Anti-thymocyte globulin induction with delayed introduction of tacrolimus preserves renal function in pediatric liver transplant recipients.
Humans
Child
Adolescent
Tacrolimus
/ therapeutic use
Antilymphocyte Serum
/ therapeutic use
Immunosuppressive Agents
/ therapeutic use
Retrospective Studies
Liver Transplantation
/ adverse effects
Mycophenolic Acid
/ therapeutic use
Kidney
/ physiology
Graft Rejection
/ prevention & control
Graft Survival
anti-thymocyte globulin
antilymphocyte antibodies
complications of liver transplantation
immunosuppression
pediatric liver transplantation
renal insufficiency
tacrolimus toxicity
Journal
Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
15
11
2022
received:
13
07
2022
accepted:
02
03
2023
medline:
17
5
2023
pubmed:
16
3
2023
entrez:
15
3
2023
Statut:
ppublish
Résumé
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. 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. 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. Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post-LT.
Sections du résumé
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.
Substances chimiques
Tacrolimus
WM0HAQ4WNM
Antilymphocyte Serum
0
Immunosuppressive Agents
0
Mycophenolic Acid
HU9DX48N0T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14509Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Informations de copyright
© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.
Références
Miloh T, Barton A, Wheeler J, et al. Immunosuppression in pediatric liver transplant recipients: unique aspects. Liver Transpl. 2017;23:244-256.
de Mattos AM, Olyaei AJ, Bennett WM. Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am J Kidney Dis. 2000;35:333-346.
Lynn M, Abreo K, Zibari G, McDonald J. End-stage renal disease in liver transplants. Clin Transplant. 2001;15(Suppl 6):66-69.
Reding R, Gras J, Sokal E, Otte JB, Davies HF. Steroid-free liver transplantation in children. Lancet. 2003;362:2068-2070.
Mouzaki M, Yap J, Avinashi V, et al. Basiliximab with delayed introduction of calcineurin inhibitors as a renal-sparing protocol following liver transplantation in children with renal impairment. Pediatr Transplant. 2013;17:751-756.
Kivelä JM, Räisänen-Sokolowski A, Pakarinen MP, et al. Long-term renal function in children after liver transplantation. Transplantation. 2011;91:115-120.
Lange NW, Salerno DM, Sammons CM, Jesudian AB, Verna EC, Brown RS Jr. Delayed calcineurin inhibitor introduction and renal outcomes in liver transplant recipients receiving basiliximab induction. Clin Transplant. 2018;32:e13415.
Varo E, López A, Rivero C. Initial immunosuppression in liver transplant recipients with impaired renal function. Transplant Proc. 2005;37:3909-3912.
Tchervenkov JI, Tzimas GN, Cantarovich M, Barkun JS, Metrakos P. The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients. Transplant Proc. 2004;36:1747-1752.
McCauley J, Van Thiel DH, Starzl TE, Puschett JB. Acute and chronic renal failure in liver transplantation. Nephron. 1990;55:121-128.
Newland DM, Royston MJ, McDonald DR, et al. Analysis of rabbit anti-thymocyte globulin vs basiliximab induction in pediatric liver transplant recipients. Pediatr Transplant. 2019;23:e13573.
Schmitt TM, Phillips M, Sawyer RG, et al. Anti-thymocyte globulin for the treatment of acute cellular rejection following liver transplantation. Dig Dis Sci. 2010;55:3224-3234.
Elisofon SA, Magee JC, Ng VL, et al. Society of pediatric liver transplantation: current registry status 2011-2018. Pediatr Transplant. 2020;24:e13605.
Asderakis A, Sabah TK, Watkins WJ, et al. Thymoglobulin Versus Alemtuzumab Versus Basiliximab Kidney Transplantation From Donors After Circulatory Death. Kidney International Reports. 2022.
Lee CH, Gwon JG, Jung CW. Effectiveness of thymoglobulin induction therapy in kidney transplant from deceased donor with mild to moderate acute kidney injury. Transplant Proc. 2019;51:2611-2614.
Dopazo C, Charco R, Caralt M, et al. Low Total dose of anti-human T-lymphocyte globulin (ATG) guarantees a good glomerular filtration rate after liver transplant in recipients with pretransplant renal dysfunction. Can J Gastroenterol Hepatol. 2018;2018:1672621-1672627.
Perito ER, Squires JE, Bray D, et al. A learning health system for pediatric liver transplant: the Starzl network for excellence in pediatric transplantation. J Pediatr Gastroenterol Nutr. 2021;72:417-424.