title: mTOR inhibitors in pediatric kidney transplantation.
abstract: The mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly being used in pediatric kidney transplantation in different combinations and doses. Several studies have shown beneficial effects of using mTOR inhibitors in children after pediatric renal transplantation. A switch to a low-dose calcineurin inhibitor (CNI) and mTOR inhibitor has been proven to stabilize the glomerular filtration rate. Additionally, de novo studies using a low-dose CNI and an mTOR inhibitor have shown good graft survival and a low number of rejections. Side effects of mTOR inhibitors, such as hyperlipidemia, wound healing problems, and proteinuria, mainly occur if high doses are given and if treatment is not combined with a CNI. Lower doses of mTOR inhibitors do not result in growth impairment or reduced testosterone levels. Treatment with mTOR inhibitors is also associated with a lower number of viral infections, especially cytomegalovirus. Due to their antiproliferative effect, mTOR inhibitors could theoretically reduce the risk of post-transplant lymphoproliferative disease. mTOR inhibitors, especially in combination with low-dose CNIs, can safely be used in children after kidney transplantation as de novo therapy or for conversion from CNI- and mycophenolate mofetil-based regimens.
authors.affiliation: Department of Pediatric Nephrology, Hepatology and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany, larspape@t-online.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Pape
authors.forename: Thurid
authors.initials: T
authors.lastname: Ahlenstiel
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D002648:Child; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D017277:Drug Approval; D000068338:Everolimus; D012739:Gonadal Steroid Hormones / Q000097:blood; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008232:Lymphoproliferative Disorders / Q000517:prevention & control; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D065095:Calcineurin Inhibitors; D012739:Gonadal Steroid Hormones; D007166:Immunosuppressive Agents; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus