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-b1;), 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.

In a multicentre trial conducted in eight European centres, 232 recipients of cadaveric renal allografts were randomly allocated to receive either cyclosporin A (CyA, 117 patients) or azathioprine and steroids (control, 115 patients) for immunosuppression. After a follow-up period of up to 11 months, graft survival probability estimates are 73 % in the CyA group and 53 % in the control group. Two deaths have occurred in the CyA group and seven in the control group. 82 % of the CyA group with functioning grafts are receiving CyA alone, 17 % have been changed to azathioprine and steroids, and 1 patient is receiving prednisolone in addition to CyA; 27 % have never received steroids. At 6 months post-transplant, renal function is similar in patients receiving CyA and in those receiving azathioprine and steroids. These preliminary results suggest that CyA is more effective than conventional immunosuppression. CyA therapy avoids the necessity of long-term steroid therapy.