Rabbit Antithymocyte Globulin Induction Research Articles

Thymoglobulin Induction and Sirolimus Versus Tacrolimus in Kidney Transplant Recipients Receiving Mycophenolate Mofetil and Steroids

To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P<0.05). At month 12, patient survival and incidence of biopsy-proven rejection were not different between groups (95.8% vs. 97.1%, and 16.9% vs. 12.9%, respectively). However, proportion of graft loss was higher with SRL at months 6 and 12 (11.3% vs. 0.0%, P=0.004; 14.1% vs. 4.3%, P=0.044, respectively). Adverse events and premature withdrawals were more frequent with SRL (P<0.001 and P<0.05, respectively), whereas cytomegalovirus infections were more frequent with tacrolimus (P<0.001). Patients treated with induction plus SRL, mycophenolate mofetil, and corticosteroids may obtain good renal function but have a higher risk of adverse events, drug withdrawal, and graft loss.

A prospective, randomized, multicenter study evaluating early corticosteroid withdrawal with Thymoglobulin® in living‐donor kidney transplantation

This study compared the safety and efficacy of early corticosteroid withdrawal (ECSWD) with rabbit anti-thymocyte globulin (rATG) induction to chronic corticosteroid therapy (CCST) without antibody induction in primary, living-donor renal transplant recipients. Eligible subjects were randomized 2:1 to receive either an ECSWD (n = 103) or CCST (n = 48) regimen, with all subjects receiving tacrolimus and mycophenolate mofetil (MMF). Results are reported as ECSWD vs. CCST. No significant differences were observed in the primary composite endpoint of freedom from biopsy-proven acute rejection (BPAR), graft loss, and death at six months (85.4% vs. 85.4%) or 12 months (84.4% vs. 74.4%). At 12 months, no difference was observed in BPAR (13.9% vs. 19.4%); however, ECSWD was associated with lower total cholesterol (159.7 +/- 39.2 vs. 196.5 +/- 56.7 mg/dL, p = 0.012), and trends toward significance were noted in serum triglycerides (151.9 +/- 92.0 vs. 181.4 +/- 78.8 mg/dL, p = 0.073) and weight gain (+3.6 +/- 9.4 vs. +6.4 +/- 9.3 kg, p = 0.069). No differences were observed in serious adverse events or infectious complications, with the exception of a higher incidence of leukopenia with ECSWD. rATG with tacrolimus and MMF therapy may allow early elimination of corticosteroids, is associated with trends toward lower lipid levels, less weight gain, and a safety profile comparable to CCST therapy.

Thymoglobulin Induction Dosing Strategies in a Low-Risk Kidney Transplant Population: Three or Four Days?

The optimal dose and duration of rabbit antithymocyte globulin (rATG) induction has not been defined. Methods. We compared the safety and efficacy of 2 dosing strategies, rATG 1.5 mg/kg for 4 days (n = 59) versus 2 mg/kg for 3 days (n = 59), in a retrospective, cohort study. Results. Two-year rejection-free survival was 95% in each group (P = .983). Renal function and infection rates were similar. The incidence of leucopenia was similar, although the 2 mg/kg group was more likely to be thrombocytopenic on day 2 (4% versus 28%, P = .04). Length of stay tended to be longer for the 1.5 mg/kg group (6.0 ± 3.7 versus 5.1 ± 1.9 days P = .104). A cost savings of $920 per patient for rATG were seen in the 2 mg/kg group (P = .122). Conclusions. Shorter, more intense dosing of rATG is safe and effective. The 3-day dose strategy resulted in a clinically shorter length of stay and may result in cost savings.

Reduced Dose Rabbit Anti-Thymocyte Globulin Induction for Prevention of Acute Rejection in High-Risk Kidney Transplant Recipients

Despite the prevalent use of rabbit antithymocyte globulin (rATG) as an induction agent in kidney transplantation, the appropriate dose for preventing acute rejection in high-risk patients is not known. Few studies have examined total exposure of rATG less than 6 mg/kg, with fewer studies examining lower dose rATG in patients with increased risk factors for acute rejection. We retrospectively analyzed outcomes of 83 kidney transplant recipients at increased risk for acute rejection (repeat transplant, African American race, and panel reactive antibody > or =20%) from July 2004 to July 2007 who were treated with rATG 1.5 mg/kg per day for 3 (n=39) or 4 (n=44) doses for induction to determine the impact of reduced-exposure rATG in the prevention of acute rejection. rATG was initiated intraoperatively and continued on consecutive days. All patients received triple maintenance immunosuppression including prednisone and calcineurin inhibitor. Patients requiring dialysis within 48 hr after transplant were excluded from analysis. One-year acute rejection rates were 10% and 11% in the 3- and 4-dose cohorts, respectively, with 100% patient and graft survival at 1 year in both groups. Patients in the 3-dose cohort were discharged from the hospital sooner than the 4-dose cohort (median length of hospital stay, 3 vs. 4 days; P=0.004). Our results suggest that a 3- or 4-dose course of rATG (1.5 mg/kg/dose) provides excellent protection against acute rejection even in patients at increased risk, with the potential for cost savings from a reduction in hospital stay and medication administration.

Clinical and Economic Outcomes of Rabbit Antithymocyte Globulin Induction in Adults Who Received Kidney Transplants from Living Unrelated Donors and Received Cyclosporine‐Based Immunosuppression

To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. Retrospective cohort study. Large academic medical center. Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Serum Sickness After Treatment With Rabbit Antithymocyte Globulin in Kidney Transplant Recipients With Previous Rabbit Exposure

Serum sickness after rabbit antithymocyte globulin administration has a reported incidence of 7% to 27% in kidney transplant recipients. We describe 4 patients with previous exposure to rabbits who developed serum sickness after primary rabbit antithymocyte globulin induction. All patients presented with jaw pain. Three of 4 patients treated with plasmapheresis and steroids had prompt recovery, and 1 patient treated with steroids had slower recovery. We performed a telephone interview of 214 patients who contemporaneously underwent transplantation between November 2006 and July 2008 regarding rabbit exposure. More than half the patients had some type of previous rabbit exposure. There was a suggestion that patients with serum sickness were exposed more frequently to rabbits than those without. Jaw pain appears to be a hallmark symptom, and treatment with plasmapheresis and steroids relieves symptoms more rapidly than steroids alone.

Rabbit Antithymocyte Globulin Is More Beneficial in Standard Kidney Than In Extended Donor Recipients

In a randomized, international study comparing rabbit antithymocyte globulin (TMG) and basiliximab (BAS) induction in renal transplant recipients at risk for delayed graft function or acute rejection (n=278), TMG was associated with less acute rejection at 1 year. This study analyzed outcomes stratified by standard criteria donor (SCD), extended criteria donor (ECD), and hypertensive donor. Data-capture limitations necessitated defining ECD as donor age more than 60 years or 50 to 60 years with hypertension and renal insufficiency. Seventy-five recipients received ECD-kidneys (28.4% TMG vs. 25.6% BAS, P=NS) and 203 recipients received SCD-kidneys (72.6% TMG vs. 74.4% BAS, P=NS). Recipients of an ECD or hypertensive donor-kidney had similar outcomes between treatment groups. Recipients of an SCD-kidney treated with TMG had less rejection (odds ratio [OR] 0.48). Recipients of a normotensive donor-kidney treated with TMG had less rejection (OR 0.56). Recipients of a normotensive, SCD-kidney treated with TMG had less rejection (OR 0.47) and death (OR 0.17) than their counterparts treated with BAS. Contrary to its perceived niche in recipients of ECD-kidneys, TMG was most beneficial in patients who received a normotensive, deceased SCD kidney.

Oral ganciclovir versus valganciclovir for cytomegalovirus prophylaxis in high‐risk liver transplant recipients

This retrospective review compared oral valganciclovir (VGCV) 450 mg daily for 6 months versus oral ganciclovir (GCV) 1000 mg 3 times daily for 3 months in preventing cytomegalovirus (CMV) disease in high-risk liver transplant recipients.We evaluated all CMV donor positive-recipient negative liver transplant recipients managed at University Health System in San Antonio,Texas from August 1996 to September 2006. CMV disease was confirmed by polymerase chain-reaction or antigenemia assay, and CMV invasive disease by tissue biopsy. Patient demographics, laboratory results, complications, and therapies were collected via retrospective chart review. Patients < 18 years of age or those who died during transplant admission were excluded. Primary endpoints included incidence, onset, and severity of CMV disease up to 1 year post transplant. Data collection also included patient demographics, immunosuppression, CMV treatment regimens, and relevant lab results. A total of 64 patients (43 VGCV and 21 GCV) were identified. Four patients developed CMV disease:VGCV (3/43,7%) versus GCV (1/21, 5%) (P=1.0), with 1 VGCV patient experiencing tissue-invasive CMV. In all cases, onset of CMV disease occurred after prophylaxis was discontinued. Onset occurred at 24, 27, and 45 weeks post transplant in the VGCVgroup, and at 26 weeks in the 1 patient on GCV. Four patients received rabbit antithymocyte globulin (rATG) induction; 1 patient received rATG and developed CMV disease, with no statistical difference compared with the 3 remaining patients who received rATG but did not develop CMV disease (P=0.09). No difference was found in incidence of CMV disease between patients who received GCV and those who received VGCV at our institution.

The effect of rabbit anti-thymocyte globulin induction therapy on regulatory T cells in kidney transplant patients

Prevention of alloreactivity by rabbit anti-thymocyte globulins (rATG) may not only result from immunodepletion but also from the induction of T cells that control allogeneic immune responses. In the present prospective and controlled study, we investigated the effect of rATG on the frequency, function and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant (KTx) patients. After transplantation, 16 patients received ATG-induction therapy and triple therapy consisting of tacrolimus, MMF and steroids. The control group (n = 18) received triple therapy only. By flow cytometry, T cells were analysed for CD25, FoxP3, CD127, CD45RO and CCR7. To study their suppressive capacities, CD25bright T cells were co-cultured with CD25(-/dim) effector T cells (Teff) in mixed lymphocyte reactions (MLR), stimulated with donor and third party (3P) antigens. Pre-transplant levels of FoxP3+CD127(-/low) T cells were 6% of CD4+ T cells. One week post-ATG treatment, no measurable numbers of regulatory T cells were present (P < 0.01). After 4 weeks, the cell numbers of CD4+FoxP3+CD127(-/low) T cells slowly reappeared and thereafter remained low (P < 0.01). At 14 weeks, a significant shift towards the CD45RO+CCR7+ (central memory) phenotype within CD4+FoxP3+ T cells was observed (P < 0.01). At 26 weeks, the proliferative alloresponses of the PBMC and CD25(-/dim) Teff profoundly decreased compared to pre-transplant (P = 0.01 and P = 0.02 respectively), while the regulatory capacity of the CD25bright T cells, of which 90% consisted of FoxP3+CD127(-/low) T cells, remained unaffected. The CD25bright T cells suppressed the anti-donor (94%) and 3P responses (93%). Our findings show that rATG therapy does not spare peripheral immunoregulatory T cells in vivo, but after regeneration preserves their suppressive activity.

Excellent Renal Allograft Survival in Donor-Specific Antibody Positive Transplant Patients—Role of Intravenous Immunoglobulin and Rabbit Antithymocyte Globulin

Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Modern Approaches to Combining Sirolimus With Calcineurin Inhibitors

Routine renal transplantation maintenance immunosuppression at the University of Nebraska Medical Center consists of rabbit anti-thymocyte globulin (rATG) induction with early steroid withdrawal followed by maintenance with sirolimus and tacrolimus, a regimen we have used with >900 patients. Induction consists of 6 mg/kg rATG in 4 doses of 1.5 mg/kg each on days 0, 2, 4, and 6. Prednisone is used only in association with rATG administration. Maintenance agents are introduced gradually depending on renal function. Since April 2004, we have been conducting a prospective, randomized trial of this regimen versus 2 modifications: administering the rATG induction dose (6 mg/kg) in a single infusion over 24 hours; and, after 6 months, replacing tacrolimus with mycophenolate mofetil (MMF) in half of the study subjects. This study has shown several benefits of single-dose rATG induction, including significantly improved early graft function with both living and deceased donor kidneys and improved 2- to 12-month function in deceased donor organs ( P = .026). Single-dose lymphocyte counts return to baseline sooner (2.2 vs 15.3 years; P < .05) without increased rejection (1 year; 8.5% single vs 12.5% divided; P = NS), and single-dose induction reduces chronic allograft nephropathy at 1 year ( P = .05). Preliminary results of replacing tacrolimus with MMF show immediately improved renal function (months 1 and 2; P = .02 and .05; months 1–6, P = .058) without increased rejection.

Management of leukopenia in kidney and pancreas transplant recipients

Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post-transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one-yr period of time. By defining leukopenia as a white blood cell count < or =3000 cells/mm(3) and neutropenia as an absolute neutrophil count < or =2000/mm(3), the combined incidence of either leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post-transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti-thymocyte globulin induction, p < 0.05) and/or had rapid steroid withdrawal in the early post-transplant period (44% with vs. 16% without steroid withdrawal, p < 0.05). The most common intervention performed for leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.

Long-Term Results of Rabbit Antithymocyte Globulin and Basiliximab Induction

To the Editor: In our recently reported prospective, randomized, international clinical trial comparing rabbit antithymocyte globulin and basiliximab in renal transplantation (ClinicalTrials.gov number, NCT00235300),1 we observed that induction treatment with rabbit antithymocyte globulin was as safe as and more effective than basiliximab at 1 year in preventing acute rejection in patients who had received kidney transplants from deceased donors and who were at increased risk for acute rejection or delayed graft function. Whether the apparent benefits of rabbit antithymocyte globulin over basiliximab persist is unknown. The duration of follow-up in a clinical study is limited by whether patients are willing . . .

Induction Immunosuppression With Basiliximab in Heart Transplantation

After clinical heart transplantation (HT), it is crucial to use appropriate immunosuppressive agents to prevent rejection. The use of basiliximab or rabbit anti-thymocyte globulin (RATG) for induction therapy has significantly reduced the incidence of acute rejection episodes after kidney transplantation. In this study we sought to examine the effects of basiliximab after HT. From June 2006 to July 2007, we performed 43 HT including patients 18–65 years old undergoing primary HT who were included in this study of basiliximab induction (20 mg intravenous [iv] on days 0 and 4). Cyclosporine and everolimus were given with basiliximab induction. All others received RATG induction (1.5–2.5 mg/kg iv infusion on days 0, 1, and 2) followed by cyclosporine or tacrolimus combined with mycophenolate mofetil. All patients underwent the same operative procedure, steroid-tapering protocol, and postoperative care with protocol endomyocardial biopsy. Basiliximab was well-tolerated and easy to use. There was only 1 operative mortality; the patient died of sepsis due to Enterobacter cloacae. All others survived the operation and are alive and in good health with a 2-year survival rate of 92.86%. No severe adverse events were noted during the first postoperative month. No acute rejection ≥ grade 2R or rejection associated with hemodynamic compromise was noted during the whole course. Basiliximab as induction immunosuppressant was simple, safe, and effective after HT.

Randomized Trial of Single-Dose Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation: An Interim Report

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Rabbit Anti-thymocyte Globulin Induction Therapy Does Not Prolong Survival After Lung Transplantation

Lung transplant survival is limited by the development of bronchiolitis obliterans syndrome (BOS). The strongest risk factor for BOS is acute rejection (AR). We have previously shown that rabbit anti-thymocyte globulin (RATG) induction therapy is associated with a decrease in early AR. Thus, we hypothesized that RATG induction would translate to reduced BOS and improved long-term graft survival. Forty-four lung recipients were prospectively randomized to receive conventional immunosuppression with RATG induction (RATG group) or conventional immunosuppression alone (control group). End-points included graft survival, early and total acute rejection, BOS and treatment complications. There was no difference in graft survival between the groups at 8 years (RATG: 36%; control: 23%; p = 0.48). The RATG group had fewer early rejections compared with the control group (5% vs 41%; p = 0.01). However, the overall rejection incidence did not differ (RATG: 62%; control: 68%; p = 0.52). There was a trend toward a delay in BOS onset among RATG subjects compared with control subjects (2,376 days vs 1,108 days; log rank, p = 0.15). There was no difference in the incidence of infections, but the RATG group had a higher rate of malignancies. Our results suggest that alternative approaches to anti-thymocyte induction should be pursued to reduce BOS and prolong allograft survival.

A randomized trial of alemtuzumab vs. anti‐thymocyte globulin induction in renal and pancreas transplantation

The role of alemtuzumab as an immunosuppressive agent is evolving. We conducted a prospective randomized trial comparing alemtuzumab and rabbit anti-thymocyte globulin (rATG) induction in adult kidney and pancreas transplantation using similar maintenance immunosuppression. Between February 1, 2005 and June 15, 2006 (median follow-up six months), 98 patients were randomized either to alemtuzumab (n = 48) or to rATG (n = 50) induction; 77 (79%) underwent kidney alone (KA) transplant, 17 (17%) pancreas-kidney transplant, and four (4%) pancreas after kidney transplant. Of 77 KA transplants, 66 (86%) were from deceased donors and 31 (40%) from expanded criteria donors (ECD). Re-transplantation, HLA-match, antibody titer, ECD, race, cytomegalovirus status, steroid use, delayed graft function, preservation time, and immunological risk were similar between the two induction groups. Patient, kidney, and pancreas graft survival rates were 100%, 96%, and 95%, respectively. Survival, initial length of stay, delayed graft function, and overall acute rejection rates were similar between alemtuzumab and rATG groups, but acute rejection occurred in nine (20%) rATG patients compared with zero (0%) alemtuzumab patients who received KA transplants (p = 0.007). Mean induction costs differed in the alemtuzumab ($1474) and rATG ($4996, p < 0.001) groups. In the short term after kidney and pancreas transplantation, alemtuzumab and rATG induction therapies are similarly safe and effective.

Early steroid withdrawal in solitary pancreas transplantation results in equivalent graft and patient survival compared with maintenance steroid therapy

Although steroid withdrawal in simultaneous kidney pancreas transplantation has been shown to be feasible, the results of early steroid withdrawal in immunologically solitary pancreas transplantation are not well known. This study evaluated an early steroid withdrawal protocol in this group. The results of steroid withdrawal at 21 d post-transplant in solitary pancreas transplant recipients was compared with a control group consisting of solitary pancreas transplant recipients maintained on steroids (MG). Additional immunosuppression consisted of rabbit anti-thymocyte globulin induction followed by tacrolimus and mycophenolate mofetil in both groups. The withdrawal group (WG, n = 22) consisted of 11 pancreas transplant alone (PTA), six pancreas after kidney (PAK), and five simultaneous cadaveric pancreas living kidney (SPLK) recipients. The steroid maintenance group (MG, n = 32) consisted of 8 PTA, 11 PAK, and 13 SPLK recipients. Recipient and donor demographic characteristics were similar. Seventy eight percent of MG patients had infection-related complications in the first year compared with 50% of the WG patients (p = 0.04). The one-yr rejection, pancreas graft, and patient survival rates were 27.3% 95.5%, and 100% in the WG, and 37.5%, 81.3%, and 93.8% in the MG respectively and not significantly different. We conclude that early corticosteroid withdrawal in isolated pancreas transplantation results in fewer infections and can be achieved without an increased risk of rejection or graft loss over the first year.

Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: Case report and literature review

Thymoglobulin (Genzyme, Cambridge, MA) is an antithymocyte globulin preparation used for induction immunosuppression therapy in solid organ transplantation. It is being utilized with increasing frequency in orthotopic liver transplantation (OLT) in an effort to minimize or delay the use of calcineurin inhibitors due to their inherent nephrotoxicity. Experience with thymoglobulin in OLT remains limited. We report a case of serum sickness in a patient who received thymoglobulin following OLT. The patient experienced intermittent fevers, polyarthralgia, and acute renal failure 9 days after completion of thymoglobulin administration. The patient's symptoms resolved rapidly and completely with a course of intravenous steroids. We review a set of diagnostic criteria for serum sickness and emphasize the importance of early recognition of the process. Early treatment of serum sickness with steroids or plasmapheresis is highly effective and can reduce unnecessary morbidity from this unusual sequela of induction immunosuppression with antithymocyte globulin.

Rabbit Antithymocyte Globulin Induction Therapy in Adult Renal Transplantation

Rabbit antithymocyte globulin (rATG) and horse antithymocyte globulin (horse ATG) are the polyclonal antithymocyte agents available for use in solid organ transplantation in the United States. Horse ATG is indicated for induction immunosuppression and for treatment of acute rejection episodes after kidney transplantation; rATG is indicated for treatment of acute rejection only. However, rATG is commonly used in clinical practice as an induction immunosuppressive agent, instigating many questions regarding appropriate dosing, tolerability, safety, and efficacy. Available evidence supports the use of rATG as an induction agent in adult renal transplant recipients. The use of this product for induction therapy has been studied in conjunction with a full-dose, triple-therapy maintenance regimen (sequential quadruple immunosuppression) consisting of a calcineurin inhibitor, an antimetabolite, and corticosteroids. Rabbit ATG has a proven safety and efficacy profile both as treatment of acute rejection and as induction therapy in patients undergoing kidney transplantation. The most common adverse events associated with rATG are cytokine release syndrome, thrombocytopenia, and lymphopenia. Results of early studies showed an increased rate of cytomegalovirus disease associated with rATG treatment, but recent studies indicate that routine administration of modern antiviral prophylaxis can reduce this risk. Current practice with rATG is evolving to minimize lifelong exposure to calcineurin inhibitors and corticosteroids.