1 Division of Renal Transplantation 2 Biochemistry A Laboratory, Necker Hospital, Paris, France
Sir,
Sirolimus (Rapamune®, rapamycin) is a new immunosuppressive agent currently under clinical investigations [1]. Preliminary reports have documented an increase in serum triglycerides (TG) and total cholesterol (TC) levels in renal transplant recipients (RTR) treated by sirolimus combined with cyclosporin A (CsA) and corticosteroids [2,3]. However, there is no report dealing with the effect of sirolimus on lipid levels of RTR not treated by CsA, or with the potential mechanism(s) responsible for such hyperlipidaemia.
Therefore, we studied plasma lipid, lipoprotein, and apolipoprotein (apo) levels, and lipoprotein lipase (LPL) and hepatic lipase (HL) activities in 13 RTR who were transplanted with a cadaveric kidney between June 1996 and June 1997, and who received a treatment with mycophenolate mofetil and corticosteroids combined with either sirolimus (six RTR) or microemulsion CsA (seven RTR). Patient characteristics for age, sex, dose of prednisolone and creatininaemia were similar in both groups. Laboratory tests were performed after an overnight fast and HL and LPL activities were evaluated as described previously [4]. For RTR undergoing hypolipaemic therapy (three patients in the sirolimus group), treatment was stopped at least 1 week prior to the evaluation.
Table 1 indicates plasma lipid, lipoprotein and apo levels as well as HL and LPL activities in the two groups. The results show that although plasma lipid levels, in accord with earlier reports [2,3], and apo levels were higher in the sirolimus group than in the CsA group, there were no significant differences with regard to lipase activities, indicating that the effects of sirolimus on lipid metabolism probably are not mediated by these enzymes. Increased levels of several apo (significant only for apo CII) in the sirolimus group in comparison with the CsA group suggest that an increase in hepatic production of triglyceride- and cholesterol-rich lipoproteins might be involved in the hyperlipidaemia observed in the sirolimus group. Further, more detailed studies of this issue are needed to test this hypothesis.
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