What is the role of sirolimus (Rapamune) and everolimus (Zortress) in immunosuppression after pediatric transplantation?

Updated: Oct 18, 2019
  • Author: Randy P Prescilla, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Sirolimus (Rapamune) and everolimus (Zortress)

Sirolimus (SRL) and everolimus are structurally related and engage FKBP12 to create complexes that compete for the same intracellular binding protein FKBP12.

Use of SRL has improved graft survival rates and decreased rejection incidence and severity. SRL is more effective when used in combination with CsA. SRL use has also permitted CsA target-level reduction, thereby avoiding or minimizing nephrotoxicity secondary to calcineurin inhibitors. This is because the SRL-FKBP12 complex does not inhibit IL-2 production, unlike the tacrolimus-FKBP12 complex.

Adverse effects include hyperlipidemia (ie, elevated cholesterol, triglycerides), leukopenia, and thrombocytopenia.

One study analyzed linear growth in children who received SRL therapy after renal transplantation versus those who were maintained on tacrolimus, and whether SRL had an adverse effect on growth. Using data from 25 children aged 1-15 years, height z-scores at baseline were compared with those at 24 months. The results noted that height z-scores did not change significantly over 24 months in the SRL group; height z-scores in both groups were no different at baseline and after 24 months. These results suggest that linear growth was similar in groups and SRL did not show an adverse effect on growth. [7]

After a minimum follow-up of 6 months, data from one study noted that sirolimus was effective in rescuing pediatric patients with acute and chronic allograft rejection after liver transplantation; those with calcineurin inhibitor–induced nephropathy realized improved renal function. [8]

Data from another study noted that immunotherapy with the addition of sirolimus improved renal function in pediatric heart transplant patients with calcineurin inhibitor–induced renal insufficiency. Additionally, therapy with sirolimus and lower-dose calcineurin inhibitors can effectively prevent rejection with acceptable adverse effects. [9]

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