Abstract: SA-PO219
Anemia Disrupts Renal Compensatory Responses After Uninephrectomy in Mice
Session Information
- Anemia and Iron Metabolism: Basic
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 201 Anemia and Iron Metabolism: Basic
Authors
- Nakano, Daisuke, Kagawa University, Kagawa, Japan
- Nishiyama, Akira, Kagawa University Medical School, Kita-Gun, Japan
Background
Kidneys with functional nephrons are essential for our life, but the numerous factors could reduce the numbers of nephron day by day. Kidney has ability to adapt its size and function against the nephron loss to maintain total renal function, for example, in both donor and recipient in renal transplantation. However, the factors that regulate this compensation have not been fully clarified yet. Hereby we examined the effects of erythropoietin (EPO)/anemia on the compensatory renal hypertrophy in mice model of renal anemia.
Methods
The mice lacking renal EPO production were used.
Results
The anemic mice showed renal compensatory responses, such as GFR more than half and cell hypertrophy, similar to normoxemic mice at week 1 after unilateral nephrectomy (UNX). However, the compensation was disrupted only in anemic mice at week 4 after UNX; the mice lacking EPO receptor in the kidney showed successful compensation. The disruption was accompanied by the increased oxidized glutathione and sustainable phosphorylation of ribosomal protein S6, a marker of mTOR activation, which had been decreased after successful compensation in the normal mice. In the renal interstitium of anemic mice at week 4 of UNX, the number of cells promoting epo gene transcription (but disable to produce EPO protein in the mice) was reduced even under the anemia, and the number of α-smooth muscle actin-positive cells was increased, suggesting the transdifferentiation of EPO-producing cells. These changes were restored by the supplementation of rEPO.
Conclusion
Anemia does not affect the onset of compensatory renal hypertrophy after UNX, but disrupts the persistent compensation process.
Funding
- Government Support - Non-U.S.