Preexisting Hyperuricemia Before High-Altitude Ascent is Associated with a Slower Recovery of Estimated Glomerular Filtration Rate Following Descent.

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.

Mibefradil Alleviates High-Glucose-induced Cardiac Hypertrophy by Inhibiting PI3K/Akt/mTOR-mediated Autophagy.

Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in a high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated through immunofluorescence, and mRNA expression of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain) was assessed by using quantitative real-time polymerase chain reaction. Changes in the expression of p-PI3K, p-Akt, and p-mTOR were evaluated using Western blotting, and autophagosome formation was detected using transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil on high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study shows that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with diabetes mellitus.