C2 Monitoring – A Continuing Experience
L Boorer, MCT West, WYT Tse, PA Rowe, JA Akoh, H Cramp, J Shaw
Cyclosporin A is a highly lipophilic molecule with wide inter and intra patient variation in absorption. Low oral bioavailability is a risk factor for acute rejection, and excess cyclosporin is associated with an increased risk of chronic allograft nephropathy in renal transplant patients. The area under the concentration-time curve in the first four hours after administration (AUC0-4) is a sensitive marker of cyclosporin absorption and cyclosporin concentration at 2 hours after administration (C2) correlates most closely with AUC0-4). A mean C2 value of 1700ng/mL (range 1300-2000ng/mL) is recommended for the first month.
At our unit, de novo uncomplicated renal transplant patients with favourable matches are given triple therapy of cyclosporin, azathioprine and prednisolone. C2 monitoring was introduced in April 2002. In this cohort no correlation was found between C0 and C2 levels (Chi-square, NS). Of the 25 patients who achieved a C2 level of greater than 1700ng/mL at the end of week one three had rejection (12%). In the remaining 43 patients who had a C2 level of less than 1700 ng/mL at the end of week one fifteen (35%) had histology confirmed rejection (p<0.05, Mann Whitney)
Median (Range) glomerular filtration rate (GFR) as measured by the Cockroft-Gault formula at month 1 was 59.75 (24-95)ml/min for those with a C2 level greater than 1700ng/ml at the end of week 1, compared with 52 (13-110)ml/min for those with a C2 level less than 1700ng/ml at day 7 (p<0.05, Mann Whitney)
Retrospective comparison was also made with 49 patients who received cyclosporin triple therapy over a similar time period, but was measured by cyclosporin (C0). Median (range) GFR in the C2 monitored and C0 monitored groups was 54.2 (13-116) ml/min and 53.63 (10-89) ml/min at 1 month (NS, Mann Whitney) 56.35 (27/106) ml/min and 63 (20-97) ml/min at 3 months (NS, Mann Whitney)
There was no significant difference in the incidence of CMV disease between the C0 and C2 groups.
There was no significant difference in the amount of cyclosporin prescribed for sex and weight matched patients in the C2 and C0 cohorts
In conclusion cyclosporin C2 monitoring in de novo renal transplant patients achieved improved outcomes in this small cohort compared to historical dose adjustments by C0 level, with a trend towards reduced incidence of acute rejection.