Thiazolidinediones and diabetic nephropathy: need for a closer examination?

Diabetic nephropathy is an important public health issue and a major challenge for modern nephrology, as it is the primary cause of end-stage renal disease. In addition to established risk factors for diabetic nephropathy progression (ie, hyperglycemia and hypertension), current knowledge suggests that other factors can be involved. Population studies show that insulin resistance and hyperinsulinemia are also associated with chronic kidney disease, and several background mechanisms could explain this relationship. The hypoglycemic class of thiazolidinediones that act through reduction of insulin resistance were found to protect against renal injury in diabetic animals and to reduce urinary albumin excretion in patients with type 2 diabetes and microalbuminuria. This renoprotective action is supported by relevant studies showing that thiazolidinediones act beneficially on most of the players involved in diabetic nephropathy progression. Recent studies have raised uncertainty about the cardiovascular safety of thiazolidinediones. After the latter issue is resolved, however, it would appear very interesting to conduct specific studies in patients with overt diabetic nephropathy to determine the effect of these agents on proteinuria and kidney disease progression.