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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.
Background:
Cognitive impairment is common among patients undergoing hemodialysis and worsens their quality of life and survival. The programmed cell death 1 (PD-1) pathway-comprising the receptor PD-1 and its ligand programmed cell death ligand 1 (PD-L1)-was initially recognized as a mechanism of tumor immune evasion that was also involved in chronic inflammation and immune aging. However, its role in cognitive impairment remains poorly understood.
Methods:
In this cross-sectional study, patients aged ≥65 years undergoing hemodialysis were recruited from 7 centers. Global cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Serum soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) were measured by enzyme-linked immunosorbent assay. Multivariable logistic regression was used to adjust for age, sex, dialysis vintage, C-reactive protein, and other confounders.
Results:
Median age of the 384 patients was 74 years (interquartile range, 70-80), 67.5% were male, 61.2% scored below the MoCA score cutoff of 26, and 10.2% scored below the MMSE score cutoff of 24. Higher sPD-1 levels were associated with cognitive impairment as defined by both assessment tools; moreover, higher sPD-L1 levels were associated with MoCA-defined impairment (odds ratio, 2.53; 95% confidence interval, 1.26-5.06, P = .009). The association between sPD-1 and MMSE-defined impairment was stronger in patients without cancer history.
Conclusion:
These findings highlight the potential role of the PD-1 pathway in risk stratification and future interventions in cognitive impairment in patients undergoing hemodialysis.
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