Subclinical inflammation in renal transplant recipients: impact of cyclosporine microemulsion versus tacrolimus

BACKGROUND: Renal insufficiency and renal transplant (RT) provoke a microinflammatory state that leads to increased atherosclerosis. It is not fully known whether calcineurin inhibitors (CNIs) play a role in the inflammation observed in these patients or whether any differences exist between CNIs. OBJECTIVES: The study aimed to establish differences in the inflammatory state of two groups treated with cyclosporine microemulsion (CyA) or tacrolimus (TC). PATIENTS AND METHODS: This prospective study included 81 RT patients divided into two groups according to the CNI: CyA group, n = 35 versus TC group, n = 46. The markers of inflammation (MIF) were determined preRT and at 3 and 12 months' postRT: C-reactive protein (CRP), serum amyloid protein A (SAA), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and pregnancy-associated plasma protein A (PAPP-A). Samples were collected in stable patients in the absence of rejection, active infection, or inflammatory processes. RESULTS: No significant differences existed between the markers of inflammation in the two treatment groups prior to transplantation. At 3 months' posttransplant, patients treated with CyA showed significantly higher levels of IL-6 (P = .05), SAA (P = .03), and sIL-2R (P = .008) compared with patients treated with TC. These differences were maintained for IL-6 (P = .03) and sIL-2R (P = .027) at 12 months' posttransplant. A multivariate analysis at 3 months showed that only age [OR 10.1; CI (95% 2.6-38.4); P = .001], SAA [OR 4.8; IC (95% 1.4-16.5); P = .015], and sIL-2R [OR 4.9; IC (95% 1.5-16.2); P = .009] were independent predictors of the CNI used. At 12 months, age [OR 3.7; IC (95% 0.9-14.2] and sIL-2R [OR 6.04; IC (95% 1.5-23); P = .006] continued to be independent predictors. CONCLUSIONS: Patients treated with CyA displayed significantly higher levels of inflammatory markers (IL-6, SAA, sIL-2R) at 3 and 12 months' posttransplantation, independent of age, gender, time on dialysis, diabetes mellitus (preRT and de novo postRT), and renal function measured by serum creatinine.