BACKGROUND: It is well known that the anemia of chronic renal failure is associated with a blunted erythropoietin response. However, it is not clear why this response is blunted. Oxygen tension is an important regulator of erythropoietin production and release, but the effect of reduced renal mass on renal tissue oxygen tensions is currently unknown. METHODS: A computer-based simulation was used to determine how alterations in filtration fraction might impact on renal tissue oxygen tensions. In addition, direct measurements of oxygen tension with needle electrodes were employed, as well as conventional physiological measurements and ELISA measurements of plasma and tissue erythropoietin concentrations in rats subjected to 5/6th nephrectomy. RESULTS: Remnant kidney rats had 39% and 52% decreases in tissue and plasma erythropoietin concentrations, respectively, that correlated with 73% increased oxygen tensions in both cortex and outer medulla in the remnant kidney (all P < 0.01). Estimations of filtration fraction were decreased by approximately 36% in the rats bearing remnant kidneys. CONCLUSIONS: Higher oxygen tensions were observed in the remnant kidneys. We suggest that higher oxygen tensions are caused by a decrease in filtration fraction, and that these higher tissue oxygen tensions result in decreased renal erythropoietin production and anemia.
BACKGROUND: It is well known that the anemia of chronic renal failure is associated with a blunted erythropoietin response. However, it is not clear why this response is blunted. Oxygen tension is an important regulator of erythropoietin production and release, but the effect of reduced renal mass on renal tissue oxygen tensions is currently unknown. METHODS: A computer-based simulation was used to determine how alterations in filtration fraction might impact on renal tissue oxygen tensions. In addition, direct measurements of oxygen tension with needle electrodes were employed, as well as conventional physiological measurements and ELISA measurements of plasma and tissue erythropoietin concentrations in rats subjected to 5/6th nephrectomy. RESULTS: Remnant kidney rats had 39% and 52% decreases in tissue and plasma erythropoietin concentrations, respectively, that correlated with 73% increased oxygen tensions in both cortex and outer medulla in the remnant kidney (all P < 0.01). Estimations of filtration fraction were decreased by approximately 36% in the rats bearing remnant kidneys. CONCLUSIONS: Higher oxygen tensions were observed in the remnant kidneys. We suggest that higher oxygen tensions are caused by a decrease in filtration fraction, and that these higher tissue oxygen tensions result in decreased renal erythropoietin production and anemia.
Authors: Asada Leelahavanichkul; Qin Yan; Xuzhen Hu; Christoph Eisner; Yuning Huang; Richard Chen; Diane Mizel; Hua Zhou; Elizabeth C Wright; Jeffrey B Kopp; Jürgen Schnermann; Peter S T Yuen; Robert A Star Journal: Kidney Int Date: 2010-08-25 Impact factor: 10.612
Authors: Wanja M Bernhardt; Michael S Wiesener; Paul Scigalla; James Chou; Roland E Schmieder; Volkmar Günzler; Kai-Uwe Eckardt Journal: J Am Soc Nephrol Date: 2010-11-29 Impact factor: 10.121
Authors: Sandra Villanueva; Cristian Suazo; Daniela Santapau; Francisco Pérez; Mariana Quiroz; Juan E Carreño; Sebastián Illanes; Sergio Lavandero; Luis Michea; Carlos E Irarrazabal Journal: PLoS One Date: 2012-07-02 Impact factor: 3.240