Causal relationship between circulating immune cells and diabetic nephropathy: A Mendelian randomization study

Area of Science:

• Immunology
• Genetics
• Nephrology

Background:

• Diabetic nephropathy (DN) is a major complication of diabetes, leading to end-stage renal disease.
• The causal factors linking circulating immune cells to DN progression remain incompletely understood.

Purpose of the Study:

• To investigate the causal relationship between circulating immune cells and diabetic nephropathy (DN) using Mendelian randomization.
• To identify potential immune cell biomarkers for DN risk and progression.

Main Methods:

• Mendelian randomization analysis utilizing genome-wide association study summary statistics for circulating leukocytes, lymphocyte subgroups, and DN.
• Sensitivity analyses and horizontal pleiotropy examination to ensure the robustness of findings.

Main Results:

• A significant causal association was found between increased eosinophil counts and a higher risk of DN (OR: 1.21, 95% CI: 1.07-1.37, P = .00027).
• This association remained robust after sensitivity analyses.
• No causal link was observed between lymphocyte flow cytometric subgroups and DN.

Conclusions:

• Elevated eosinophil counts may be a causal factor in DN progression, potentially contributing to end-stage renal disease.
• Eosinophil counts could serve as a potential biomarker for DN diagnosis and management.
• Larger genome-wide association study data are required to validate the lack of a causal relationship between lymphocyte subtypes and DN.