By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with alemtuzumab than with conventional therapy. The apparent superiority of alemtuzumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, alemtuzumab and rabbit antithymocyte globulin had similar efficacy. (Funded by Astellas Pharma Global Development; INTAC ClinicalTrials.gov number, NCT00113269.).

Background Arteriovenous fistulas (AVF) for hemodialysis frequently fail to mature due to inadequate dilation or early stenosis. The pathogenesis of AVF non-maturation may be related to preexisting vascular pathology: medial fibrosis or micro-calcification may limit arterial dilation, and intimal hyperplasia may cause stenosis. Study design Observational study. Setting & Participants Chronic kidney disease patients (N=50) undergoing arteriovenous fistula (AVF) placement. Predictors Medial fibrosis, microcalcification, and intimal hyperplasia in arteries and veins obtained during AVF creation. Outcome and Measurements AVF non-maturation. Results AVF non-maturation occurred in 38% of patients despite attempted salvage procedures. Preoperative arterial diameter was associated with upper arm AVF maturation (p=0.007). Medial fibrosis was similar in patients with non-maturing and mature AVFs (60±14 vs 66±13%, p=0.2). AVF non-maturation was not associated with patient age or diabetes, even though both variables were significantly associated with severe medial fibrosis. Conversely, AVF non-maturation was higher in females than males, despite similar medial fibrosis in both sexes. Arterial micro-calcification (assessed semi-quantitatively) tended to be associated with AVF non-maturation (1.3±0.8 vs 0.9±0.8, p=0.08). None of the arteries or veins obtained at AVF creation had intimal hyperplasia. However, repeat venous samples obtained in 6 patients during surgical revision of an immature AVF exhibited venous neointimal hyperplasia. Limitations Single center study. Conclusion Medial fibrosis and micro-calcification are frequent in the arteries used to create AVFs, but do not explain AVF non-maturation. Unlike previous studies, intimal hyperplasia was not present at baseline, but developed de novo in non-maturing AVFs.

These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.

Significant mortality is associated with posttransplant lymphoproliferative disorder (PTLD) in kidney transplant recipients (KTX). Univariate/multivariate risk factor survival analysis of US PTLD KTX reported to Israel Penn International Transplant Tumor Registry from November 1968 to January 2000 was performed. PTLD presented 18 (median) (range 1-310) months in 402 KTX. Death rates were greater for those diagnosed within 6 months (64%) versus beyond 6 months (54%, p = 0.04). No differences in death risk for gender, race, immunosuppression, EBV, B or T cell positivity were identified. Death risk increased for multiple versus single sites (73% vs. 53%, hazards ratio (HR) 1.4). A 1-year increase in age increased HR for death by 2%. Surgery was associated with increased survival (55% vs. 0% without surgery) (p < 0.0001). Patients with allograft involvement, treated with transplant nephrectomy alone (n = 20), had 80% survival versus 53% without allograft removal (n = 15) (p < 0.001). Overall survival was 69% for allograft involvement alone versus 36% for other organ involvement plus allograft (n = 19 alive) (p < 0.0001). Death risk was greater for multiple site PTLD and increasing age, and risks were additive. Univariate analysis identified increased death risk for those not receiving surgery, particularly allograft involvement alone.