ImmunosuppressionComparative Analysis of Adverse Events Requiring Suspension of mTOR Inhibitors: Everolimus versus Sirolimus
Section snippets
Materials and Methods
From October 1999 to February 2010, 409 renal transplant patients were converted to an mTORi as primary immunosuppression: 220 to EVL (53.8%) and 189 to SRL (46.2%). Most patients were under a CNI-based immunosuppressive protocol, and all of them had received a renal allograft at least 3 months before conversion to the mTORi. We considered the reasons for all drug eliminations during the follow-up period after the mTORi introduction, comparing their incidences as well as causes.
Results
The initial mean dose was 2.95 ± 0.69 mg/d for EVL and 3.61 ± 1.51 mg/d for SRL. CNI treatment was stopped in all patients after a median of 5 days (IQR, 4–8) in the EVL and 7 days (IQR, 0–14) in the SRL group. The median follow-up was 35 months (IQR, 18–50)
mTORi treatment was prematurely eliminated due to adverse events in 112 patients. In the group treated with EVL the drug was stopped in 69 patients (31.4%); and in the SRL group in 43 patients (22.8%; P = .051). The median time between
Discussion
The first mTORi used in transplantation was SRL, also known as rapamycin (Rapamune; Wyeth Pharmaceuticals, St Davids, PA, USA). The preclinical pharmacologic profile of the new rapamycin analog, EVL, was described in 1997.3 Like SRL, this drug forms a complex with the FK-binding protein complex (FKBP-12), binding with high affinity to mTOR. mTOR is a serine-threonine kinase that is central in a complex intracellular signaling pathway involving cell growth and proliferation, cellular metabolism,
References (11)
- et al.
Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients
Am J Transplant
(2002) - et al.
mToR inhibitors–induced proteinuria: mechanisms, significance, and management
Transplant Rev (Orlando)
(2008) - et al.
Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis
Kidney Int
(2007) - et al.
Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a center
Transplant Proc
(2009) - et al.
Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients
J Lipid Res
(2002)
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