Comparative response of EPO and soluble transferrin receptor at high altitude

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.

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).

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.

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.