Anti-thymocyte globulin induction with delayed introduction of tacrolimus preserves renal function in pediatric liver transplant recipients

Pediatr Transplant. 2023 Jun;27(4):e14509. doi: 10.1111/petr.14509. Epub 2023 Mar 15.

Abstract

Background: Tacrolimus (TAC)-mediated renal disease occurs in up to 70% of pediatric liver transplant (LT) recipients. The safety and efficacy of renal-sparing immunosuppression using anti-thymocyte globulin (ATG) induction and delayed TAC administration has not been studied in children. We evaluated the safety and efficacy of ATG induction on preserving renal function in children within the first year (Y1) post-LT in a single-center retrospective cohort study.

Methods: Children under age 18 years of who received isolated LT from 2008 to 2020 with a GFR < 70 received renal-sparing (RS) protocol consisting of ATG with methylprednisolone (MP), delayed TAC administration, lower initial TAC trough goals, and mycophenolate mofetil (MMF). The RS group was matched 1:2 by age and LT indication with standard immunosuppression (SI) group. Changes in renal function as well as adverse events within Y1 post-LT were compared.

Results: Forty-four pediatric patients were included in the analysis, of which 13 received RS. As expected, the RS group had significantly lower mean TAC trough levels at 30 days (10.3 vs. 13.2, p = .001) post-LT. Renal function was significantly preserved at 6 (-0.26 vs. 0.21, p = .004) and 12 months (-0.33 vs. 0.11, p = .003) post-LT in the RS versus SI group as measured by mean change in serum creatinine, with similar trends observed in eGFR and cystatin C. ACR, sepsis, viremia, graft loss and mortality occurred at similar rates in both RS and SI groups.

Conclusion: Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post-LT.

Keywords: anti-thymocyte globulin; antilymphocyte antibodies; complications of liver transplantation; immunosuppression; pediatric liver transplantation; renal insufficiency; tacrolimus toxicity.

MeSH terms

  • Adolescent
  • Antilymphocyte Serum / therapeutic use
  • Child
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney / physiology
  • Liver Transplantation* / adverse effects
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies
  • Tacrolimus* / therapeutic use

Substances

  • Tacrolimus
  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Mycophenolic Acid