Zhao, Linggong, Yujie Huang, and Xiaoling Tan. Preexisting hyperuricemia before high-altitude ascent is associated with a slower recovery of estimated glomerular filtration rate following descent. High Alt Med Biol. 00:00-00, 2024. Objectives: Hypoxia at high altitudes results in elevated uric acid (UA) and reduced estimated glomerular filtration rate (eGFR). However, the impact of a prolonged high-altitude sojourn on UA levels and renal function in patients with preexisting hyperuricemia warrants further exploration. The study was to investigate the eGFR and related factors in patients with preexisting hyperuricemia following exposure to high altitude. Methods: The study included 345 participants, who worked at a high altitude for 1 year. Anthropometric and laboratory indices were collected before ascent (i.e., baseline), as well as 20 and 80 days after descent. The participants were categorized into individuals with hyperuricemia (HUA) or normal uric acid (NUA) group based on the presence or absence of hyperuricemia at baseline. Results: No difference in baseline eGFR was observed between the two groups before ascend or on day 20 after descent (p > 0.05). However, on day 80, eGFR of the HUA group was lower compared with the NUA group (p < 0.05). Correlations existed between post-descent eGFR levels and variables, including sampling time, UA levels, total and direct bilirubin, and baseline grouping. Conclusions: After high-altitude exposure, the recovery of eGFR was delayed in participants with preexisting hyperuricemia. Preexisting hyperuricemia and high-altitude hypoxia jointly contribute to renal impairment.

Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).
Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of 13 C2- and 15 N-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.
Tot-Hb increased by 4.7% ± 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of 13 C- (normoxia) and 15 N- (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis.
We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.