Five-year follow up of thymoglobulin versus ATGAM induction in adult renal transplantation

BACKGROUND: One-year results of a randomized, double-blinded trial of Thymoglobulin versus Atgam for induction therapy in renal transplantation revealed that Thymoglobulin was associated with higher event-free survival (94% vs. 63%), less acute rejection (4% vs. 25%), and better graft survival. This article compares the safety and efficacy of Thymoglobulin versus Atgam induction through 5 years. METHODS: Review and analysis of clinic records and electronic databases. RESULTS: At 5 years, event-free survival (73% vs. 33%, P<0.001), graft survival (77% vs. 55%, P=0.047), and freedom from rejection (92% vs. 66%, P=0.007) were higher with Thymoglobulin versus Atgam. No additional cytomegalovirus (CMV) disease occurred after the first year with Thymoglobulin or Atgam (13% vs. 33%, P=0.056). There were two cases of posttransplant lymphoproliferative disorder (PTLD) with the Atgam arm and none with Thymoglobulin. Thymoglobulin was associated with profound lymphopenia at 2 years after transplantation. CONCLUSIONS: Thymoglobulin was associated with higher event-free survival, graft survival, and freedom from rejection without increased PTLD or CMV disease at 5 years compared with Atgam. The prolonged and profound lymphopenia may contribute to the long-term results associated with Thymoglobulin.     

Sensitization following Thymoglobulin and Atgam rejection therapy as determined with a rapid enzyme-linked immunosorbent assay. US Thymoglobulin Multi-Center Study Group.

Monoclonal and polyclonal anti-thymocyte preparations play an important role in solid organ transplant immunosuppression. While it is generally accepted that blocking anti-idiotypic antibodies can decrease the efficacy of retreatment with mouse monoclonal antibody preparations, sensitization levels and subsequent effects on treatment efficacy are less clear for polyclonal preparations. Serum samples were obtained from 148 patients participating in a multicentre, double-blind randomized phase III trial comparing Atgam (Pharmacia Upjohn, horse anti-thymocyte globulin) with Thymoglobulin (SangStat Medical Corporation, rabbit anti-thymocyte globulin). Recipients of a first or second renal allograft undergoing biopsy proven acute rejection were randomized to treatment with Atgam or Thymoglobulin. Serum samples were analysed for presence of anti-thymoglobulin and anti-Atgam antibodies. Sensitization levels to rabbit IgG in Thymoglobulin-treated patients (68%, n = 54) was similar to sensitization to horse IgG in Atgam-treated patients (78%, n = 54) (two-sided p value = 0.4, Fisher's exact test), although Atgam-treated patients remained sensitized longer (at day 90, 67% anti-horse IgG positive in Atgam treated vs 24% anti-rabbit IgG in Thymoglobulin positive, p = 0.001). No difference was seen in the production of a crossreactive response. Similarly, sensitization had no significant effect on treatment success or failure. For Thymoglobulin-treated patients, the sensitization rate in successfully treated patients was 68%, while inpatients with treatment failures it was 71% (p = not significant, ns). In Atgam-treated patients, the sensitization rate in successfully treated patients was 82%, while in patients with treatment failures it was 67% (p = ns). In conclusion, patients treated with Thymoglobulin and patients treated with Atgam exhibited similar levels of sensitization, presensitization and crossreactive sensitization, although the anti-horse response was longer lasting; neither presensitization nor treatment-induced sensitization appeared to effect treatment efficacy.     

Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report

BACKGROUND: Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients. METHODS: We conducted a historical cohort study to compare rates of survival, rejection, and infection in pediatric (age <19 years) KTx recipients who received induction therapy with polyclonal antibody, ATGAM (n=127) or Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/-15 months for Thymoglobulin recipients. RESULTS: Overall, the incidence of acute rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs. 50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did not significantly differ in patient and graft survival rates, incidence of chronic rejection, EBV lymphoma, or other infection. CONCLUSIONS: Thus, Thymoglobulin induction was associated with a decreased incidence of acute rejection and an increased incidence of EBV infection in pediatric KTx recipients. EBV monitoring should be performed in EBV-naive recipients receiving Thymoglobulin.     

Correlation of histology to clinical rejection reversal: a thymoglobulin multicenter trial report.

Correlation of histology to rejection reversal: A Thymoglobulin Multicenter Trial report BACKGROUND: Histology may provide a link between clinical response to antirejection therapy and graft function. In a subset of centers, renal biopsy was a secondary end point for the Thymoglobulin Multicenter Trial. METHODS: Thirty-eight patients had a protocol biopsy one to two weeks following the end of therapy. Inclusion and post-treatment biopsies were graded and scored according to Banff criteria by a central pathologist who was blinded to the type and outcome of therapy and the timing of the biopsy. RESULTS: The majority of patients (31 of 38) had moderate rejection on their inclusion biopsy. An improvement of at least one Banff grade occurred in 58% of the patients. The treatment was clinically successful in 33 patients, but two thirds of the patients (25 out of 38) demonstrated residual inflammation in the graft. The degree of improvement of inflammation was proportionate to rejection severity (P = 0.006). Banff scoring indicated that residual inflammation was less in Thymoglobulin-treated patients than in those receiving Atgam (P < 0.05) and correlated with the incidence of recurrent rejection (P = 0.015). CONCLUSIONS: These data demonstrate a discrepancy between clinical and histological resolution of acute renal allograft rejection. Residual infiltrates in the graft following rejection therapy are common and, despite clinical improvement, may indicate an increased risk for recurrent rejection.     

A prospective randomized controlled study on the efficacy and tolerance of two antilymphocytic globulins in the prevention of rejection in first-heart transplant recipients

The usefulness of induction phase treatment in heart transplantation is a long-standing debate in the literature. Several centers report good short-term survival without such treatment, but no randomized trial addresses this question. If induction treatment is to be used, most centers prefer rabbit polyclonal antisera to OKT3. However, again, no randomized trial has compared the relative efficacy and tolerance of rabbit antisera. Fifty first-heart transplant recipients with standard triple immunosuppression were randomized to receive ATG Fresenius ( n=24) or Thymoglobulin Mérieux ( n=26) as an induction treatment and were followed for 1 year. The two groups were well matched for gender, age, pre-transplant diagnosis and ischemia time. Actuarial survival at 1 year was 87.5% in the Fresenius group and 84.6% in the Mérieux group (Fisher's exact test; P=1). The average number of rejection episodes per patient was comparable in both treatment groups (Fresenius: mean=2.63, SD=1.44; Mérieux: mean=2.46, SD=2.04). Mean time to first rejection was 48.9+/-37.2 days in the Fresenius group versus 59.6+/-54 days in the Mérieux group (Mann-Witney U-test: z=0.77; P=NS). The total number of rejections across all patients was also comparable (Fresenius: 63; Mérieux: 64) as well as the severity of rejection (seven moderate rejections out of a total of 63 in the Fresenius group and eight out of 64 in the Mérieux group). Eighteen Fresenius (75%) and 15 Mérieux (58%) patients suffered from at least one infection ( P=NS). The tolerance to treatment was excellent in both groups. Total lymphocyte count and all subsets of tested lymphocytes decreased rapidly after the introduction of either antiserum but was more pronounced and persisted for longer in the Mérieux group. ATG Fresenius or Thymoglobulin Mérieux as induction treatments in first-heart transplant recipients treated with standard immunosuppression have the same relative efficacy with regard to survival, acute rejection or infection rate, and are well tolerated.     

Histological Findings of Early Graft Biopsies in Old Donor Renal Transplant Patients Receiving Induction Therapy

Since recipients of transplants from elderly donors are exposed to an increased risk of delayed graft function (DGF) and acute rejection episodes, administration of induction treatment represents an alternative to preserve renal mass and improve graft survival. We compared the evolution and histological findings of early graft biopsies among 38 recipients treated with Thymoglobulim (33.6%) versus 75 (66.4%) with basiliximab. No differences were observes in the rate of DGF (P = .39). Forty kidneys were biopsed during the first 2 weeks after transplantation: 9 in the Thymoglobulin group (23.68%) and 31 in the basiliximab group (41.3%). Histological evaluation showed: acute tabular necrosis in 7 (78%) Thymoglobulin patients versus 14 (45%) basiliximab patients, with calcineurin nephrotoxicity in 2 (22%) and 1 (3.2%), respectively. An acute rejection episode was not diagnosed in the Thymoglobulin group, but 13 patients (17.3%) in the basiliximab group experienced this complication (P = .006). Banff classification showed: 6 grade IA (19.4%), 1 grade IB (3.2%), 3 grade IIA (9.7%), 1 grade IIB (3.2%), and 2 grade III (6.5%). Six of these patients required rescue treatment with Thymoglobulin. Serum creatinine and proteinuria levels between the 2 groups were not different (P > .05). There were no differences in cytomegalovirus (CMV) disease (P = .152), admission due to infection (P = .120), or neoplasia (P = .29). Graft and patient survivals at 3 years did not show a difference. The histological findings revealed that low doses of Thymoglobulin were much more effective to prevent renal inflammation and acute rejection episodes than basiliximab among renal transplant recipients, albiet without differences in survival at a mean of 3 years follow-up.     

Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations.

A group of 79 renal transplant patients undergoing acute rejection episodes were treated with Thymoglobulin (rabbit anti-thymocyte globulin), 1.5 mg/kg/day for 6-14 days as part of a double-blinded trial comparing the efficacy of Thymoglobulin and Atgam (horse anti-thymocyte globulin). Serial serum samples from the patients were tested to determine the level of Thymoglobulin (i.e. rabbit IgG levels = total Thymoglobulin) and anti-Thymoglobulin using ELISAs. Antibodies binding to human lymphocytes (active Thymoglobulin), were determined by flow cytometry; no correlation was seen between treatment efficacy and either active or total Thymoglobulin concentrations; the overall treatment success rate was 86%. Pharmacokinetics of total and active Thymoglobulin were distinctly different; active Thymoglobulin disappeared much more rapidly: only 12% of patients had detectable active Thymoglobulin by day 90 compared to 81% of patients with detectable total Thymoglobulin; percent active Thymoglobulin decreased from a peak of 0.56-0.7% during treatment, to 0.07-0.35% by day 21, and less than 0.14% by day 30. Thymoglobulin and active Thymoglobulin concentrations were modeled by multiple regression. Using dose number and sensitization as independent variables, 47-76% of the variability seen in interpatient Thymoglobulin levels could be explained, while for active Thymoglobulin levels, the measured variables accounted for 13-48% of the observed interpatient variation. We conclude that: (1) for a group of patients receiving primary Thymoglobulin treatment (averaging nine full and one partial dose per patient), neither Thymoglobulin nor active Thymoglobulin levels are predictive of treatment outcome; (2) active Thymoglobulin disappears more rapidly from the circulation than total Thymoglobulin; and (3) patients that develop anti-rabbit IgG antibodies clear Thymoglobulin and active Thymoglobulin more rapidly than unsensitized patients.     

Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation.

The appropriate time point for starting immunosuppressive treatment with calcineurin inhibitors after orthotopic liver transplantation (OLT) has been a subject of debate. The aim of the study was to analyze the effects of anti-thymocyte globulin (ATG) induction therapy on rejection, renal function, infection, tumor rate, and survival. We retrospectively analyzed 391 patients after OLT who had either received calcineurin inhibitors immediately after OLT (n = 129) or after an initial short-term Thymoglobulin induction therapy (n = 262). The 1-year acute rejection rate was 14.5% vs. 31.8% in favor of ATG (P = 0.0008). Rejection grades and the need for treatment also differed significantly (7.3% vs. 23.3%; P = 0.001). Serum creatinine at transplantation was similar in both groups (1.14 mg/dL vs.1.18 mg/dL; P = NS). Postoperative hemofiltration was less frequently seen after induction therapy (P < 0.05). Reduced renal function at 1 year was commonly observed, but serum creatinine (1.26 mg/dL vs. 1.37mg/dL; P = 0.015) and glomerular filtration rate (81 mL/min vs. 75 mL/min; P = 0.02) were far better in the ATG group. Undesired side effects occurred at a similar rate in both groups. Five-year patient survival was also similar in the 2 groups (70.1% and 74.3%; P > 0.05). Short-term ATG induction therapy with delayed administration of calcineurin inhibitors led to a more favorable rejection rate and an improved clinical course in case of a rejection episode. It has beneficial effects on renal function immediately after OLT as well as later, and no additional harmful effects.     

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients

No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1+/-5.2 years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6+/-1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6 months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1 year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1 year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.     

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.     

Long-term immunosuppression, without maintenance prednisone, after kidney transplantation

BACKGROUND: Concern exists that prednisone-free maintenance immunosuppression in kidney transplant recipients will increase acute and/or chronic rejection. METHODS: From October 1, 1999, through February 29, 2004, at our center, 477 kidney transplant recipients (341 living donor, 136 cadaver) discontinued prednisone on postoperative day 6, per our protocol. Immunosuppression consisted of polyclonal antibody (Thymoglobulin) for 5 days, prednisone intraoperatively and for 5 days, a calcineurin inhibitor, and either sirolimus or mycophenolate mofetil. We compared outcome with that of historical controls who did not discontinue prednisone. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 4-year actuarial patient survival (92%), graft survival (90%), acute rejection-free graft survival (86%), and chronic rejection-free graft survival (95%). The mean serum creatinine level (+/- SD) at 1 year was 1.6 +/- 0.6; at 4 years, 1.6 +/- 0.6. We noted that 8% of recipients had cytomegalovirus (CMV) disease; 4.5%, fractures; 2.8%, cataracts; 1%, posttransplant diabetes; 0.2%, avascular necrosis; 0.2%, posttransplant lymphoproliferative disease; and 0%, polyomavirus. In all, 85% of kidney recipients with functioning grafts remain prednisone-free as of April 1, 2004.As compared with historical controls, the recipients on prednisone-free maintenance immunosuppression had better patient (P = 0.02) and graft survival (P < 0.0001) and lower rates of acute (P = 0.0004) and chronic (P = 0.02) rejection. In addition, they had a significantly lower rate of CMV disease (P < 0.0001), cataracts (P < 0.0001), posttransplant diabetes (P < 0.0001), and avascular necrosis (P = 0.0003). CONCLUSIONS: Prednisone-related side effects can be minimized without maintenance immunosuppression; our prednisone-free recipients do not have increased acute or chronic rejection.     

Thymoglobulin induction is safe and effective in live-donor renal transplantation: a single center experience

BACKGROUND: The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. METHODS: Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. RESULTS: Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0+/-1.9 years. The average age of recipients was 44+/-13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P<0.001). CONCLUSIONS: In this analysis, the use of Thymoglobulin in live-donor renal transplantation was associated with an absence of delayed graft function, low acute rejection rates, and high patient and graft survival without increasing the risk of infection or lymphoproliferative disorder.     

Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy

OBJECTIVES: Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment. METHODS: In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine). RESULTS: Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience. CONCLUSION: Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.     

A prospective, randomized, clinical trial of intraoperative versus postoperative Thymoglobulin in adult cadaveric renal transplant recipients

BACKGROUND: Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. METHODS: We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. RESULTS: There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. CONCLUSIONS: The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.     

Long-term toxicity of antithymocyte globulin induction may vary with choice of agent: a single-center retrospective study

BACKGROUND: Antithymocyte globulin (ATG) preparations are frequently used as induction treatment in renal transplantation, but little is known about the clinical equivalence of these different agents. We performed a retrospective, single-center study to compare the long-term clinical effects of ATG Fresenius (ATGF) and Thymoglobulin (SangStat, Fremont, CA) in renal transplant recipients. PATIENTS AND METHODS: A total of 194 consecutive renal transplant recipients were included who had undergone transplantation in our center between June 1993 and April 2001 and had received ATGF or Thymoglobulin as induction treatment. RESULTS: A total of 129 patients received ATGF and 65 patients received Thymoglobulin. Thirty patients (23%) in the ATGF group demonstrated cytomegalovirus (CMV) disease, whereas 24 patients (37%) in the Thymoglobulin group demonstrated CMV (P =0.02). Five patients (3.9%) in the ATGF group and eight patients (12.3%) in the Thymoglobulin group developed posttransplant malignancy (P =0.01). Five patients (3.9%) in the ATGF group and nine patients (13.8%) in the Thymoglobulin group died during follow-up (P =0.005). Cox regression analysis revealed that Thymoglobulin was an independent predictor of CMV disease (relative risk [RR] 2.16, confidence interval [CI] 95% [1.04-4.48]), malignancy (RR 2.16, CI 95% [1.04-4.48]), and death (RR 4.14, CI 95% [1.36-12.6]). CONCLUSION: In renal transplant recipients, induction therapy with Thymoglobulin seems to be associated with a significantly greater incidence of CMV disease, malignancy, and death compared with ATGF.     

Effectiveness of Thymoglobulin Induction Therapy in Kidney Transplant From Deceased Donor With Mild to Moderate Acute Kidney Injury

BackgroundThe clinical benefit of rabbit antithymocyte globulin (Thymoglobulin) compared with basiliximab for induction therapy in kidney transplant (KT) resulting from acute kidney injury (AKI) donors remains controversial. In cases of severe AKI, the degree of kidney injury is too great to reveal influence of different induction therapies on clinical outcomes. We aimed to compare clinical outcomes of Thymoglobulin and basiliximab induction therapy in KTs from deceased donors (DDs) with mild to moderate AKI.MethodsWe retrospectively studied 147 patients who received KTs from DDs between 2009 and 2017 in our center; 91 patients received kidneys from AKI donors. The AKI severity was classified based on the Acute Kidney Injury Network (AKIN) staging, and patients with AKIN stage 3 (43 patients) were excluded. Clinical outcomes were compared according to the type of induction therapy.ResultsThymoglobulin and basiliximab induction groups showed no significant differences in demographic and baseline characteristics except donor age and follow-up period. The Thymoglobulin group had lower incidences of acute rejection and a trend toward a lower incidence of delayed graft function and better graft survival than the basiliximab group. There was no significant difference in BK infection rate; however, cytomegalovirus infection rate showed a trend toward a lower incidence in the basiliximab group.ConclusionsIn cases of KT from AKIN stage 1 and 2 donors, Thymoglobulin showed better clinical outcomes than basiliximab, although it had a somewhat high rate of cytomegalovirus infection. It seems beneficial to use Thymoglobulin induction therapy in KTs from DDs with mild to moderate AKI.     

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.     

Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation

BACKGROUND: There is little published data on the use of antithymocyte globulins in children. This retrospective study describes the use of Thymoglobulin (Imtix, SangStat, Lyon, France) in pediatric cardiac transplantation over a 13-year period in a single center that adjusted the dose of Thymoglobulin according to platelet count monitoring and examines the short-term hematological effects as well as longer-term outcomes. METHODS: Data for all children who received a heart transplant at the H?pital Cardiologique at Lyon from 1984 to 2001 and who were given Thymoglobulin as part of their immunosuppressive protocol were extracted. The dose of Thymoglobulin given depended on baseline platelet count and was 2, 1.5, or 1 mg/kg per day over 5 days for the following platelet count groups: greater than 150,000/mm (normal group), 100 to 150,000/mm (mild thrombocytopenia group), and 50 to 100,000/mm (moderate thrombocytopenia group). RESULTS: Thirty children of median age 14.2 years were given a median cumulative dose of Thymoglobulin of 8 mg/kg per patient; the moderate thrombocytopenia subgroup was given significantly less (6.4 mg/kg) ( P=0.032). Immediate tolerability of Thymoglobulin was good, with no cases of first-dose syndrome, anaphylaxis, or serum sickness. The platelet count decreased at the start of therapy, but recovered after discontinuation, and did not give rise to clinical concern. Patients were followed up for a median of 6.3 years (7 days-15.5 years); actuarial survival was 90%, 86%, and 74.5%, respectively, at 1, 5, and 10 years. In the first year, 50% of patients suffered an episode of rejection. The overall incidence of infection in the month following transplantation was 40%. One lymphoma occurred at 5 months. CONCLUSIONS: The use of Thymoglobulin in pediatric heart-transplant patients as part of an immunosuppressive protocol, with dose adjustment according to platelet levels, has been shown to be effective in terms of rejection rate and patient survival and safe in terms of the incidence of infections and malignancy.     

Induction versus noninduction therapy in kidney transplantation: considering different PRA levels and different induction therapies

To evaluate the rate of acute cellular rejection (ACR) and long-term results in different levels of anti-HLA sensitization, using noninduction or different induction therapies, 763 patients who underwent transplantation from January 1995 to December 2001 were evaluated: 213 patients received induction therapy, 71 received Thymoglobulin (Thymo), 66 Simulect, and 44 OKT3. Follow-up time was at least 1 year for all groups. The Simulect group included older recipients and the OKT3 group had more female patients. Simulect and OKT3 groups had more black patients; Thymo and OKT3 groups had more retransplantations. PRA was low in the noninduction group (mean, 7%) and about the same in the Simulect and Thymo groups (mean, 30%). OKT3 was the most sensitized group (mean = 59%). Dialysis during the first posttransplantation week was more frequent among the induction groups (43% vs 65%; P <.005). Fewer patients experienced rejection episodes in the Thymo group (20% vs 50%; P =.02). Patients were classified according to their level of sensitization, and the Thymo group showed the lower rejection rates in all levels (mean, 20%; P =.001). When analyzing PRA >50%, the Thymo group showed lower rejection rates (12% vs 50%; P =.02). At this level of sensitization, there was no significant difference on graft loss and death with a functioning graft. There was a trend to more cytomegalovirus (CMV) disease in the Thymo group (33% vs 23%; P =.08). Two PTLD were diagnosed, both in the noninduction group. Renal function was better in the Thymo group (1.3 mg/dL). In conclusion, Thymo showed lower ACR rates in all PRA groups. No significant differences in CMV infection, tumors, and patient survival were observed.     

Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients

BACKGROUND: The aim of this study was to investigate the effect of Thymoglobulin and intravenous immunoglobulin (i.v.IG) therapy on the clinical outcome of a putatively high-risk group of kidney transplant recipients who have positive B-cell complement-dependent cytotoxicity (CDC) along with positive T- or B-cell flow cytometry (FC) crossmatch results. METHODS: We prospectively studied the effects of i.v.IG and Thymoglobulin induction treatment in B-cell CDC, and T- or B-cell FC crossmatch-positive kidney transplant recipients (seven women and one man; mean age, 43+/-12 years). RESULTS: Mean peak panel-reactive antibody (PRA) was 47+/-32. Three patients had donor-specific antibody by flow PRA (two anti-DR4 and one anti-A2). Each recipient received induction treatment with i.v.IG 100 mg/kg for 3 days and Thymoglobulin 1.5 mg/kg for 5 days after transplantation. No acute cellular rejections occurred during a median follow-up of 15 months (range, 12-17 months). Only one acute humoral rejection occurred 8 days after transplantation, which responded to plasmapheresis, i.v.IG, and rituximab. One allograft was lost because of polyoma nephritis. Patient survival was 100% and allograft survival was 88%. CONCLUSION: Our results indicate that i.v.IG and Thymoglobulin induction treatment may facilitate kidney transplantation in B-cell CDC and T- or B-cell FC crossmatch-positive patients.