Rates Of Acute Cellular Rejection Research Articles

Evolving concepts in the selection of immunosuppression regimen for liver transplant recipients.

The introduction of calcineurin inhibitor (CNI) based immunosuppression has revolutionized the field of liver transplantation by dramatically reducing the incidence of acute cellular rejection and prolonging patient and allograft survival. However, the introduction of CNIs has also come at the price of increased patient morbidity, particularly with regard to the well-known nephrotoxic effects of the medications. In an effort to minimize the adverse effects, immunosuppression regimen have evolved to include the use of various induction agents and purine synthesis inhibitors to limit the dose of CNI necessary to achieve low acute cellular rejection rates. Careful assessments of risks and benefits are needed as these newer agents have their own side effect profiles. In addition, the impact of newer immunosuppression regimen on hepatitis C (HCV) recurrence has not been completely elucidated. This review will provide an overview of the most common immunosuppression regimen used in liver transplantation and discuss their impact on acute cellular rejection, patient and allograft survival, and HCV recurrence.

Association of lymphocyte crossmatch and the outcome of intestinal transplantation in swine

The effect of preformed antidonor antibodies have been demonstrated in various types of solid organ transplantation. However, the significance of anti-donor antibodies in intestinal transplantation remains unclear. The aim of this study is to evaluate the impact that the extent of T cell crossmatch has on the outcome of swine intestinal transplantation. All studies were performed on outbred domestic male pigs weighing from 15 to 20kg. Intestinal transplantation was performed orthotopically with an exchange of grafts between white and black pigs. FK506 was administered intravenously (0.1mg/kg per day, POD 0-7) for immunosuppression. A lymphocyte crossmatch test was performed using the direct CDC crossmatch. The results were considered positive when more than 10% of the donor lymphocytes were killed by the recipient's serum. In addition, 0-10, 11-20, 21-30, 31-80 and 81-100% of the killed lymphocytes were classified as grade 1, 2, 4, 6 and 8, respectively. A total of 34 intestinal transplantations were performed. All but one case had positive donor specific T cell crossmatches. The number of grade 2, 4, 6 and 8 cases was 11, 14, 6 and 2, respectively. Although there was a tendency towards a decreased survival according to the grade, the survival rate was not statistically different among each different grade. Moreover, the rates of acute cellular rejection and vascular complications were not significantly different among the four grades. These results suggest that the extent of positive T cell crossmatch is not associated with the outcome of swine intestinal transplantation.

Hepatitis C recurrence is not adversely affected by the use of donation after cardiac death liver allografts

Many factors can worsen a recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). We sought to determine whether the use of donation after cardiac death (DCD) livers affects HCV recurrence. From January 2000 to June 2008, 37 HCV patients underwent LT with DCD allografts. The outcomes and severity of HCV recurrence were analyzed along with those for 74 matched control patients with HCV who received donation after brain death (DBD) livers. The 2 groups had similar donor and recipient characteristics, immunosuppression regimens, rates of acute cellular rejection (ACR), and HCV profiles. DCD patients had a higher incidence of primary nonfunction (19% versus 3%, P = 0.006) and significantly higher peak aspartate aminotransferase levels in comparison with DBD subjects, suggesting a greater degree of ischemia/reperfusion injury. Although the survival rates were not significantly different, DCD recipients had lower 1- and 5-year patient survival rates (83% and 69% versus 84% and 78%, respectively, P = 0.75) and graft survival rates (70% and 61% versus 82% and 74%, respectively, P = 0.24). Three hundred fourteen protocol and clinically indicated liver biopsy procedures were performed within 6 years after transplantation, and mixed modeling analysis showed that fibrosis progression rates were similar for the 2 groups (0.6 fibrosis units/year according to the Ishak modified staging system). The rates of severe HCV recurrence (retransplantation or death due to recurrent hepatitis C and/or the development of stage 4/6 fibrosis or worse within 2 years) were similar [3 DCD patients (8%) versus 11 DBD patients (15%), P = 0.38], and cytomegalovirus infection (hazard ratio = 7.9, P = 0.002, 95% confidence interval = 2.1-28.9) and ACR (hazard ratio = 6.2, P = 0.002, 95% confidence interval = 2.0-19.7) were the only independent risk factors for severe recurrence. In summary, although there was a trend of poorer overall outcomes in DCD patients, the use of DCD livers did not appear to adversely affect HCV recurrence after LT.

Immunosuppressive Therapies in Solid Organ Transplantation

Background: Organ transplantation is a life saving procedure in patients with end-organ disease. While improvement in surgical techniques made transplantation possible in the 1960s, advances in immunosuppressive therapies have resulted in lower rates of acute cellular rejection and consequently, significant improvements in patient and graft survival after solid organ transplantation. Aim: To discuss all immunosuppressant medications in organ transplantation. These medications are potent, have substantial drug interactions, and have acute and chronic toxicities. Conclusion: Immunosuppressive protocols must be balanced not only to minimize graft rejection, but also to avoid complications related to adverse effects. Further studies are needed to optimize optimal use of these medications in relation with immune tolerance. This article provides a general overview of efficacies and toxicities of current immunosuppressive therapies. Keywords: Immunossuppression, organ transplantation, steroids, azathioprine, calcineurin inhibitors, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, anti-thymocyte globulin, OKT3, Basiliximab, Daclizumab, interleukin-2 antagonists

Pediatric living-donor liver transplantation for acute liver failure: analysis of 57 cases

We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto University Hospital in Japan over a period of 15 years to compare the etiology and the long-term outcome of infants and children after living donor liver transplantation (LDLT). Patients were divided into two groups according to age at the time of liver transplantation, infants group (<1 year, n = 20), and children group (1-18 years, n = 37). The overall survival rates were 73.6%, 69.5% and 67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the time of LDLT had a strong impact on their outcome, Children had significantly better outcome than infants (P = 0.001). Surgical complications were comparable between both groups. Infants had higher rates of acute cellular rejection (ACR), which was associated with features of hepatitis in many cases. Refractory ACR was the leading cause of death in eight out of 12 infants, while it resulted in loss of one child only. Cox's proportional hazard regression model was used to examine potential risk factors for graft loss and it shows that age <1 year was associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961-76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children and refractory ACR was the leading cause of death. Using additional immunosuppressant for cases with severe and atypical rejections is recommended.

Whole-Organ Pancreas Transplantation at Baylor Regional Transplant Institute: A Chance to Cure Diabetes

The success of pancreas transplantation has improved over the past several decades with advancements in surgical technique, immunosuppressive medicines, and immunologic testing. We retrospectively reviewed our experience with pancreas transplantation from 1995 to 2008. At the Baylor Regional Transplant Program, 151 pancreas transplants were performed in 147 patients: 135 were simultaneous pancreas-kidney transplants, 10 were pancreas transplants after kidney transplants, and 6 were pancreas transplants alone. Follow-up information was available for 138 patients. The 1-year acute cellular rejection rate was 31.6%; the 30-day surgical reexploration rate was 10%; and the technical failure rate was 5.3%. Five-year pancreas graft survival rates were 67% for simultaneous pancreas and kidney transplants and 50% for pancreas transplants after kidney transplants. These outcomes exceed expected results as calculated by the Scientific Registry of Transplant Recipients. In addition, the median time to transplant was 3.8 months, compared with a US median of 14.1 months. Pancreas transplantation is currently the closest thing to a cure for diabetes and should be given as an option for diabetic patients with or without end-stage renal disease.

Higher tacrolimus trough levels on days 2–5 post‐renal transplant are associated with reduced rates of acute rejection

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2-13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14-20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5-27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5-77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult-to-adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with >/=1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had >/=1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.

Simultaneous Monitoring by Real-Time Polymerase Chain Reaction of Epstein-Barr Virus, Human Cytomegalovirus, and Human Herpesvirus-6 in Juvenile and Adult Liver Transplant Recipients

Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) cause symptomatic diseases in liver transplant recipients. The loads of these viruses, the associations between viral DNAemia, serologic status, and acute rejection reactions were investigated in a group of 17 juvenile and 17 adult recipients of living donor liver transplantation (LDLT) for a median of 8 weeks posttransplantation. At least 1 plasma sample from 15/34 (44.1%) patients was positive for CMV DNA. For most of the CMV-positive patients, the CMV DNA appeared in the second week of LDLT, and disappeared by the eighth week. A minimum of 200 EBV DNA copies/μg peripheral blood mononuclear cell DNA (defined as positive for EBV) was detected in 5/34 (14.7%) patients, and the number of EBV-positive children was significantly greater than the number of EBV-positive adults. In most of the EBV-positive patients, the EBV loads increased after 4 weeks posttransplantation. Plasma HHV-6 was detected in 7/34 (20.6%) patients. HHV-6 DNA appeared for a short period from the second week of LDLT. In addition, 8 of the 19 virus-positive recipients carried 2 viruses, with the combination of CMV and HHV-6 being the most frequent. Serologic status seemed to be an important factor for all 3 viral infections. The rate of acute cellular rejection was not significantly higher in the CMV-, EBV-, or HHV-6-positive groups. Simultaneous monitoring for 3 herpesviruses revealed the impact of these viruses on LDLT recipients.

Basiliximab Versus Steroids in Double Therapy Immunosuppression in Liver Transplantation: A Prospective Randomized Clinical Trial

: Basiliximab (B), an anti-CD25 monoclonal antibody, may represent an alternative to steroids (S) in immunosuppression after liver transplantation (LTx). The aim of this prospective randomized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx. : Forty-seven adult recipients of LTx were randomly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7. Clinically suspected acute cellular rejection (ACR) was histologically confirmed. Endpoints include ACR, survival, and disease-free survival. : In group B (26 patients), there were seven biopsy-confirmed ACR with an ACR rate of 15.4%; in group S (21 patients), 8 ACR with an ACR rate of 28.6% (P=n.s.). Cumulative survival at 36 months after transplantation was 84.3% for group B and 61.0% for group S. In hepatitis C virus patients (n=20: 12 in group B, 8 in group S), the ACR rate was 25% in group B and 50% in group S. The incidence of infection and other adverse events was similar in the two treatment groups. : B may represent a valid alternative to S in the induction of immunosuppression in LTx. Further studies of basiliximab in a large cohort are needed.

Can Endoscopic Visualization Predict Histological Changes and Early Rejection of Small Intestine Grafts?

Purpose: Improvements in tolerogenic immunosuppressive therapy have resulted in major improvements in small bowel transplantation (SBTx) survival during the past decade, such that survival parallels that for liver transplant recipients: >90% for the first year. Although rejection may be more frequent with SBTx because of the immunogenic character of the intestine, it is easier to detect early acute cellular rejection (ACR) due to endoscopy, and if detected early, ACR is rapidly reversible with steroid bolus therapy. In the 1st yr following SBTx, a short segment of ileum is interconnected between the colon, ileal graft and abdominal wall that makes graft access easy. The objective of this study was to compare visual findings to histology from chimney biopsies in asymptomatic and to more invasive ileal and jejunal biopsies in symptomatic patients. Methods: We analyzed the single experience of an experienced endoscopist over 12 months. 590 surveillance graft ileoscopies and biopsies were performed in 67 stable asymptomatic patients (Table 1), and 40 combined ileoscopies and enteroscopies in 19 symptomatic patients. The surveillance microscopic findings were divided into 3 subcategories: mucosal architecture (normal vs. abnormal: e.g. distortion, ulceration, regeneration, granulation, atrophy), lamina propria inflammation (normal vs. abnormal: e.g. edema, congestion, hemorrhage, inflammatory infiltrate), and crypt apoptosis (normal <0–4 apoptotic bodies/10 HPF, abnormal ≥5).Table: Surveillance endoscopies.Results: In surveillance, the positive predictive value of visualization for normal histology was 83.5% for mucosal architecture, 34.3% for lamina propria, and 94.5% for apoptosis score. The predictive value of visualization for abnormal histology was 77.5% for mucosal architecture, 93.8% for lamina propria, and 33.8% for apoptosis score. The correlation between visualization and the microscopic findings was significant overall for the 3 variables (Pearson Chi-Square; P < 0.01). In symptomatic patients, ACR was detected in 24/40 endoscopies although the mucosa looked normal in 14. In 30 pts where chimney and ileal biopsies were taken, ACR was detected in 21, with 16 showing ACR in both sites and 4 ACR in the chimney alone. In 10 patients jejunal biopsies were taken in addition to chimney showing the same rate of ACR in both sites. This suggests a sensitivity of 94% for chimney biopsy detection of graft ACR. Conclusion: Although endoscopic visualization identifies most patients with abnormal histology, early features of ACR may be missed, making biopsy mandatory, even in high risk coagulopathic patients. The high sensitivity of chimney biopsy in detecting ACR endorses the priority of early, less invasive, chimney biopsy in the surveillance of SBTx patients.

Increased rejection rates in cardiac transplant associated with dexamethasone

Background Peri-operative immunosuppression in cardiac transplantation includes the use of intravenous methylprednisolone. During a national shortage, intravenous dexamethasone was substituted for methylprednisolone at standard equivalencies. Methylprednisolone and dexamethasone are used interchangeably in many clinical settings; however, their equivalency has not been demonstrated. Methods Forty-two consecutive cardiac transplant patients were studied retrospectively. All patients received standard triple immunosuppression. Eighteen patients received dexamethasone and 24 methylprednisolone. Twelve patients were included for comparison after the methylprednisolone shortage resolved. Endomyocardial biopsy (EMB) results graded as ≥1B (ISHLT classification) were considered positive for acute cellular rejection. Results More patients who received dexamethasone as induction had cellular rejection (12/17; (70%) vs. 14/33; (42%); p = 0.05). Four patients were excluded because of deaths unrelated to cardiac function. The increased rate of rejection seen during dexamethasone substitution declined after reinstitution of methylprednisolone ( p = 0.05). Conclusions Peri-operative high-dose dexamethasone in cardiac transplants was associated with higher rates of acute cellular rejection. The equivalencies of dexamethasone and methylprednisolone differ from accepted standards when used in pulse doses. Peri-operative use of glucocorticoids may rely on mechanisms that are different from those considered in the standard equivalency measures. Pulse doses of dexamethasone and methylprednisolone in transplantation may not be interchangeable at standard equivalencies.

Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.

A comparison of sirolimus vs. calcineurin inhibitor‐based immunosuppressive therapies in liver transplantation

Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Treatment of HCV recurrence: Do the pretransplantation rules apply?

Treatment of HCV recurrence: Do the pretransplantation rules apply?

Sirolimus Conversion After Liver Transplantation: Improvement in Measured Glomerular Filtration Rate After 2 Years

Methods We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125–labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. Results Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration ( P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. Conclusions Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.

Marked Differences in Acute Cellular Rejection Rates between Living-Donor and Deceased-Donor Liver Transplant Recipients

: Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients. : Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling. : Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05). : Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity.

Patient and graft outcomes following liver transplantation for sarcoidosis

End-stage liver disease as a consequence of hepatic sarcoidosis is a rare indication for liver transplantation. Consequently, there is a paucity of information on the pre-transplant findings and post-operative course of individuals transplanted for hepatic sarcoidosis. The purpose of this study was to evaluate our experience with liver transplantation for sarcoidosis. Cases were identified by review of the Mount Sinai Hospital liver transplant database. For each case, two control patients with other causes of liver failure matched for age, gender and date of transplant were selected for comparison. Hepatic sarcoidosis was the indication for liver transplantation in only seven of 2117 (0.3%) adult transplants performed from September 1988 to June 2004. The diagnosis of sarcoidosis was established by findings of extensive, non-caseating granulomas in pre-transplant liver biopsy specimens or in the native liver explant. Extrahepatic disease was limited to pulmonary involvement in four patients. Sarcoid cases were statistically more likely to have diabetes mellitus (100% vs. 21%, p = 0.001) and less likely to have antibodies to hepatitis C (0% vs. 50%, p = 0.047). Rates of acute cellular rejection were 57% in cases and 36% in controls (p = 0.397). Hepatic granulomas were identified in one patient at 5.6 yr of follow-up. Among cases, the 1-yr graft and patient survival rates were 100% and 5-yr graft and patient survival rates were 86%. The 1- and 5-yr graft and patient survival rates were comparable with those of patients transplanted for other indications.

Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.

MORBID OBESITY, AN INDICATION FOR LAPAROSCOPIC LIVING NEPHRECTOMY?

P155 Aims: Obesity historically has been viewed as complicating factor for laparoscopic surgeons. In addition to the technical challenges of positioning and instrumentation, it is often felt these patients have a propensity for postoperative and anesthetic complications. The benefit and safety of the laparoscopic nephrectomy has been demonstrated in numerous studies over the last 5 years. With the improved operating times and post operative care paths the ability for a living donor to donate a kidney has become safer with an improved risk/benefit ratio. Even so, the mean waiting time for a recipient patient on the cadaveric transplant kidney list continues to grow due to a relative deficiency of donor organs. Because of this the donor pool has been opened to include marginal cadaveric kidneys and living patients who may not be ideal candidates for donation due to factors other than kidney function. Many transplant programs have decreased the weight restrictions that they once had on living donors to fill part of this void. The aim of this investigation evaluates the outcomes between obese and non-obese living kidney donors after a hand-assisted laparoscopic nephrectomy. Methods: Living related and un-related donors underwent a hand-assisted laparoscopic nephrectomy between 10/1998 and 9/2003 at a single transplant program. Data was collected retrospectively from chart review. A BMI>32 was defined as obese. Results: 224 living kidney donors underwent laparoscopic donor nephrectomy; 43 patients had a BMI <32 and 179 >32. No statistical differences were found between obese and non-obese patients in estimated blood loss, length of stay, time to oral intake or time to solid food intake, creatinine clearance at 1, 7, or 90 days, mean urine output, pain medicine requirements or complications. Similarly no differences in warm or cold ischemic times were noted between obese and non-obese donors. Conclusions: The hand-assisted donor nephrectomy has been shown to be equal to the open technique in regards to complication rate, infections, function of the donor kidney, rates of acute cellular rejection in the recipient and the graft survival long term. Benefits of the laparoscopic technique include decreases in hospital length of stay, bowel dysfunction, complication rates, pain control and overall patient satisfaction. The results in this study indicate that the obese patient with a BMI >32 has equal outcomes to their non-obese counterparts when donating a kidney for transplantation and obesity should be an INDICATION for the laparoscopic harvest of donor kidneys and not a contraindication.