Role of Tumor Necrosis Factor Alpha in Disease Using a Mouse Model of Shiga Toxin-Mediated Renal Damage ▿

Mice have been extensively employed as an animal model of renal damage caused by Shiga toxins. In this study, we examined the role of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in the development of toxin-mediated renal disease in mice. Mice pretreated with TNF-α and challenged with Shiga toxin type 1 (Stx1) showed increased survival compared to that of mice treated with Stx1 alone. Conversely, mice treated with Stx1 before TNF-α administration succumbed more quickly than mice given Stx1 alone. Increased lethality in mice treated with Stx1 followed by TNF-α was associated with evidence of glomerular damage and the loss of renal function. No differences in renal histopathology were noted between animals treated with Stx1 alone and the TNF-α pretreatment group, although we noted a sparing of renal function when TNF-α was administered before toxin. Compared to that of treatment with Stx1 alone, treatment with TNF-α after toxin altered the renal cytokine profile so that the expression of proinflammatory cytokines TNF-α and interleukin-1β (IL-1β) increased, and the expression of the anti-inflammatory cytokine IL-10 decreased. Increased lethality in mice treated with Stx1 followed by TNF-α was associated with higher numbers of dUTP-biotin nick end labeling-positive renal tubule cells, suggesting that increased lethality involved enhanced apoptosis. These data suggest that the early administration of TNF-α is a candidate interventional strategy blocking disease progression, while TNF-α production after intoxication exacerbates disease

Percutaneous management of perianastomotic stenosis in arteriovenous fistulae: results of a prospective study

Surgical creation of new anastomosis has been proposed as the preferred treatment for perianastomotic stenoses of fistulae. However, disadvantages of surgical approach have included (1) frequent conversion of fistula to a graft by using synthetic graft material to create a new anastomosis, (2) shortening the length of the cannulation segment by proximal autologous arteriovenous neoanastomosis, and (3) abandoning the fistula altogether in favor of a synthetic graft. We report the results of a prospective study using percutaneous balloon angioplasty (PTA) to treat fistulae with perianastomotic lesions. Seventy-three consecutive patients undergoing 112 PTA procedures for the treatment of perianastomotic lesions were studied. Primary and secondary patency rates were calculated. Procedure success, procedure-related complications, and conversion of fistulae to grafts were recorded. The initial success rate was 97%. The degree of stenosis before and after PTA was 81 +/- 9 and 11+/-11%, respectively. Primary patency rates at 6, 12, and 18 months were 75, 51, and 41%, respectively. Secondary patency rates at 6, 12, and 18 months were 94, 90, and 90%, respectively. Grade I hematoma occurred in three and vein rupture in two cases. No grafts were inserted. These outcomes are superior to those that have been reported for surgery. The outpatient PTA is safe and effective for the management of perianastomotic stenosis. Because of its advantage of fistula preservation, the percutaneous approach should be considered as the preferred first-line therapy for the management of perianastomotic fistula lesions