Abstract: Objective: To investigate the association between plasma glial cell line-derived neurotrophic factor (GDNF) levels and insomnia in patients undergoing maintenance hemodialysis (HD). Methods: This single-center cross-sectional study enrolled 29 stage 1-3 chronic kidney disease (CKD) patients without insomnia (mean age: 59.93?±?15.03 years) and 103 HD patients (mean age: 59.89?±?11.64 years). Based on Pittsburgh Sleep Quality Index (PSQI) scores, HD patients were categorized into three groups: HD without insomnia (PSQI ≤ 5, n=41), mild insomnia (6 ≤ PSQI ≤ 10, n=37), and moderate to severe insomnia (PSQI ≥ 11, n=25). Plasma GDNF concentrations were measured and sleep quality was assessed using the PSQI. Results: The median GDNF level differed significantly between the non-insomnia CKD group and the non-insomnia HD group (Z=2.754, P=0.006). Among HD patients, age (F=8.238, P=<0.001), dialysis duration (X2=6.094, P=0.047), and GDNF levels (X2 =8.370, P=0.015) showed significant differences across insomnia groups. Pairwise comparisons revealed that both age and GDNF levels were significantly different between the non-insomnia and mild insomnia groups (t=2.263，P=0.026；Z =2.517，P=0.012), as well as between the non-insomnia and moderate-to-severe insomnia groups (t=4.011，P<0.001；Z =2.360，P=0.018). Spearman correlation analysis indicated that plasma GDNF levels were positively correlated with PSQI total score (ρ = 0.290, t=3.045，P=0.003), as well as with components including subjective sleep quality (ρ= 0.334，t=3.561，P<0.001), sleep latency(ρ= 0.311，t=3.289，P=0.001), sleep duration(ρ= 0.217，t=2.234，P=0.027), sleep efficiency(ρ= 0.241，t=2.496，P=0.014), and sleep disturbances (ρ= 0.227，t=2.342，P=0.021). Conclusion: GDNF level was associated with insomnia in HD patients. GDNF may serve as a novel biomarker for insomnia in HD patients.

Key words: Glial cell line-derived neurotrophic factor, Sleep disturbance, Hemodialysis；Pittsburgh sleep quality index