ABSTRACT
INTRODUCTION The most important cause of increased mortality and morbidity in diabetic patients is micro-and macrovascular complications. Diabetic microangiopathy consists of diabetic nephropathy, retinopathy, and possibly neuropathy.1 Diabetic kidney disease is associated with well-known morphological and functional renal alterations. The early stage is characterized by induction of growth factors and cytokines along with kidney growth, glomerular hyperfiltration and increased synthesis of extracellular matrix (ECM), leading to albuminuria and proteinuria in later diabetic nephropathy.2,3 The Diabetes Control and Complications Trial showed that hyperglycaemia is a major factor in the development of diabetic microvascular complications.1 Several bio-chemical pathways have been proposed to be involved, and to explain in part the adverse effects of hyperglycaemia. First, metabolic factors such as nonenzymatic glycation, polyol pathway activation, and diacylglycerol (DAG)-protein kinase C (PKC) activation will be discussed. Second, growth factors and cytokines, the most important being growth hormone (GH), insulin-like growth factors (IGFs), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF), will be discussed. Of the different vasoactive factors that play a role, mainly the renin-angiotensin system (RAS) and angiotensin II (Ang II) have been reported, and recent data on the importance of endothelin (ET) will be discussed. Other factors influencing diabetic kidney disease will be mentioned in brief. An introduction to each system will be given, followed by the changes found in the diabetic kidney, supported by evidence from both in vitro, and in vivo (animal and clinical) studies. The known interactions and links between different pathways will be mentioned, as well as potential treatment strategies targeting the specific pathways.
