Multifactorial factors include reducing the content of DDAH in the kidneys, reducing ADMA excretion in the urine, and reducing DDAH activity in diabetes mellitus, which may lead to increased plasma ADMA concentrations in patients with advanced DKD and impaired endothelial nitric oxide synthase function, thereby making AVF more prone to poor maturation and dysfunction. The gene discussed is NOS3; the disease is diabetic kidney disease.