Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model

Xenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibodies are an important component of the xenogeneic immune response. To address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody levels. We then selected animals with both low and high titers of anti-pig antibodies to proceed with kidney transplant from galactose-α1,3-galactose knockout/CD55 transgenic pig donors. All animals received T-cell depletion followed by maintenance therapy with costimulation blockade (either anti-CD154 mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high titer of anti-pig antibody rejected the kidney xenograft within the first week. Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days, respectively). Long-term surviving animals treated with the anti-CD154-based regimen continue to have normal kidney function and preserved renal architecture without evidence of rejection on biopsies sampled at day 100. This description of the longest reported survival of pig-to-non-human primate kidney xenotransplantation, now >125 days, provides promise for further study and potential clinical translation

Laparoscopic Incisional Hernia Repair After Solid-Organ Transplantation

Hypothesis: Laparoscopic incisional hernia repair (LIHR) is efficacious in transplant recipients. Design: Retrospective review. Setting: University hospital. Patients: Thirty-one transplant recipients who underwent LIHR between July 9, 2004, and October 27, 2005. Main Outcome Measures: Operative complications and incisional hernia recurrence. Results: The mean (SD) mesh size required for LIHR was 611 (307) cm(2). Median (range) hospital stay was 4 (1-28) days, with follow-up of 589 (22-953) days. Eighteen patients developed a postoperative complication, most frequently seroma formation, which occurred in 13 patients (72%). The mesh size required for LIHR was significantly larger in patients with a postoperative complication (n=18; 706 [319] cm(2) vs n=13; 480 [244] cm(2); P=.04). Seroma formation was not associated with previous open hernia repair, diabetes mellitus, or corticosteroid use. No statistically significant relationship was noted between the transplanted organ and seroma development. There were no post-LIHR wound infections. In 7 patients (23%), hernia recurred. Conclusions: Laparoscopic incisional hernia repair in solid-organ transplant recipients is associated with a high rate of seroma formation but minimal long-term morbidity. The recurrence rate after LIHR is equivalent to that after open hernia repair. These results suggest that LIHR is a safe and effective alternative to open repair in this patient population