The reasons are multifactorial, including the age-related changes in the renal function (which favors sodium renal retention and loss of water), the presence of aged vessels, the higher probability for other comorbidities that worsen the renal function such as dehydration, CKD especially when treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), the advanced coronary artery disease, long-term HTN, and DM. The gene discussed is ACE; the disease is chronic kidney disease.