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Delayed graft function (DGF) in kidney transplantation affects adverse outcomes. It remains unclear whether the post-transplant dialysis modality alters perioperative or long-term graft outcomes. We performed a retrospective observational quality initiative at two Canadian renal transplant centers, in which DGF occurred in the recipient, necessitating one of peritoneal dialysis (PD) or hemodialysis (HD). There was no difference in baseline factors between patients with post-transplant PD (n = 14) or HD (n = 63). The use of PD was associated with an increased risk of wound infection/leakage (PD 5/14 vs. HD 6/63, p = 0.024), shorter length of hospitalization (13.7 vs. 18.7 d, p = 0.009) and time requiring dialysis post-operatively (6.5 vs 11.0 d, p = 0.043). There were no differences in readmission to hospital within 6 months (4/14 vs. 23/63, p = 0.759), graft loss (0/14 vs. 2/63, p = 1.000) or acute rejection episodes (1/14 vs. 4/63, p = 1.000) at one yr, and GFR did not differ between the PD or HD groups at 30 d (35.7 vs. 33.8 mL/min/m(2), p = 0.731), six months (46.9 vs. 45.5 mL/min/m(2), p = 0.835) or one yr (46.6 vs. 44.5 mL/min/m(2), p = 0.746). Further research is needed to determine which transplant patients are most appropriate to undergo PD catheter removal at the time of transplantation.

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BACKGROUND: Increased awareness of organ donation/transplantation has been found to have a positive influence on organ donation rates. One Life … Many Gifts is a curriculum resource in Ontario, Canada, to educate and raise awareness for senior secondary school students about the importance of organ and tissue donation and transplantation. Teachers administered pre- and post- attitudinal surveys to senior secondary school students to evaluate changes in their attitudes toward organ and tissue donation and transplantation. In this study, the effect of the One Life … Many Gifts educational intervention on changing the attitudes and awareness of organ donation and transplantation of senior secondary students was assessed. METHODS: Mann-Whitney U tests were used to compare the pre- and post-surveys as a whole and then again for the data from individual schools. Kruskal-Wallis H-tests were used to compare data between schools. RESULTS: A total of 1832 pre- and 1440 post-educational surveys returned to Trillium Gift of Life Network were assessed in the 2008-2009 academic year. Overall, comparison of all pre- and post-educational program survey data showed significant improvement in the students' attitudes toward organs and tissue donation and transplantation (P = .00625). CONCLUSION: The One Life … Many Gifts program made an impact on changing the attitudes toward and awareness of organ donation among high school students in Ontario. Evaluation of its impact on donor registration and organ donation among the students and their parents is complex and remains to be seen.

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The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound-guided kidney biopsies were performed. During that time, four recipients developed acute oligo-anuria following ultrasound-guided allograft biopsy. Emergent doppler-ultrasounds were performed demonstrating absence of diastolic flow as well as a sub-capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody-mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.

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BACKGROUND: In North America, the urological community has embraced surgical robotic technology in the performance of complex laparoscopic surgery. The performance of complex long-distance telesurgery requires further investigation prior to clinical application. METHODS: The feasibility of laparoscopic robot-assisted pyeloplasty in a porcine model was assessed using the Zeus robot and the internet protocol virtual private network (IP-VPNe) and satellite links. Eighteen pyeloplasty procedures were performed, using real-time, IP-VPNe and satellite network connection (six of each). Network and objective operative data were collected. RESULTS: Despite network delays and jitter, it was feasible to perform the pyeloplasty procedure without significant detriment in operative time or surgical results compared with real-time surgery. CONCLUSION: The completion of complex tasks such as robotic pyeloplasty is feasible using both land-line and satellite telesurgery. However, the clinical relevance of telesurgery requires further assessment.

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Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

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CD45RB monoclonal antibody (mAb) therapy is capable of prolonging allograft survival. We have previously shown that CD45RB mAb enriches the CD45RBlo T-cell population in vitro and in vivo by preferentially depleting CD45RBhi T cells. The present study assessed the importance of CD45RBhi T-cell depletion in murine cardiac allograft survival by infusion of naive CD45RB T-cell subsets. Here we show that naturally occurring CD45RBloCD4+ T cells express regulatory transcription factor Foxp3 and have regulatory function, whereas CD45RBhiCD4+ T cells express low levels of Foxp3 and have effector function. Infusion of syngeneic CD45RBhi T cells significantly reduced graft survival after depletion of CD45RBhi T cells by CD45RB mAb. Reduction of graft survival also occurred when syngeneic CD45RBhi T cells were infused into rapamycin-treated mice, whereas survival was prolonged when CD45RBlo T cells were added. This indicates that an alteration in the balance between regulatory CD45RBlo and effector CD45RBhi T cells is critical to the immunologic function of CD45RB mAb. A strategy to eliminate effector T cells with consequent enrichment of the regulatory T-cell compartment may be an important new strategy in the prevention of rejection.

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We reviewed the outcomes of pediatric en bloc renal transplantation at two Canadian centers in the cyclosporine era. Between 1984 and 2002, 16 patients received pediatric en bloc renal transplants. Mean recipient age and weight were 45 +/- 17 years and 72.2 +/- 14.4 kg, respectively. En bloc kidneys were procured from donors aged 2.1 +/- 0.8 years (range, 0.7 to 4.0), weighing an average of 14.3 +/- 2.0 kg (range, 12 to 17). All en bloc kidneys were successfully transplanted without thrombosis. All patients received calcineurin inhibitors and corticosteroids. Only three patients received antibody-based induction therapy. Rejection episodes occurring in seven grafts were all successfully treated. Mean follow-up was 3.7 years (range 0.4 to 15.0). Mean serum creatinine values at 3 months and 1 and 3 years were 138.8 +/- 54.5 micromol/L, 118.6 +/- 38.1 micromol/L, and 95.1 +/- 24.4 micromol/L, respectively. The mean creatinine value of five patients with at least 5 years follow-up was 96.8 +/- 12.3 micromol/L. Three-year graft and patient survival rates were 94%. Two deaths with functioning grafts occurred secondary to cardiac and infectious etiologies. None of the grafts were lost independent of death. We conclude that en bloc transplantation has excellent short- and long-term results. Improving graft function after 3 years represented by reduced serum creatinine suggests that these kidneys have excellent renal reserve and growth potential.

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Renal allograft compartment syndrome (RACS) is an underreported and poorly described surgical complication of renal transplantation. It occurs when a tight fascial closure compresses the graft in its limited retroperitoneal space. Without early recognition and reexploration, graft loss is inevitable. We describe a technique using a polypropylene mesh fascial closure (MHFC) to prevent and treat RACS. MHFC was performed primarily to prevent RACS and secondarily to treat this complication. Between April 2001 and October 2002, 16 patients undergoing 17 renal transplants underwent MHFC. Mean recipient body weight was 17% less than the mean donor weight. Mean follow-up was 9 months. Mean serum creatinine after primary MHFC was 148.4 micromol/L. Three of four patients with RACS regained function following secondary MHFC and had a mean serum creatinine of 155.3 micromol/L. Wound complications were seen in 5 (31%) with no wound or mesh infections and one patient was diagnosed with a lymphocele. We conclude that MHFC can be safely performed after kidney transplantation to prevent or treat RACS.

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BACKGROUND: Despite the recent advances in immunosuppression, steroid-resistant rejection remains a difficult problem in renal transplant recipients. METHODS: We reviewed our experience with i.v. immunoglobulin (IVIG) in the treatment of steroid- and antilymphocyte antibody-resistant rejection in renal transplant patients. Between September 1996 and March 1999, 17 patients were treated with IVIG to reverse steroid- or antilymphocyte antibody-resistant rejection. A total of 2 g/kg of IVIG was administered to patients during each treatment course. RESULTS: With a mean follow-up of 21.5+/-9.5 months from the time of IVIG administration, patient and graft survival rates were 94% (16/17) and 71% (12/17), respectively. The baseline mean serum creatinine level prior to rejection was 2.2+/-0.7 mg/dl and peaked at 3.3+/-1.1 mg/dl at the time of the diagnosis of refractory rejection. IVIG therapy was associated with a fall in the mean creatinine to 2.8+/-1.1 mg/dl. The most recent serum creatinine in patients with functioning grafts was 2.8+/-1.6 mg/dl. In 82% of allograft biopsies after IVIG, reversal or reduction in the severity of rejection was demonstrated. In addition, IVIG therapy rescued three of four patients with antilymphocyte antibody-resistant rejection. CONCLUSIONS: IVIG rescue therapy for steroid- or antilymphocyte antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival.

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Currently, lifelong immunosuppression is required for organ transplant recipients. The majority of transplant recipients will eventually develop chronic rejection with resultant graft loss, despite treatment with powerful immunosuppressive agents. These agents are also associated with numerous toxicities including reduced immunity against infection and malignancy. Therefore, the central goal in transplant science is to devise tolerance strategies in an attempt to establish a state of prolonged non-reactivity against the allograft, accompanied with preservation of an intact immune system. Although predictable tolerance induction has been elusive, we found that short course of the novel immunomodulatory agent, anti-CD45RB monoclonal antibody, leads to indefinite acceptance of renal allografts in mice, and has been shown to markedly prolong allograft survival in primates. We review the current state of development of this antibody, and the progress made in defining its mechanism of action.

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Over the past 3 decades, renal allograft survival has improved significantly as a result of the development of powerful immunosuppressive agents. Nevertheless, the overall half-life of renal allografts has increased marginally during that time period, owing to drug-related nephrotoxicity and chronic rejection. New immunosuppressive agents are being evaluated because of the need for a reduction in the dose of nephrotoxic calcineurin inhibitors and corticosteroids. Additional agents have demonstrated the ability to retard the onset of chronic rejection in preclinical transplant models. In concert with these efforts, approaches are in development to alleviate the ever increasing shortage of donor organs, including the as yet unrealized goals of successful and practical xenotransplantation and the bioartificial kidney. Further identification and development of novel agents that target the specific components of the allograft response will provide the key to the achievement of donor-specific tolerance, the "Holy Grail" of solid organ transplantation.

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Immature dendritic cells (DCs) are deficient in surface co-stimulatory molecules and have been shown to exhibit a 'tolerogenic' potential. We investigated the allostimulatory activity of immature DCs in one-way mixed leukocyte reactions and their capacity to inhibit anti-donor cytolytic activity in the sponge matrix allograft model. Immature DCs (CD80 and CD86 deficient) were derived from bone marrow cells propagated in GM-CSF and TGF-beta1. Mature DCs (CD80+ and CD86+) were derived from bone marrow cells propagated in GM-CSF and IL-4. Either 2 x 10(6) DBA/2J (DBA, H-2d) immature DCs or 2 x 10(6) mature DCs were injected intravenously into C57BL/6J (B6, H-2b) mice 7 days prior to sponge matrix allograft implantation. On day 12, the sponge was harvested and the graft-infiltrating cells were tested in vitro for cytotoxic T lymphocyte (CTL) activity. Immature dendritic cell (DC) infused significantly and markedly inhibited intra-graft CTL activity compared to mature DCs and syngeneic bone marrow control cells. The administration of immature DCs directly into the sponge allograft failed to induce hyporeactivity. Thus, the only systemic infusion of immature donor DCs was able to recapitulate the donor-specific transfusion effect, and the capacity of donor bone marrow cells to induce donor-specific hyporeactivity in the sponge allograft model.

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BACKGROUND: Donor-specific blood transfusion (DST) may improve allograft survival in human and animal models, but the mechanisms for this graft protective effect are incompletely understood. The sponge matrix allograft model was used to determine if DST induces regulatory factors within the allograft. METHODS: C57BL/6 (H-2b) recipients received donor-specific (DBA/2J, H-2d) or syngeneic (C57BL/6) blood 7 days before sponge matrix allograft (DBA/2J) implantation. Fourteen days postgrafting, the sponge infiltrating cells (SIC) were examined for cytotoxic T cell (CTL) and natural killer (NK) activity, and sponge exudate fluid (SEF) was assessed for nitric oxide (.N=O) and prostaglandin E2 (PGE2) content. Interleukin- (IL) 2, IL-4, IL-10, and interferon-gamma (IFN-gamma) production by SIC was also determined. Recipient splenocytes were simultaneously assessed for anti-donor cytotoxic and proliferative responses and .N=O production. RESULTS: SIC from mice receiving syngeneic transfusions (ST) acquired both CTL and NK activity postgrafting, with maximal activity by day 14. DST suppressed both CTL and NK activity throughout the postgrafting period. Limiting dilution analysis (LDA) of SIC to determine precursor and native CTL frequency showed significantly lower responder cell frequency after DST compared with ST. SEF .N=O levels and SIC production of IL-2 and IFN-gamma in grafted DST mice were significantly lower than in grafted mice receiving ST. No significant amounts of IL-4 and very low levels of IL-10 were produced by SIC from grafted mice after either ST or DST. Conversely, PGE2 content of sponge fluid and serum from DST mice was higher than in mice receiving ST. Antigen stimulated splenocyte proliferation and CTL development assessed by LDA were also inhibited by DST. CONCLUSIONS: Reduction in local TH1 cytokines, absence of detectable TH2 cytokines, with enhanced PGE2 and depressed .N=O were observed in the local graft environment after DST. These data support the hypothesis that DST induces donor-specific intragraft suppressor factors, accompanied by reduced local and systemic immune activation.

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