Oxidative stress and increased expression of growth factors in lesions of failed hemodialysis access

The pathological role of oxidative stress in patients treated by hemodialys is has gained increasing recognition in recent years. Because complications related to vascular access are a major source of morbidity, immunohistoche mical evidence of oxidative stress and activation of growth factors were ex amined in native arteriovenous (AV) fistulae (n = 11) and expanded polytetr afluoroethylene (ePTFE) grafts (n = 15) recovered from hemodialysis patient s at the time of surgical revision or resection. To show the presence of ox idative stress in tissues, three markers were chosen: N-epsilon(carboxymeth yl)lysine, a structurally identified advanced glycation end product; 4-hydr oxy-2,3-nonenol, a lipid peroxidation product; and redox-active transition metals bound to proteins, a source of Fenton chemistry-generated free radic als. Markers of cell growth and proliferation were endothelin-1 (ET-1), a p otent mitogenic peptide implicated in the formation of intimal hyperplasia; transforming growth factor-beta (TGF-beta), a stimulus to vascular cell gr owth and matrix production; and platelet-derived growth factor (PDGF), a me diator of intimal hyperplasia. All specimens studied showed significant int imal hyperplasia. In general, the neointima close to the vascular lumen of the AV fistula and the pseudointima close to the lumen of the ePTFE graft w ere positive for oxidative stress markers. At sites of injury, especially i n the presence of histological evidence of inflammation and healing, expres sion of oxidative markers was particularly intense. Prominent staining of P DGF was shown at sites of anastomotic hyperplasia and in neovasculature. TG F-beta was associated with proliferation or repair in both AV fistulae and ePTFE grafts. ET-1 staining was most intense in the neointima and pseudoint ima. This study showed histochemical colocalization of markers of oxidative stress with growth factors known to contribute to intimal hyperplasia. (C) 2001 by the National Kidney Foundation, Inc.