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Programmed cell death 1 pathway and cognitive function in patients undergoing hemodialysis.
Kazuhiko Kato1,2, Akio Nakashima1, Chiharu Aizawa1,2
1Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Journal of Nephrology
|May 19, 2026
Summary
Cognitive impairment in hemodialysis patients is linked to the PD-1 pathway. Higher levels of soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) indicate increased risk, suggesting potential therapeutic targets.
Area of Science:
- Nephrology
- Immunology
- Neuroscience
Background:
- Cognitive impairment is prevalent in hemodialysis patients, impacting quality of life and survival.
- The programmed cell death 1 (PD-1) pathway is implicated in immune evasion, chronic inflammation, and aging.
- The role of the PD-1 pathway in hemodialysis-associated cognitive impairment is not well understood.
Purpose of the Study:
- To investigate the association between the PD-1 pathway and cognitive impairment in elderly hemodialysis patients.
- To explore the relationship between serum soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) levels and cognitive function.
Main Methods:
- Cross-sectional study of 384 hemodialysis patients aged ≥65 years across 7 centers.
- Cognitive function assessed using Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE).
- Serum sPD-1 and sPD-L1 levels measured via ELISA; multivariable logistic regression used for analysis.
Main Results:
- 61.2% of patients had MoCA scores below the impairment cutoff; 10.2% had MMSE scores below the cutoff.
- Elevated sPD-1 levels correlated with cognitive impairment by both MoCA and MMSE.
- Higher sPD-L1 levels were associated with MoCA-defined cognitive impairment (OR, 2.53; P = .009).
Conclusions:
- The PD-1 pathway may play a significant role in cognitive impairment among hemodialysis patients.
- sPD-1 and sPD-L1 levels could serve as biomarkers for risk stratification.
- Findings suggest potential for PD-1 pathway-targeted interventions to address cognitive decline in this population.
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