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 microg/l at 24 hours to the generally accepted 12-hour level of 150 microg/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk factors for nephrotoxicity.

Patients And Methods: Of 212 patients with a stable graft function pre-conversion clinical parameters at 1 and 12 months post-conversion were compared with those at time of conversion. Cyclosporine nephrotoxicity 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 cyclosporine nephrotoxicity were assessed using logistic regression analysis.

Results: The mean cyclosporine trough level rose from 87 microg/l at the time of conversion to 139 microg/l at 12 months post-conversion whereas the daily drug dose increased over the same period from 233 mg to 252 mg. Mean serum creatinine increased by 10% from 135 to 148 micromol/l (p < 0.001). Cyclosporine nephrotoxicity 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 the risk of nephrotoxicity, independent from an effect on blood pressure.

Conclusion: 20% of stable renal transplant patients experienced chronic cyclosporine nephrotoxicity after conversion from a once-daily Sandimmune regimen to a twice-daily Neoral regimen with dose adjustments to a trough level of 150 microg/l. beta-blockers and calcium channel blockers reduced the risk of nephrotoxicity.