RAGE activation in macrophages and development of experimental diabetic polyneuropathy.

Type 1 diabetes is associated with a progressive decline in kidney function. With improved survival, more individuals with type 1 diabetes are reaching an age where irreversible loss of kidney function can impact health and clinical outcomes. Although current standard of care has markedly reduced the incidence of fast-progressing kidney disease characterized by heavy albuminuria, and improved patient survival, these same interventions have not slowed kidney decline in most patients. An urgent need remains to develop a different foundational approach to type 1 diabetes with early kidney protection considered as important as glucose control. Toward this goal, a number of new renoprotective strategies have emerged over the last decade, including glucagon-like peptide 1 receptor agonists, aldosterone antagonists, and sodium-glucose cotransporter 2 inhibitors. For each therapy unequivocal activity has been demonstrated in patients with type 2 diabetes and kidney disease, which has prompted some clinicians to use agents off-label in patients with type 1 diabetes, so pressing is their need. However, before such important benefits can be translated to patients with type 1 diabetes, the risk of serious adverse effects must be carefully considered and the balance of efficacy and safety verified in clinical trials. In this review we consider the potential role of adjunctive therapy in type 1 diabetes in improving kidney outcomes.