Renal function in children with heart transplantation after switching to CNI-free immunosuppression with everolimus

Pediatr Transplant. 2011 Dec;15(8):784-9. doi: 10.1111/j.1399-3046.2011.01550.x. Epub 2011 Aug 23.

Abstract

Renal impairment because of CNI contributes to long-term morbidity. Therefore, CNI avoiding or sparing treatment strategies are important. In this article, we describe the results of a CNI-free treatment protocol with regard to recovery of renal function. Twenty-eight patients with heart transplantation were switched from CNI regimen to everolimus and mycophenolate, when cGFR was <75 mL/min/1.73 m(2). In all patients, CNI was stopped, when everolimus trough levels of 5-8 ng/L were achieved. Serum creatinine and cGFR were determined before and after 6 and 12 months. Median serum creatinine decreased from 1.2 mg/dL (range 0.7-3.7) before everolimus to 1.0 (range 0.6-1.8) and 1.0 (range 0.5-1.9) mg/dL after 6 and 12 months. Median cGFR was 47.81 (range 18.3-72.6) mL/min/1.73 m(2) before everolimus and 63.1 (range 37.8-108.7) mL/min/1.73 m(2) at six months and 64.8 (range 37.7-106.6) mL/min/1.73 m(2) after 12 months. All changes from baseline to six and 12 months were statistically significant (p < 0.05). Adverse events were infections (n = 3) and rejections (n = 3). Therapy was discontinued in four patients. Conversion to CNI-free immunosuppression resulted in significant improvements of renal function within six months of CNI withdrawal. Side effects are common. However, more studies are required to demonstrate the effectiveness in children.

MeSH terms

  • Adolescent
  • Calcineurin Inhibitors
  • Child
  • Child, Preschool
  • Creatinine / blood
  • Drug Substitution*
  • Everolimus
  • Female
  • Glomerular Filtration Rate / drug effects
  • Graft Survival
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infant
  • Infant, Newborn
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Creatinine
  • TOR Serine-Threonine Kinases
  • Sirolimus