywords | kideny / anemia / renal physiology / renal failure / erythropoietin / renal tubule / liver / gene |
|---|
| Research Abstract |
Anemia occurs as one of severe complications of chronic renal failure (CRF). Insufficient erythropoiesis is one on the main reasons for renal anemia, thus, we closely examined the erythropoietin (EPO) production in both kidney and liver of a rat model for CRF and assessed the possibility of gene therapy. To this end, we prepared rats underwent 5/6 nephrectomy or sham-operation. After examining basal ability of erythropoiesis by measuring plasma EPO concentration and EPO mRNA in kidney and liver, we investigated the alteration of erythropoiesis in response to both hemo-concentration and hemo-dilusion. The results are as follows: 1. Basal EPO production of the kidney is conserved in rats with mild to moderate renal failure, and it is impaired in rats with advanced renal failure. 2. Compensatory EPO production occurs from the early stage of renal failure. 3. Responsive EPO production to both hemoconcentration and homodilusion is well conserved in rats with mild to moderate renal failure, and only rats with advanced renal failure do not adequately increase EPO production to hemodilusion. 4. Rats with advanced renal failure do not tolerate hemoconcentration. These results indicate the administration of EPO is required only to advanced CRF, but excess erythropoiesis might have adverse effects. Therefore, EPO gene therapy, which would not control erythropoiesis within small range, could not be applied to the anemia treatment in CRF.
|
