Cigarette smoking promotes oxidative stress, endothelial dysfunction, and activation of the renin–angiotensin–aldosterone system; accelerates atherosclerosis; and contributes to glomerular injury and CKD progression. Smokeless tobacco products may also worsen CKM risk factors. High-risk alcohol use increases blood pressure, atrial fibrillation, cardiomyopathy, and overall cardiovascular mortality; relationships between low-to-moderate alcohol use and CKD/CVD risk are complex and may vary by CKM stage. The gene discussed is REN; the disease is endothelial dysfunction.