Objectives: Chronic kidney disease (CKD) is associated with various modifiable risk factors, including metabolic factors and genetic predispositions. We aimed to investigate the individual and combined contribution of acquired metabolic risk factors and genetic risk with incident CKD. Methods: Using UK Biobank study, we selected four acquired metabolic risk factors including hypertension, diabetes obesity, and hyperlipidemia (high low-density lipoprotein cholesterol [LDL-C] level). Polygenic risk scores (PRS) for these factors were also derived from PRS data by Genomics PLC as part of UK Biobank project. The primary outcome was incident CKD. The risk of CKD was determined using Cox proportional hazards model. The population attribution fraction (PAF) of metabolic factors and PRSs were calculated to estimate the relative contribution of each factor to CKD. Results: This study included 171,955 participants, with a mean age 55.7 years and 86,153 (50.1%) being men. During the 12.8-year follow-up period, 8,641 events of CKD occurred. Hypertension exhibited the highest PAF for CKD at 17.4% (95% CI, 16.1-18.7), followed by diabetes (5.4 [5.0-6.0]) and obesity (9.6% [8.7-10.7]), respectively. However, high LDL-C (>100mg/dL) did not show a significant attribution to CKD risk. Similar to metabolic factors, PRSs for hypertension, diabetes, and BMI, but not LDL-C, significantly contributed to CKD risk, with the corresponding PAFs (95% CIs) of 14.7 (12.7-16.6), 5.5 (3.3-7.6), and 5.4 (3.4-7.4), respectively. The attribution of hypertension to CKD risk was more pronounced in high genetic risk groups of hypertension and diabetes, whereas hypertension did not contribute to CKD risk in high genetic risk groups of obesity and LDL-C. Conclusions: In this prospective cohort study, there was a complex interplay between acquired metabolic risk factors and genetic predisposition in the development of CKD. This finding may provide an informative insight to the management of modifiable risk factors of CKD, considering their dynamic relationship with genetic risk factors.