The rats subjected to a longer period of hyperglycemia (12 weeks) experienced further kidney metabolic alterations that were not reversed in the subsequent 12 weeks of glycemic control, such as fumarate accumulation, increased TGF-β protein expression, decreased PGC-1α expression, and downregulation of mtDNA methylation and hydroxymethylation, and these effects were concomitant with sustained decreases in uric acid clearance and pAMPK levels. The gene discussed is TGFB1; the disease is Hyperglycemia.