Reassessing Rabbit Antithymocyte Globulin Induction in Kidney Transplantation (RETHINK): An Analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry

Abstract

Background. There is no consensus on rabbit antithymocyte globulin (rATG) dose used for induction immunosuppression in pediatric kidney transplants. We aimed to identify whether a lower rATG dose provides safe and effective immunosuppression compared with a higher dose. Methods. We retrospectively analyzed all first-time kidney transplant recipients (aged <21 y) in the North American Pediatric Renal Trials and Collaborative Studies registry since 1998 on mycophenolate mofetil– and tacrolimus-based immunosuppression with rATG induction. An a priori cutoff of 7.5 mg/kg cumulative rATG dose was used to identify low (<7.5 mg/kg) and high (≥7.5 mg/kg) exposure groups. Primary outcome was time to first-acute rejection episode. Secondary outcomes included graft function, patient survival, hospitalizations due to infections, and time to first-posttransplant lymphoproliferative disorder episode. Results. Four hundred fifty-five patients met inclusion criteria (59% male, 49% whites, 26% blacks, 38% living donor source). Median cumulative rATG dose was 6.8 mg/kg with a median of 5 doses and a median 1.5 mg/kg/dose introduced at a median of postoperative 0 days. Sixty-four percent received <7.5 mg/kg total rATG. There was no difference in age at transplant, gender, race, end-stage renal disease causes, or HLA mismatch among groups. Time to first-acute rejection was similar (P = 0.07). There was no significant difference in graft or patient survival or time to posttransplant lymphoproliferative disorder. Hospitalization for infection rates was similar. Conclusions. These data demonstrate a wide variation in cumulative rATG induction dose. A smaller rATG dose <7.5 mg/kg may provide effective and safe immunosuppression compared with a higher dose.

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium

“… 7 , 11 , 12 , 13 We have previously demonstrated a down trend in median cumulative rATG induction dose from 7.9 mg/kg (1998–2008) to 6.3 mg/kg (2009–2016) in the North American Pediatric Renal Trials and Collaborative Studies registry. 14 In that analysis, we did not identify a difference in patient and graft outcomes using a threshold of 5 rATG induction doses (7.5 mg/kg). Although data from Tsapepas et al.…”

Induction and maintenance immunosuppression in pediatric kidney transplantation—Advances and controversies

“…A recent study using (NAPRTCS) registry data showed that 60% of pediatric kidney recipients in the US received ATG cumulative dose of <7.5 mg/kg. The study found no difference in time to acute rejection between recipients of <7.5 mg/kg dose and ≥7.5 mg/kg dose 38 . Special considerations for ATG dosing are given in Table 1 39 …”

“…The study found no difference in time to acute rejection between recipients of <7.5 mg/kg dose and ≥7.5 mg/kg dose. 38 Special considerations for ATG dosing are given in Table 1. 39 Acute reactions during ATG administration are related to cytokine release syndrome.…”

Efficacy and safety of single‐dose anti‐thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study

“…[12][13][14] However, recent studies have demonstrated that lower doses of r-ATG may be safer without loss of efficacy, including the use of a single dose. [15][16][17][18] Recently, a natural experiment conducted in our center demonstrated that, in adult kidney transplant recipients, the use of a single 3 mg/Kg r-ATG dose was associated with an 81% lower risk of acute rejection, without an increase in the risk of CMV infection compared to no induction. 19 Typically, pediatric kidney transplant recipients receive induction therapy with anti-IL-2R monoclonal antibodies.…”

“…The use of r‐ATG has consistently shown higher efficacy for the prevention of acute rejection compared to anti‐IL‐2R monoclonal antibodies, 8–11 but concerns still exist regarding the increased risk of infections and cancer, especially at the initial doses of 1–1.5 mg/kg over 7–10 days 12–14 . However, recent studies have demonstrated that lower doses of r‐ATG may be safer without loss of efficacy, including the use of a single dose 15–18 …”