The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study

Area of Science:

• Nephrology
• Immunology
• Genetics

Background:

• Kidney diseases are often linked to inflammatory responses and leukocyte counts.
• Previous observational studies suggest a correlation but cannot establish causality.
• Mendelian randomization (MR) can explore causal relationships between leukocyte counts and kidney diseases.

Purpose of the Study:

• To investigate the causal relationship between four leukocyte counts (neutrophils, eosinophils, basophils, lymphocytes) and various kidney diseases using MR.
• To differentiate causal links from mere associations in kidney disease pathogenesis.

Main Methods:

• Utilized large-scale genome-wide association study databases for leukocyte traits (exposure) and renal diseases (outcome).
• Employed Mendelian randomization with inverse variance weighted (IVW), weighted median, and MR-Egger regression methods.
• Performed sensitivity analyses and multivariable MR to adjust for covariates.

Main Results:

• Increased neutrophil count is a risk factor for chronic renal failure (CRF).
• Increased basophil count is a risk factor for CRF and renal tubular dysfunction but a protective factor for hypertensive heart/renal disease.
• Increased lymphocyte count is a risk factor for hypertensive renal disease; increased eosinophil count is a risk factor for renal complications in type 1 diabetes.

Conclusions:

• Specific leukocyte counts have distinct causal effects on different kidney diseases.
• Neutrophils and basophils are implicated as risk factors for chronic renal failure.
• Basophils show a complex role, acting as both risk and protective factors depending on the specific renal condition.