BACKGROUND Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity. METHODS We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates. RESULTS At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole–aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups. CONCLUSIONS Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)

ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications. We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, (P = .03 compared with pretransplantation pre-TPE 1 6 ) . ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression. Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection. The risk of antibody-mediated rejection in ABO-incompatible kidney transplant recipients can be reduced by the pretransplantation removal of anti-A or anti-B isohemagglutinins using total plasma exchange (TPE) or immunoadsorbent columns, splenectomy, and quadruple l Although the liver seems to be more resistant to hyperacute rejection than the kidney and the heart, hyperacute rejection of the liver has been shown in presensitized recipientsI2-l4 and in recipients of ABO-incompatible liver allografts.15-'7 Antibody-mediated rejection also leads to an increased risk of vascular and biliary tract complications, leading to a markedly increased failure rate of ABO-incompatible liver allografts.18-20 Improvements in patient and graft survival rates have been achieved with perioperative TPE and quadruple immunosuppression, but antibody-mediated rejection and graft loss has not been eliminated.21Since 1992, we have used a protocol in ABO-incompatible liver transplant recipients based on the data from ABO-incompatible kidney transplantation.6-10 This includes pretransplantation TPE to remove anti-A and anti-B isohemagglutinins; posttransplantation TPE to maintain low titers for 2 weeks posttransplanl (Jdnuay,), 2003: pp [22][23][24][25][26][27][28][29][30]

Tumor necrosis factor-alpha ("Fa), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNFa in the pathogenesis of endotoxin-induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague-Dawley rats received either intravenous (IV) endotoxin (7.5 mgkg) or monoclonal anti-TNFa antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2-hour period, after which all animals received an lV bolus of taurocholate (10 pmoU100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti-TNFa antibody blocked this endotoxinassociated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 pg/mL) or TNFa (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose-and timedependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNFa is an important mediator of the cholestasis of sepsis. (HEPATOLOGY 1995;22:1273-1278.) Tumor necrosis factor-alpha (TNFa) is a cytokine that is released by macrophages, endothelial cells, and Kupffer cells, and is an important mediator of the inflammatory response. This cytokine is capable of diverse and extensive effects in many biological systems, and both the immunologic and metabolic effects have .4bbreviations: TNFcr, tumor necrosis factor-alpha; HPLC, high-performance liquid chromatography; DPBS, Dulbecco's phosphate-buffered saline; IV, intravenous; V,,, , maximal uptake velocity.

Existing policy is likely to be in the best interests of only certain sets of patients awaiting cadaveric kidney transplantation unless ECDs dramatically reduce expected waiting for transplantation. This is most possible in elderly patients because of the short wait-time reduction required to make ECDs beneficial. Data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. The data and analyses reported in the 2001 Annual Report of the United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients have been supplied by the United Network for Organ Sharing and University Renal Research and Education Association under contract with Health and Human Services. The authors alone are responsible for reporting and interpreting of these data.