Determinants of erythropoietin release in response to short-term hypobaric hypoxia

We measured blood erythropoietin (EPO) concentration, arterial O₂ saturation (Sa_O2), and urine P_O2 in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O₂ delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine P_O2 decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine P_O2 was closely related to EPO via a curvilinear relationship (r² = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa_O2 decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa_O2 (r = 0.41, P < 0.05) and no significant relationship with renal O₂ delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes ≥2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O₂ delivery to EPO-producing tissues.