Cyclosporine dose reduction in stable renal transplant patients with high C2 level: simplified method of single C2 measurement and individualization of C0 target

Summary It is recommended that cyclosporine dosing should be based on the whole blood level 2 h after a dose (C2), not the trough level (C0). Initial studies did not however establish the outcome of dosing according to C2 levels in long‐term patients previously managed by C0 levels. C0 and C2 were measured in 152 stable patients receiving Neoral therapy, mean 86.9 months after transplantation. This showed that 38 (25%) had C2 levels above a target range of 700–900  μ g/l. Higher C2 levels were associated with higher cholesterol levels ( P  = 0.0058) and higher diastolic blood pressure ( P  = 0.0163). Cyclosporine dose reduction was undertaken in 32 patients with high C2 levels. For logistical reasons, C2 was not performed regularly, but an individualized C0 level was set for each patient. A 16% reduction in mean cyclosporine dose was achieved, associated with a 28% fall in mean C0, from 212 to 153  μ g/l, and a 25% fall in mean C2, from 1075 to 820  μ g/l. There was no excess in adverse events in the dose reduction cohort, compared with patients with initial C2 levels <900  μ g/l. Over a mean 15 month follow‐up period in the dose reduction cohort, there was a 4.4% reduction in mean diastolic blood pressure, from 84.9 (SEM 2.1) to 80.2 (1.9) mmHg, P  = 0.023; and a 10.4% reduction in mean cholesterol, from 5.71 (0.27) to 5.11 (0.25), P  = 0.005 (patients starting on statin during follow‐up excluded). In patients with initial C2 <900  μ g/l, blood pressure did not fall and the cholesterol fell by 3.9%, from 5.27 (0.14) to 5.07 (0.15) mmol/l ( P  = 0.0405). In conclusion, cyclosporine dose reduction was safe in stable long‐term renal allograft recipients with high C2 levels. There was an improvement cholesterol levels and a small improvement in blood pressure after cyclosporine dose reduction.