AGING-ASSOCIATED IMMUNE SIGNATURE PREDICTS EARLY MORTALITY IN END-STAGE RENAL DISEASE: FINDINGS FROM THE iESRD STUDY

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AGING-ASSOCIATED IMMUNE SIGNATURE PREDICTS EARLY MORTALITY IN END-STAGE RENAL DISEASE: FINDINGS FROM THE iESRD STUDY

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Co-author 1

Kai-Hsiang Shu d04449012@ntu.edu.tw Far Eastern Memorial Hospital Division of Nephrology New Taipei City Taiwan *

Co-author 2

TienYu Owen Yang tienyu.owen.yang@gmail.com University of Oxford Nuffield Department of Population Health Oxford United Kingdom -

Co-author 3

Yen-Ling Chiu yenling.chiu@saturn.yzu.edu.tw Yuan Ze University Graduate Institute of Medicine Taoyuan Taiwan -

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Introduction

Immune cell subset distribution is altered in end-stage kidney disease, but it remains unknown if immune profiles predict patient survival outcomes in these patients. To investigate this, we conducted a prospective observational iESRD (Immunity in ESRD) study in adults receiving regular hemodialysis, excluding those with active infections or hospitalizations within the past three months.

Methods

Eleven immune cell subsets were analyzed by flow cytometry at baseline, including neutrophils, CD3-negative lymphocytes, four subsets of CD4 T lymphocytes, four subsets of CD8 T lymphocytes, and three subsets of monocytes. Immune cell distribution patterns were identified through data-driven principal component analysis (PCA).

Results

A total of 409 hemodialysis patients were recruited and followed for three years, during which 75 patients died. When cell subsets were analyzed separately, deceased patients had lower counts of CD4 naïve and CD8 naïve T cells but higher levels of CD4 effector memory and CD4 terminally differentiated T cells. PCA identified three major immune cell subset patterns—PC1, PC2, and PC3—accounting for 23%, 17%, and 14% of the variance, respectively. Notably, PC3 was associated with age. In multivariable-adjusted Cox regression analysis, PC3 independently predicted all-cause mortality (hazard ratio [HR] 1.31, P = 0.02) and cardiovascular death (HR 1.49, P = 0.04). Detailed analysis showed that PC3 was driven by the numbers of naïve CD8 T cells (27%) and non-classical monocytes (15%).

Conclusion

Our results indicate that data-driven immune cell subset patterns are independent predictors of all-cause and cardiovascular mortality in hemodialysis patients. The abstract was submitted for 2025 Annual Meeting of Taiwan Society of Nephrology.

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