Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients.
The incidence, pathogenesis, consequences and treatment of mammalian target of rapamycin (mTOR) inhibitor dyslipidemia are not well described. We conducted a systematic review of randomized controlled trials reporting cholesterol and triglycerides in mTOR versus non-mTOR inhibitor immunosuppressive treatment regimens in kidney transplant recipients. All but one of 17 trials reported higher levels of cholesterol and triglycerides, or an increased prevalence of treatment with lipid-lowering agents. Approximately 60% of mTOR inhibitor-treated patients received lipid-lowering agents (2-fold higher than controls). There appeared to be little difference between dyslipidemias caused by sirolimus (14 trials) versus everolimus (3 trials). It was difficult to determine the extent to which declines in lipids over time posttransplant were due to lipid-lowering therapy, changes in doses and/or discontinuations of mTOR inhibitors. From the four trials that measured lipoproteins, it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol. What direct or indirect effects mTOR inhibitors have on atherosclerotic cardiovascular disease in kidney transplant patients are unknown. However, in the absence of the necessary clinical trials, dyslipidemia should be managed, as it would be in nontransplant patients at high risk for cardiovascular disease.
Kasiske
B L
BL
Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA. kasis001@umn.edu
de Mattos
A
A
Flechner
S M
SM
Gallon
L
L
Meier-Kriesche
H-U
HU
Weir
M R
MR
Wilkinson
A
A
D002784:Cholesterol / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015994:Incidence; D016030:Kidney Transplantation; D011494:Protein Kinases / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects* / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases; D014280:Triglycerides / Q000097:blood
D007166:Immunosuppressive Agents; D014280:Triglycerides; D002784:Cholesterol; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus