Total Cholesterol Correlates With Cyclosporine C2 Levels in Kidney Transplant Recipients Under Maintenance Immunosuppression H. Cardinal, A.A. Barama, V. Fradet, M. Lallier, R. Le ´ vesque, G. St Louis, M.J. He ´ bert, C. Girardin, M. Pa ˆ quet, and P. Daloze ABSTRACT The aim of this study was to assess the relationship between cyclosporine (CyA) trough level (C0) and 2-hour postdose (C2) and total cholesterol (TC) in kidney transplant (KT) recipients on Neoral maintenance immunosuppression. In KT recipients who had more than 5 years of follow-up, stable graft function, and stable Neoral dose, we measured C2 and C0 blood levels, serum creatinine, mean total cholesterol (TC) over the last 5 years, prednisone dose, use of beta-blockers and thiazides. Correlations between C0 and C2 levels and TC were performed with the Pearson coefficient. Receiver operating charac- teristics (ROCs) were used to define the threshold with greater accuracy for significant variables at the correlation test. Statistical tests were performed with SPSS 9.5 The C2 correlated with TC (0.31; P = .008) whereas C0 did not. The C2 level was an independent predictor for TC after adjusting for recipient age, gender, dose of prednisone, creatinine clearance, and use of beta-blockers and thiazides (B coefficient = 1.124 E–3 ; P = .009). A threshold C2 value of 700 g/L yielded to a TC level of 5.2 mmol/L. This is the first study to report a correlation between C2 levels and TC. Although C2 explained a small fraction of TC variability, it is an independent predictor of TC in KT recipients on Neoral maintenance immunosuppression. A long-term C2 value under 700 g correlates with better control of hypercholesterolemia. A LTHOUGH the introduction of potent immunosup- pressive agents has dramatically reduced the rate of acute rejection, improving long-term kidney graft survival remains a challenge for the transplant community. Most graft losses occurring 6 months after transplantation are due to patient death or chronic allograft nephropathy (CAN). Cardiovascular disease is still the leading cause of death in these patients. Dyslipidemia is quite prevalent in kidney transplant (KT) recipients 1 and has been associated with cardiovascular events 2 and CAN 3 in this population. Cyclosporine (CyA) is involved in posttransplant dyslip- idemia. 4 There is some conflicting evidence as to whether this is a dose-dependent phenomenon. Whereas some have reported a correlation between through levels of CyA (C0) and lipid abnormalities, 5,6 this has not been found by others. 7 Pharmacokinetic studies have shown that Neoral 2-hour postdose level (C2) is a better monitoring tool than C0 for optimization of CyA immunosuppression. Whether C2 level correlates with cholesterol has not been reported so far. The optimal dose of CyA in maintenance immunosup- pression is unknown. However, targeting CyA levels to minimize risk factors for cardiovascular disease or CAN, such as dyslipidemia, while maintaining adequate levels of immunosuppression, is of clinical interest. METHODS This is a single-center retrospective study. All patients who under- went a KT at the Centre Hospitalier de l’Universite ´ de Montre ´al and had at least 5 years of follow-up in January 2001 were included. All these patients were on Neoral-based immunosuppression and had a stable Neoral dose. All had stable graft function, defined as a variation of serum creatinine (Scr) of less than 20% over the last 3 years. Neoral dose was titrated according to C0 levels, targeting levels of 100 to 200 g/L. Whole blood CyA C0 and C2 were measured once in every patient at their visit in the transplant clinic From the Division of Nephrology (H.C., R.L., G.S.L., M.J.H., C.G., M.P.) CHUM, Ho ˆ pital Notre-Dame, and Department of Surgery (A.A.B., V.F., M.L., P.D.) CHUM, Ho ˆ pital Notre-Dame, Montreal, Canada. Address reprint requests to Azemi Barama, MD, Ho ˆ pital Notre-Dame, 1560 Rue Sherbroke Est, Montreal, Quebec, H2L- 4M1 Canada. E-mail: azemibarama@yahoo.com 0041-1345/04/$–see front matter © 2004 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2004.01.053 360 Park Avenue South, New York, NY 10010-1710 448S Transplantation Proceedings, 36 (Suppl 2S), 448S– 450S (2004)