Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients

Sarcopenia, abbreviated as muscle loss, is a prevalent complication among patients with chronic kidney disease (CKD), particularly those with end - stage renal disease (ESRD). It significantly impacts patients' quality of life. The prevalence of sarcopenia in patients receiving maintenance hemodialysis (MHD) ranges from 32.7% to 73.5%, which is substantially higher than that in the general population (5% - 13%). Sarcopenia significantly elevates the mortality risk in MHD patients. Specifically, sarcopenia patients experience an increased all - cause mortality rate, a heightened risk of cardiovascular events, a decline in quality of life, and an augmented risk of falls and fractures. A close pathophysiological relationship exists between the hypoxia - inducible factor - 1 (HIF - 1) pathway and sarcopenia. HIF - 1α serves as a key transcription factor for cells to respond to hypoxic conditions. Under normoxic conditions, HIF - 1α is hydroxylated by prolyl hydroxylase (PHD) and subsequently undergoes ubiquitination - mediated degradation. Conversely, under hypoxic circumstances, HIF - 1α is stably expressed, translocates into the nucleus, and activates downstream target genes. HIF - 1α promotes the expression of genes associated with glycolysis, such as GLUT1 and LDHA, while inhibiting mitochondrial oxidative phosphorylation. This results in a shift of skeletal muscle energy metabolism from aerobic to anaerobic pathways. Research has revealed that the protein level of HIF - 1α is significantly decreased in sarcopenia patients. Roxadustat capsules, an oral medication, represent the world's first small - molecule hypoxia - inducible factor prolyl hydroxylase inhibitor (HIF - PHI) developed for the treatment of renal anemia. The physiological function of HIF - 1α not only enhances the expression of erythropoietin but also upregulates the expression of erythropoietin receptors and proteins involved in promoting iron absorption and circulation. Theoretically, roxadustat has the potential to improve sarcopenia. However, due to its prominent effect on anemia correction, it is currently only clinically applicable to anemic patients. This study aims to use ESA as a control to investigate the effect of roxadustat on sarcopenia in hemodialysis patients during the treatment of renal anemia.