Abstract: The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and methods are useful for treatment or prevention of kidney failure, treatment of anemia, and other conditions commonly associated with kidney failure in order to increase survival and improve welfare in subjects with chronic renal failure. Overall, the embodiments of the invention can be accomplished by delivering an isolated nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of a subject and allowing expression of the encoded gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the subject, tissue specific constitutive expression is achieved. The embodiments of the invention also encompass delivery of a recombinant GHRH polypeptide or functional biological equivalent thereof.