Smoking as a causative factor in chronic kidney disease: a two-sample Mendelian randomization study.

Area of Science:

• Genetics and Epidemiology
• Public Health
• Nephrology

Background:

• Smoking is a known health risk, but its direct causal link to chronic kidney disease (CKD) requires further investigation.
• Understanding the specific smoking behaviors associated with CKD is crucial for public health interventions.

Purpose of the Study:

• To investigate the causal relationship between various smoking behaviors and the risk of developing CKD.
• To determine the impact of smoking initiation, cessation, intensity, and duration on CKD incidence.

Main Methods:

• Utilized bivariate causal analysis and two-sample Mendelian randomization (MR) with genome-wide data.
• Employed inverse variance weighted (IVW) method, sensitivity analyses, pleiotropy assessments, and mediation analyses.
• Validated findings using independent external datasets.

Main Results:

• Confirmed positive associations between CKD and smoking initiation, earlier age of initiation, higher daily cigarette consumption, and lifetime smoking.
• Demonstrated a significant protective effect of smoking cessation against CKD.
• Identified body mass index, cardiovascular disease, hypertension, and type 2 diabetes as mediators of smoking's effect on CKD.

Conclusions:

• Establishes smoking as a significant contributing factor to the development of CKD.
• Supports public health strategies focused on smoking reduction and cessation to decrease CKD prevalence.