Role of anti-TGF-beta antibodies in the treatment of renal injury

Abstract

Chronic kidney diseases are emerging world wide as a public health problem. Finding more effective renoprotective therapies is a major challenge in nephrology. Soon after the discovery of transforming growth factor-beta (TGF-beta), it became clear that this cytokine is widely expressed in almost all kidney cells. Overexpression of TGF-beta isoforms and their receptors in the kidney of experimental animals is closely linked to renal fibrosis, a characteristic feature of progressive proteinuric nephropathies. Antibodies to TGF-beta halt the development of diabetic and non-diabetic nephropathies. The effect is maximized by the addition of TGF-beta antibodies on a background of angiotensin II blockade. Several studies have pointed to a role for TGF-beta in instigating the fibrotic process characteristic of progressive human glomerulopathies, although the possible benefit of selective inhibition of TGF-beta has not been described so far. This chapter discusses the role of TGF-beta in renal fibrosis, and describes the renoprotective potential of strategies that interfere with TGF-beta production in the kidney in experimental animals, as a new anti-fibrotic therapeutic approach.