Pioglitazone in diabetic kidney disease: forgotten but not gone

Diabetic kidney disease (DKD) is described in approximately 20–40% of all diabetic patients and is associated with significant cardiovascular and all-cause mortality. The involvement of multiple metabolic, haemodynamic, inflammatory, and tubular pathways in the pathophysiology of DKD generates the need for multitargeted treatment approaches to improve its development at all levels and delay or even reverse its progression. Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin on its cellular targets, mainly at the level of adipose tissue. Pioglitazone, currently the main thiazolidinedione in clinical practice, has achieved significant improvements of albuminuria in patients with type 2 diabetes. It can also interfere with most cellular pathways involved in the development and evolution of DKD. This paper explores the pathophysiological mechanisms governing its possible nephroprotective activity during a diabetic state. It also discusses its future role to ameliorate the global burden of DKD.