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.
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA. mweir@medicine.umaryland.edu
Matthew R
MR
Weir
Fritz
F
Diekmann
Stuart M
SM
Flechner
Yvon
Y
Lebranchu
Didier A
DA
Mandelbrot
Rainer
R
Oberbauer
Barry D
BD
Kahan
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