Comparative response of EPO and soluble transferrin receptor at high altitude

PURPOSE: Soluble transferrin receptor (sTfR) classically raises with increased erythropoiesis, along with the rise in erythropoietin (EPO). However, the specific effect of altitude-induced erythropoiesis on sTfR remains poorly documented. This study investigated the response of sTfR during high-altitude exposure in human and verified that sTfR was related to EPO response in this case. METHODS: EPO, sTfR, red cell volume (RCV), ferritin, and iron intake were measured during: 1) experiment A (N = 8, 31 d at 5000-8848 m), at sea level (SL), and at the simulated altitude of 5000, 6000, 7000, and 8000 m; and 2) during experiment B (N = 10, 7 d at 4350 m), at SL, after 3, 5, and 7 d at 4350 m and 1-2 d after return to SL (RSL). RESULTS: In experiment A, progressive decompression from SL to 8000 m induced a large parallel rise in EPO (33.8-fold) and sTfR (5.9-fold), whereas ferritin was dramatically decreased and iron intake reduced. RCV was increased after 31 d of decompression. In experiment B, EPO peaked at day 3 at 4350 m, then declined later at altitude and returned to baseline values at RSL, whereas sTfR progressively rose at altitude (+86%) and remained elevated during RSL (+64%). Ferritin progressively declined at 4350 m, whereas iron intake was unchanged. RCV was not enhanced after exposure to 4350 m. CONCLUSION: In summary, sTfR mirrors EPO response for a given level of altitude hypoxia but differs from EPO response during transitory phases, such as early acclimatization or reoxygenation. Analysis of sTfR may therefore account for altitude-related erythropoiesis, at a time when EPO is blunted.