Abstract: Objective  This study aimed to use a two-sample Mendelian randomization approach to investigate the causal relationship between smoking behavior and chronic renal failure, along with related renal disease markers.  Methods  Using R Studio and packages such as TwoSampleMR for analysis, data from relevant large-scale genome-wide association studies were downloaded from public databases. Single nucleotide polymorphism sitess serving as instrumental variables were extracted for analysis. The results were mainly analyzed by Inverse variance weighted method for significance analysis and heterogeneity test, and the results were analyzed for horizontal multiplicity of results using MR-Egger intercept and MR-PRESSO methods. In addition, funnel plots and the leave-one-out method were used to confirm the potential bias and the robustness of the results.  Results  The instrumental variables included in the study were chronic renal failure (n=22), estimated glomerular filtration rate (n=17), urinary albumin (n=21), urinary microalbumin (n=22), haematuria (n=18), and cystatin C (n=9). The results of the inverse variance weighted method showed that smoking behavior was associated with chronic renal failure (OR=1.216, 95% CI: 1.051～1.408, P=0.009); lower estimated glomerular filtration rate (OR=0.990，95% CI: 0.984～0.996, P＜0.001); higher albumin urine (OR=1.051, 95% CI: 1.027～1.076, P＜0.001); higher microalbumin urine (OR=1.065, 95% CI: 1.021～1.110, P=0.003); haematuria (OR=1.002. 95% CI: 1.001～1.003, P=0.005); and higher cystatin C (OR=1.050, 95% CI:1.001～1.101, P=0.046) were causally related.  Conclusion  Smoking behavior leads to an increased risk of chronic renal failure and worsening of key renal function indicators, suggesting that smoking is a risk factors for renal disease. Smoking cessation can help prevent the development of kidney disease in smokers.

Key words: Chronic renal failure, Chronic kidney disease, Smoking behavior, Mendelian randomization