mTOR inhibition: the learning curve in kidney transplantation.
All immunosuppressive medications require a learning curve that enables clinicians to improve the therapeutic index of agents. Mammalian target of rapamycin (mTOR) inhibitors are potentially a less nephrotoxic form of immunosuppression than calcineurin inhibitors (CNIs) that has been used in kidney transplant recipients for more than two decades. This drug class has a novel immunosuppressive action, probably mediated in part through inhibition of growth receptor signaling mechanisms. In addition, it has a unique drug toxicity, which is partially dose-related. This medication class also possesses antiproliferative activity, which may be useful in-post-transplant patients with increased atherosclerotic and malignancy risks. mTOR inhibitors have been utilized for de novo immunosuppression with CNIs, corticosteroids, and antimetabolites. mTOR inhibitors also have been used as CNI-sparing agents both early and late post-transplant. Much debate remains over how to best utilize mTOR inhibition in kidney transplantation.
Weir
Matthew R
MR
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA. mweir@medicine.umaryland.edu
Diekmann
Fritz
F
Flechner
Stuart M
SM
Lebranchu
Yvon
Y
Mandelbrot
Didier A
DA
Oberbauer
Rainer
R
Kahan
Barry D
BD
D000818:Animals; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000150:complications / Q000209:etiology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods*; D051379:Mice; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases