COMPLICATIONS - CARDIOVASCULAR

M. Kouwenberg, D. Gommers, L. Hilbrands
Nephrology, Radboud University Nijmegen Medical Center, Nijmegen/NETHERLANDS

Body: Introduction. Because of the high incidence of cardiovascular diseases after renal transplantation, it is important to consider the effects of immunosuppressive drugs on blood pressure (RR) and lipid metabolism. It is well known that tacrolimus (Tac) is less unfavorable than cyclosporine in this respect. However, whether Tac itself has any effect on these parameters is not clear. Small studies in healthy volunteers and patients with auto-immune diseases suggest no major impact, but data in (renal) transplant patients are not available. In a prospective study on immunosuppressive drug minimization, we discontinued Tac from 6 months after renal transplantation, and examined the resulting changes in RR and serum lipids. Methods. Patients eligible for this study used Tac in combination with prednisone and either azathioprine or mycophenolate mofetil. The Tac dose was tapered to zero during a period of 4 weeks while the prednisone dose was increased from 0.10 to 0.15 mg/kg/d. RR was measured immediately before Tac withdrawal and 4 weeks after complete withdrawal. Serum lipid levels were measured within a period of 3 months preceding withdrawal and again between 2 and 4 months after complete cessation of Tac. Patients with an acute rejection after Tac withdrawal were excluded. Results. We analysed the data of 53 patients who started with Tac withdrawal at a median time of 204 days (interquartile range 188-237 days) after transplantation. At that time the Tac dose was 0.08±0.05 mg/kg/d, the Tac level was 7.0±1.9 µmol/l, and the prednisone dose was 8.7±1.7 mg/d. Four weeks after cessation of Tac, the prednisone dose was 11.0±1.9 mg/d. We observed no changes in systolic RR (135.6±17.5 before vs. 135.3±19.0 mm Hg after Tac withdrawal), diastolic RR (82.1±7.7 vs. 83.0±8.1 mm Hg), and number of antihypertensive drugs (1.6±0.9 vs 1.6±0.8). There were also no changes in total cholesterol (5.05±0.97 vs. 4.99±0.95 mmol/l), LDL cholesterol (3.04±0.78 vs. 3.05±0.77 mmol/l), and HDL cholesterol (1.19±0.36 vs. 1.33±0.36 mmol/l), but the concentration of triglycerides decreased from 2.0±1.3 to 1.5±0.7 mmol/l (P<0.01), while the number of patients using statins slightly increased from 16 to 23%. Conclusion. In renal transplant patients who use a maintenance dose of tacrolimus, discontinuation of the drug does not lead to changes in RR and cholesterol levels. Combined with data in other populations, this indicates that tacrolimus has no relevant effect on blood pressure and lipid metabolism.

Disclosure: All authors have declared no conflicts of interest.