Pioglitazone in diabetic kidney disease: forgotten but not gone

Abstract

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.

Pioglitazone - the forgotten drug with multidirectional action

“…Jego bezpośrednie działanie może polegać na poprawie hiperfiltracji, klirensu kreatyniny, hamowaniu przebudowy tętniczek przedkłębuszkowych oraz stymulacji endogennych komórek macierzystych nerek i zwiększaniu wychwytu albumin w kanalikach nerkowych. Możliwe mechanizmy ochrony przed cukrzycową chorobą nerek obejmują również działanie przeciwzwłóknieniowe, przeciwzapalne, hamujące proliferację komórek i apoptozę [31].…”

GLP-1 receptor agonists, SGLT-2 inhibitors, and obstructive sleep apnoea: can new allies face an old enemy?

“…The upregulation (activity and number) of SGLT2 in patients with T2D contributes to approximately 20% to 30% higher tubular maximum renal glucose reabsorptive capacity (T m G) and enhanced renal threshold for glucose excretion (RT G ). This in turn creates a vicious cycle and contributes to the pathogenesis and maintenance of high glucose levels [78][79][80][81].…”