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Updated: Aug 17, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Replacing calcineurin inhibitors with mTOR inhibitors in children

Rakesh Sindhi1, Joseph Seward, George Mazariegos

  • 1Children's Hospital of Pittsburgh and the University of Pittsburgh, Pittsburgh, PA 15217, USA. rakesh.sindhi@chp.edu

Pediatric Transplantation
|May 25, 2005
PubMed

Insights

Converting pediatric liver and intestine transplant patients from tacrolimus to sirolimus is successful. Early conversion may improve chronic nephrotoxicity and renal function, supporting trials of mTOR inhibitors without calcineurin inhibitors.

Area of Science:

  • Pediatric Solid Organ Transplantation
  • Immunosuppression Therapy
  • Pharmacology

Background:

  • Tacrolimus is a common immunosuppressant in pediatric transplant recipients.
  • Tacrolimus can cause significant side effects, including nephrotoxicity and seizures.
  • Sirolimus, an mTOR inhibitor, offers an alternative immunosuppressive strategy.

Purpose of the Study:

  • To evaluate the success and safety of converting pediatric liver and small intestine recipients from tacrolimus to sirolimus maintenance therapy.
  • To assess the impact of conversion on tacrolimus-related side effects, particularly nephrotoxicity.
  • To explore the potential benefits of sirolimus monotherapy or combination therapy without calcineurin inhibitors.

Main Methods:

  • Retrospective analysis of pediatric patients (n=39) undergoing liver, small intestine, or multivisceral transplantation.
  • Patients were converted from tacrolimus to sirolimus for specific indications (side effects or primary intent).
  • Clinical outcomes, adverse events, and laboratory parameters were monitored post-conversion.

Main Results:

  • Successful conversion to sirolimus was achieved in 78% of patients.
  • Nephrotoxicity was a primary indication for conversion in 14 patients, with significant benefit observed in those converted earlier post-transplant.
  • Adverse events led to re-conversion to tacrolimus in 22% of patients; however, sirolimus was generally well-tolerated with stable hematologic and metabolic parameters.

Conclusions:

  • Conversion from tacrolimus to sirolimus is a viable strategy in selected pediatric liver and intestine recipients.
  • Early conversion may ameliorate chronic nephrotoxicity and improve renal function.
  • Further investigation into mTOR inhibitor-based regimens without calcineurin inhibitors is warranted in pediatric transplantation.

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