α-Klotho, hypoxia-inducible factor-2α, and oxidative stress in hemodialysis ‒ interactions with anemia, secondary hyperparathyroidism, and intradialytic hypotension

Introduction and aim. End-stage renal disease (ESRD) is associated with oxidative stress (OS) and hormonal disturbances linked to anemia, secondary hyperparathyroidism (SHPT), and intradialytic hypotension (IDH). This study evaluated the expression of α-Klotho (α-KL) and hypoxia-inducible factor-2α (HIF-2α) together with OS markers in hemodialysis (HD) patients and explored their interrelationships and associations with anemia, SHPT, and IDH. Material and methods. Fifty HD patients and 50 healthy controls were evaluated for clinical and biochemical parameters, malondialdehyde (MDA), catalase (CAT) activity, and α-KL and HIF-2α expression. Correlation and network analyses were used to evaluate molecular interactions. Results. Anemia, SHPT, and IDH were identified in 72%, 44%, and 18% of HD patients, respectively. Compared with controls, HD patients demonstrated significantly higher MDA levels and lower α-KL and HIF-2α expression, and CAT activity (all p<0.001). MDA positively correlated with parathyroid hormone (PTH) (r=0.26, p<0.01) and IDH (r=0.37, p<0.001), but inversely with hemoglobin (Hb) (r=−0.24, p<0.02) and CAT activity (r=−0.36, p<0.001). Lower α-KL and HIF-2α expression levels, together with reduced CAT activity, correlated positively with Hb (r=0.27–0.71) and inversely with PTH (r=−0.27 to−0.62) and IDH (r=−0.40 to−0.92) (all p<0.01). Positive intercorrelations were additionally found among α-KL, HIF-2α, and CAT (r=0.21–0.38, all p<0.05). Conclusion. Reduced α-KL and HIF-2α expression together with altered OS markers were associated with anemia, SHPT, and IDH in HD patients. The close interrelationships observed among α-KL, HIF-2α, and OS markers may reflect an integrated molecular pattern linked to dialysis-related complications. Additional prospective studies are warranted to further elucidate these relationships.