Metabolic memory in diabetic kidney disease

Metabolic memory refers to the long-lasting negative impact of poor blood glucose control on diabetic micro- and macrovascular complications, which persists even after subsequent improved glycemic control. Underlying mechanisms of the metabolic memory include reactive oxygen species (ROS), advanced glycation endproducts (AGEs), and epigenetic modifications. Furthermore, hyperglycemia-associated ROS, AGEs, and epigenetic changes impair repair capacity, which promote cellular senescence. Because epigenetic changes and senescence are in principle reversible, a better understanding of the processes underlying metabolic memory may enable new therapeutic approaches. For example, the cell-protective coagulation protease activated protein C (aPC) can reverse glucose-dependent and p21-induced senescence, or sirtuins may remove glucose-induced epigenetic acetylation marks. In addition, biomarkers of epigenetic changes or senescence may support innovative precision medicine.