Renal function and neurodegenerative diseases : a two-sample Mendelian randomization study.

Area of Science:

• Neuroscience
• Nephrology
• Genetics

Background:

• Observational studies suggest links between renal function and neurodegenerative diseases like Alzheimer's, Parkinson's, Lewy body dementia, and multiple sclerosis.
• The causal nature of these associations remains unclear.

Purpose of the Study:

• To investigate the potential causal relationships between key indicators of renal function and six major neurodegenerative diseases (NDDs).
• Utilizing Mendelian randomization to assess causality between blood urea nitrogen (BUN), chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

Main Methods:

• Employed a two-sample Mendelian randomization (MR) analysis.
• Used inverse-variance weighted (IVW) as the primary method for estimating causal effects.
• Performed sensitivity analyses including MR Egger regression, Cochran Q statistic, and leave-one-out methods to validate findings.

Main Results:

• No causal relationships were found between BUN, CKD, or eGFR and AD, familial AD, PD, LBD, FTD, or ALS.
• A potential causal relationship was identified between reduced eGFR and MS (OR, 4.89; P=0.01) via IVW analysis, but this was not consistently supported by sensitivity analyses.
• No causal association was observed between MS and BUN or CKD.

Conclusions:

• The study suggests a potential link between reduced eGFR and multiple sclerosis.
• Findings provide a basis for future research into the specific mechanisms connecting decreased kidney function and MS.