No abstract

While the incidence of antibody-mediated kidney graft rejection has increased, the key cellular and molecular participants underlying this graft injury remain unclear. Rejection of kidney allografts in mice lacking the chemokine receptor CCR5 is dependent on production of donor-specific antibody. Here we determine if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in these recipients. Wild type C57BL/6, B6.CCR5−/− and B6.CD8−/−/CCR5−/− mice were transplanted with complete MHC mismatched A/J kidney grafts and intra-graft inflammatory components were followed to rejection. B6.CCR5−/− and B6.CD8−/−/CCR5−/− recipients rejected kidney allografts by day 35 whereas 65% of allografts in wild type recipients survived past day 80 post-transplant. Rejected allografts in wild-type C57BL/6, B6.CCR5−/− and B6.CD8−/−/CCR5−/− recipients expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of donor-specific antibody. High levels of perforin and granzyme B mRNA expression peaked on day 6 post-transplant in allografts in all recipients, but were absent in isografts. Depletion of natural killer cells in B6.CD8−/−/CCR5−/− recipients reduced this expression to background levels and promoted the long-term survival of 40% of the kidney allografts. Thus, natural killer cells have a role in increased inflammation during antibody-mediated kidney allograft injury and in rejection of the grafts.

We have reported that B6.CCR5−/− mice reject renal allografts with high serum donor-specific antibody (DSA) titers and marked C4d deposition in grafts, features consistent with AMR. B6.huCD20/CCR5−/− mice, where human CD20 expression is restricted to B cells, rejected A/J renal allografts by day 26 post-transplant with DSA first detected in serum on day 5 post-transplant and increased thereafter. Recipient treatment with anti-huCD20 mAb prior to the transplant and weekly up to 7 weeks post-transplant promoted long-term allograft survival (> 100 days) with low DSA titers. To investigate the effect of B cell depletion at the time serum DSA was first detected, recipients were treated with anti-huCD20 mAb on days 5, 8 and 12 post-transplant. This regimen significantly reduced DSA titers and graft inflammation on day 15 post-transplant and prolonged allograft survival > 60 days. However, DSA returned to the titers observed in control treated recipients by day 30 post-transplant and histological analyses on day 60 post-transplant indicated severe interstitial fibrosis. These results indicate that anti-huCD20 mAb had the greatest effect as a prophylactic treatment and that the distinct kinetics of DSA responses accounts for acute renal allograft failure versus the development of fibrosis.

Objective: The standard protocol of antibiotic prophylaxis in radical prostatectomy remains to be established. We retrospectively compared the occurrence of perioperative infections following radical prostatectomy between two different protocols of antibiotic prophylaxis. Methods: This study included 106 cases of radical retropubic prostatectomy managed on the clinical pathways. Two different protocols of antibiotic prophylaxis were used in otherwise identical pathways. Between January and December 2004, 50 patients received a second generation cephem, cefotiam, for 4 days, beginning 30 min before surgery (4-day group), whilst between December 2004 and July 2005, only two doses of cefotiam were given on the day of operation in 56 patients (1-day group). The incidence of surgical site infection (SSI) and remote infection (RI) was retrospectively investigated. Results: Superficial incisional SSI occurred in one (1.8%) patient in the 1-day group, whereas no patient in the 4-day group developed SSI. No RI was observed in either the 1-day or 4-day group. Intravenous antibiotics were administered besides the pathway in a patient in the 1-day group because unexplained fever more than 38°C continued postoperative day (POD) 2 through POD 4 without signs of SSI or RI. Excluding this case, postoperative more than 38°C was rare and transient after POD 2. Conclusion: The incidence of SSI and RI was low and not significantly different between the 1-day and 4-day groups. Therefore, the 1-day protocol of prophylactic antibiotic treatment seems adequate for preventing perioperative infections in radical prostatectomy.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.