A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study

Abstract

BackgroundInduction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy.MethodsImmunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids.ResultsThe per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21–128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22–132) (Thymo-group) (p = 0.69).ConclusionWe found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.

Thymoglobulin vs. ATG-Fresenius as Induction Therapy in Kidney Transplantation: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

“…A lower incidence of acute rejection after the induction treatment of THG is mainly attributed to initial lower lymphocyte counts and later recovery of lymphocyte counts in comparison with ATG-F (47,48). By contrast, the only small-size investigation of THG and ATG-F in kidney transplantation showed similar rates of BPAR and T-cellmediated acute rejection in the 2 year follow-up; peripheral Tcell and B-cell counts at 6 and 12 months were similar and sustained in both groups (16). Our analysis revealed comparable results between THG and ATG-F with regard to acute rejection, although SUCRA values indicated that THG might be more efficacious.…”

“…Second, we conducted a subgroup analysis of studies involving patients of high or low immunological risk to better reflect real-world scenarios. High immunological risk patients refers to those who have higher risk of developing AR and graft loss after transplantation, including patients with PRA > 20%, or re-transplant, or those who are Africa-American (15,16). Third, we conducted the subgroup analysis by excluding the sensitive studies displayed in the funnel plots.…”

“…De novo diabetes is largely attributed to the use of calcineurin inhibitors and steroids (64). These agents are thought to cause beta-cell depletion, and thus, minimizing the use of calcineurin inhibitors and steroids has been proposed (15,16). However, Sánchez-Escuredo et al (65) reported comparable 1 year outcomes of THG, ATG-F, and monoclonal antibody induction in the context of a calcineurin inhibitorfree regimen.…”

Effectiveness and safety of two different antithymocyte globulins used in induction therapy in kidney transplant recipients: A single‐center experience

“…There was also no significant difference in the frequency of nonfatal infectious complications, including CMV infection, between the two ATG formulations, which is consistent with previous observations. 14,15 In contrast, Ducloux et al reported a higher incidence of CMV infections and deaths in the Thymoglobulin group; however, the study used much higher cumulative doses of both agents. 16 Indeed, the benefits of induction therapy with ATGs must be weighed against post-transplant complications, including life-threatening infections.…”

“…Early reports [11][12][13] yielded conflicting results on the frequency of acute rejection episodes and treatment safety issues. The literature after 2000 includes only two small studies (a retrospective analysis with a follow-up period of 3 months 14 and a prospective randomized control study with DSA-positive recipients only 15 ), one retrospective study in 255 kidney transplants from donation after cardiac death, with a short ATG low-dose induction protocol 1 ; and the study by Ducloux et al 16 , which reported a greater incidence of CMV disease, malignancy, and death among patients treated with Thymoglobulin induction. Importantly, this large cohort was treated predominantly with cyclosporine A and azathioprine, and the ATGfixed cumulative doses were relatively high, that is, 21 mg/kg in the ATG-Fresenius and 13 mg/kg in the Thymoglobulin group.…”