Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

Area of Science:

• Nephrology
• Cardiology
• Genetics

Background:

• End-stage renal disease (ESRD) is a known risk factor for cardiovascular events.
• The causal relationship between mild-to-moderate kidney dysfunction and coronary heart disease (CHD) or stroke remains unclear.

Purpose of the Study:

• To investigate the causal link between estimated glomerular filtration rate (eGFR) and the risk of incident CHD and stroke.
• To determine if impaired kidney function, even in its early stages, contributes to cardiovascular disease development.

Main Methods:

• Utilized individual-level data from four large population studies (Emerging Risk Factors Collaboration, EPIC-CVD, Million Veteran Program, UK Biobank).
• Conducted Mendelian randomization analyses using a genetic risk score for eGFR in over 413,000 participants.
• Analyzed incident CHD and stroke events over 6.8 million person-years of follow-up.

Main Results:

• Observational analyses revealed U-shaped associations between eGFR and cardiovascular risk.
• Mendelian randomization showed a 14% increased CHD risk per 5 mL·min⁻¹·1.73 m⁻² lower genetically predicted eGFR in participants with eGFR <60 mL·min⁻¹·1.73 m⁻².
• No significant association was found for eGFR >105 mL·min⁻¹·1.73 m⁻²; stroke results were nonsignificant but consistent.

Conclusions:

• Mild-to-moderate kidney dysfunction is causally associated with an increased risk of CHD in individuals without pre-existing cardiovascular disease or diabetes.
• These findings underscore the significance of maintaining and managing kidney function as a preventive strategy for cardiovascular health.