Regeneration of kidney tubular epithelial cells

Conclusion The mechanisms that regulate regeneration of kidney epithelial cells after acute tubular necrosis are poorly understood. Repair of the nephron can take place in the adverse systemic metabolic setting caused by failure of renal function. This clinical observation suggests that factors released at the site of the tubular insult can mediate repair. Studies carried out in this and other laboratories show that kidney epithelial cells can release and respond to polypeptide growth factors which may thereby contribute to renal regeneration by autocrine and paracrine mechanisms. Specific growth factors secreted by cells and deposited in the tubular basement membrane prior to injury may subsequently participate in nephron repair. In addition, adenine nucleotides released from injured or dying cells at the injury site or provided exogenously could stimulate surviving renal epithelial cells at the edges of the wound to migrate along the basement membrane to rapidly reepithelialize the nephron and subsequently initiate mitogenesis to replace cells lost by necrosis.The nephrotoxic effect of many agents used in cancer chemotherapy and the older age of patients undergoing complicated surgical procedures has increased the incidence of ARF, whereas the mortality rate has not changed since the early 1950s 22]. Thus there is considerable need for innovative therapeutic strategies. An important goal of future research efforts is to identify new growth factors that facilitate migration, differentiation, and proliferation of renal epithelial cells at sites of tubular necrosis. Isolation and use of these agents in combination with dialysis and nutritional support could speed renal regeneration and thereby improve the outcome in patients with this condition.Abbreviations ARF acute renal failure - ECM extracellular matrix - EGF epidermal growth factor - FGF fibroblast growth factor - IGF insulin-like growth factor - MGSA melanocyte growth-stimulating activity - PDGF platelet-derived growth factor - IGF transforming growth factor