Growth factors in the pathogenesis of diabetic nephropathy

Despite the growing toll of diabetic nephropathy on public health [1], the current armamentarium for treatment and prevention of the disease remains limited to the blocking of the renin-angiotensin-aldosterone system (RAAS) and the control of hyperglycemia. A number of large clinical trials attest to the effectiveness of such a treatment methodology [2, 3]. Yet recent evidence seems to show that a subset of patients continue to progress in their disease even with treatment [4, 5]. While the progression of nephropathy may be the result of incomplete patient adherence to therapeutic guidelines, this can also be viewed as a sign that the inhibition of the RAAS may not be equally efficient in all individuals. A number of additional therapies have been investigated over the past few years with no solid leads so far [6]. Growth factors have been associated with the development and progression of diabetic kidney disease (see Table 1). Understanding the role of these factors could generate future targets for therapy. In this chapter we will bring forth the current evidence and hypotheses on a number of these growth factors, focusing mainly on Transforming Growth Factor-beta (TGF-β) and the Vascular Endothelial Growth Factor (VEGF), the main players in the pathogenesis of the manifestations of diabetic nephropathy.