Risk factors of cyclosporine nephrotoxicity after conversion from Sandimmune to Neoral

Background: In 1995-1996, we switched from a once-daily Sandimmune dose to a twice-daily dose regimen of Neoral. Concurrent with the switch we changed our target trough level from 100 mug/l at 24 hours to the generally accept ed 12-hour level of 150 mug/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk fa ctors for nephrotoxicity. Patients and methods: Of 212 patients with a stab le graft function preconversion clinical parameters at 1 and 12 months post -conversion were compared with those at time of conversion. Cyclosporine ne phrotoxicity was defined as a significant decline of the reciprocal of the serum creatinine concentration over time post-conversion in the absence of other obvious causes for declining graft function. Risk factors of cyclospo rine nephrotoxicity were assessed using logistic regression analysis. Resul ts: The mean cyclosporine trough level rose from 87 mug/l at the time of co nversion to 139 mug/l at 12 months post-conversion whereas the daily drug d ose increased over the same period from 233 mg to 252 mg. Mean serum creati nine increased by 10% from 135 to 148 mu mol/l (p < 0.001). Cyclosporine ne phrotoxicity was present in 42 patients (20%). Cyclosporine dose and trough level did not predict nephrotoxicity but beta -blockers (OR 0.35,95% CI 0. 17-0.72) and calcium channel blockers (OR 0.35, 95% CI 0.19-0.82) reduced t he risk of nephrotoxicity, independent from an effect on blood pressure. Co nclusion: 20% of stable renal transplant patients experienced chronic cyclo sporine nephrotoxicity after conversion from a once-daily Sandimmune regime n to a twice-daily Neoral regimen with dose adjustments to a trough level o f 150 mug/l. beta -blockers and calcium channel blockers reduced the risk o f nephrotoxicity.