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Corticosteroid Use and Growth After Pediatric Solid Organ Transplantation: A Systematic Review and Meta-Analysis

Tsampalieros, Anne MD; Knoll, Greg A. MD; Molnar, Amber O. MD; Fergusson, Nicholas BSc; Fergusson, Dean A. PhD

doi: 10.1097/TP.0000000000001320
Reviews

Background A number of corticosteroid minimization and avoidance protocols for post–solid organ transplant have been developed. The study objective was to examine the effect of corticosteroid withdrawal/avoidance on growth and safety parameters in pediatric solid organ transplant recipients.

Methods A systematic review using Medline and Embase was performed. All randomized controlled trials (RCT) and observational studies comparing corticosteroid withdrawal/avoidance to controls receiving corticosteroids in pediatric transplant recipients which reported growth as change in height or final height were included. Two reviewers independently abstracted study data and assessed quality.

Results The search yielded 930 records, 14 separate studies involving 1146 patients. Renal RCTs (n = 5) showed that corticosteroid withdrawal/avoidance was associated with a significant increase in growth (mean difference in height standard deviation score [SDS], 0.18; 95% confidence interval [95% CI], 0.07-0.29; P = 0.001) compared with those remaining on steroids. In liver RCTs (n = 2), mean difference in height SDS was −0.20 (95% CI, −1.08 to 0.68; P = 0.66). Results for renal observational studies (n = 5) was 0.34 (95% CI, 0.03-0.65; P = 0.03). The most pronounced effect was seen in prepubertal children with SDS of 0.28 (95% CI, 0.14-0.41; P < 0.0001). In pubertal participants this was not observed (SDS, 0.06; 95% CI, −0.04 to 0.15; P = 0.24). Corticosteroid withdrawal/avoidance was not associated with acute rejection (odds ratio [OR], 0.87; P = 0.63), graft failure (OR, 0.45; P = 0.08), or death (OR, 0.34; P = 0.16) in renal trials.

Conclusions Corticosteroid withdrawal/avoidance in pediatric renal transplantation is associated with a significant improvement in height. Prepubertal patients appeared to have the greatest benefit. Importantly, the improvement in growth was not accompanied by increased rejection or worsening patient/allograft survival in the short term.

Corticosteroid withdrawal/avoidance in pediatric renal transplantation, especially in prepubertal patients is associated with a significant improvement in height without any adverse events, including increased rejection or worsening patient/allograft survival in the short term.

1 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.

2 Division of Nephrology, Children's Hospital of Eastern Ontario, Ottawa, Canada.

3 Division of Nephrology, Kidney Research Centre, Department of Medicine, University of Ottawa, Ottawa, Canada.

4 Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.

Received 17 January 2016. Revision received 14 April 2016.

Accepted 29 April 2016.

A.T. is supported by the Kidney Research Scientist Core Education and National Training Program.

G.A.K. reports grants from Astellas Canada, Novartis Canada and Pfizer Canada outside the submitted work. The other authors declare no conflicts of interest.

A.T. was responsible for the conception and design of the study, analysis and interpretation of data, and drafted and finalized the article. G.K. was responsible for conception and design, analysis and interpreting the data, and drafting and approval of the final article. A.M. was involved with acquisition, analysis and interpretation of data, and drafting and final approval of the article. N.F. responsible for data abstraction and interpretation, drafting and final approval of the article. D.F. was involved in the conception and design of the work, analysis and interpretation of data, and drafting and final approval of the article. All authors approved the final article as submitted and agree to be accountable for all aspects of the work.

Correspondence: Greg Knoll, MD, The Ottawa Hospital, Riverside Campus, 1967 Riverside Drive, Ottawa, Ontario, Canada K1H 7W9. (gknoll@ottawahospital.on.ca).

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