Evaluation of a Weight-based Rabbit Anti-thymocyte Globulin Induction Dosing Regimen for Kidney Transplant Recipients.

Although rabbit anti-thymocyte globulin (rATG) is commonly used as induction therapy for kidney transplantation, dosing is not standardized. Recently available findings suggest that even subtle differences in the cumulative dose of rATG induction may have an impact on acute rejection rates for patients receiving steroid-minimization maintenance immunosuppression. This investigation evaluated the potential consequences of rounding and capping rATG doses in patients receiving steroid-containing maintenance immunosuppression when calculating the dose based on actual body weight. Single-center retrospective cohort study. A large academic medical center. A total of 261 adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone. Incidences of biopsy-confirmed acute rejection, opportunistic infections and hematologic effects within 12 months posttransplant were assessed for patients receiving a cumulative rATG dose of 5 mg/kg or higher (5.2 ± 0.2 mg/kg, n=138) compared with those who received a cumulative rATG dose lower than  5 mg/kg (4.5 ± 0.6 mg/kg, n=123). The groups had similar baseline characteristics, immunologic risk, and indications for rATG induction. The incidence of clinically relevant biopsy-confirmed acute rejection was low and similar between the groups (8.7% for rATG of 5 mg/kg or higher vs 8.9% for rATG lower than  5 mg/kg, p=0.944). Patient survival, all-cause graft survival, and graft function did not differ between the groups. Incidences of cytomegalovirus and BK virus infection as well as the extent and duration of lymphopenia were also similar between the groups. In combination with triple maintenance immunosuppression consisting of tacrolimus, mycophenolate, and prednisone, modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection. Measures to optimize rATG utilization present opportunities for cost-saving without sacrificing efficacy in this patient population.

Pennington CA ，Tischer SM ，Lee E ，Lee S ，Sindelar J Jr ，Park JM ... -  《-》

Reduced dose rabbit anti-thymocyte globulin induction for prevention of acute rejection in high-risk kidney transplant recipients.

Klem P ，Cooper JE ，Weiss AS ，Gralla J ，Owen P ，Chan L ，Wiseman AC ... -  《-》

Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation.

Pilch NA ，Taber DJ ，Moussa O ，Thomas B ，Denmark S ，Meadows HB ，McGillicuddy JW ，Srinivas TR ，Baliga PK ，Chavin KD ... -  《-》

Impact of small variations in the delivered dose of rabbit antithymocyte induction therapy in kidney transplantation with early corticosteroid withdrawal.

Tsapepas DS ，Mohan S ，Tanriover B ，Dube G ，Crew RJ ，Cohen DJ ，Hardy MA ，Sandoval PR ，Ratner LE ... -  《-》

Low-dose RATG with or without basiliximab in renal transplantation: a matched-cohort observational study.

In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context. This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4). Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs. In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.

Gentile G ，Somma C ，Gennarini A ，Mastroluca D ，Rota G ，Lacanna F ，Locatelli B ，Remuzzi G ，Ruggenenti P ... -  《-》