Peroxisome proliferator-activated receptor gamma agonists in renal disease

Abstract

Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARg) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARg receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARg agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARg agonists on renal function and revised the results of their utilisation in patients with different degrees of renal impairment, in dialysis patients, and in patients with diabetes mellitus after kidney transplantation. Finally, tolerability and safety profile of PPARg agonists in patients with reduced glomerular filtration rate are also analysed. European Journal of Endocrinology 154 613-621

PPAR-γ agonist rosiglitazone protects peritoneal membrane from dialysis fluid-induced damage

“…61 However, RSG may be considered as a safe drug for use in uremic status because it is metabolized in the liver and thus, the accumulation of the drug and the risk of severe and prolonged hypoglycemia are minimized. 62 We believe that our results provide evidence that inflammation can be considered as a potential therapeutic target to ameliorate PDrelated peritoneal membrane deterioration. Further studies of peritoneal inflammatory reaction will lead to the generation of more specific interventions with minimal side effects.…”

Mitochondrial Dysfunction Mediates Aldosterone-Induced Podocyte Damage

“…13 Among these, PPAR␥ is the target of thiazolidinediones, which are widely used as an insulin sensitizer in patients with type 2 diabetes. PPAR␥ agonists may have renoprotective effects in diabetic nephropathy, chronic renal insufficiency, and renal transplantation.…”

“…PPAR␥ agonists may have renoprotective effects in diabetic nephropathy, chronic renal insufficiency, and renal transplantation. 13 In particular, PPAR␥ agonist pioglitazone is protective in podocyte injuryassociated sclerosis, possibly by inhibiting podocyte apoptosis and macrophage infiltration, increasing VEGF expression and protecting against glomerular capillary loss. 14 However, little is known about the mechanism of action of PPAR␥ in podocytes.…”

Ibuprofen attenuates nephropathy in streptozotocin-induced diabetic rats

“…Furthermore, a previous study demonstrated that in Finnish adults with type 1 diabetes, the mortality associated with diabetes was almost entirely confined to those with chronic kidney diseases (13). Additionally, evidence indicates that PPARγ agonists alleviate certain symptoms in various types of renal disease (10,14,15). Together, these studies suggested PPARγ activation as an essential therapeutic strategy for kidney diseases caused by type 2 and 1 diabetes.…”