Association of Smoking, Smoking Cessation, and Genetic Susceptibility With Chronic Kidney Disease Risk

Rationale & Objectives: Chronic kidney disease (CKD) is a major public health issue, and smoking is a key modifiable risk factor.This study aimed to assess the associations of smoking and smoking cessation with incident CKD in later life, as well as the joint effects and interactions with genetic susceptibility.Study Design: Prospective cohort study.Setting & Participants: A total of 427,396 UK Biobank participants with available smoking and kidney function data, free of CKD at baseline (eGFR 60 mL/min/1.73 and UACR 30 mg/g), were included in this study.Exposure(s): Smoking status, including current smoking, former smoking, and smoking cessation during follow-up, was assessed using repeated touchscreen questionnaires.Outcomes: Incident chronic kidney disease (CKD) identified using ICD-10 and OPCS-4 codes from primary care, hospital inpatient, and death registry records, with baseline CKD defined as eGFR <60 mL/min/1.73m or albuminuria >30 mg/L.Analytical Approach: Cox proportional hazards regression models were used to estimate the association between smoking status and incident CKD, with secondary and sensitivity analyses performed to confirm the robustness of the findings.Results: Among 191,774 smokers included in the primary analysis, 13,726 incident cases of chronic kidney disease were documented over a median follow-up of 13.5 years.Compared with current smokers, quitters had the lowest risk of CKD (HR: 0.69, 95% CI: 0.57 -0.84), and former smokers also showed a significantly reduced risk (HR: 0.80, 95%J o u r n a l P r e -p r o o f CI: 0.76 -0.83) after full adjustment.Limitations: Potential misclassification of smoking and cessation status, possible under-ascertainment of CKD, residual confounding, and limited generalizability.Conclusion: Smoking cessation was associated with a reduced risk of chronic kidney disease compared to continued smoking.