C2 monitoring in maintenance renal transplant recipients:: Is it worthwhile?

Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C-2) monitoring in maintenance patients. This study evaluates the actual C-2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C-2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1,447 fulfilled the criteria. Valid C-2 and CsA trough concentration (CO) measurements were performed in 1,032 renal transplant recipients (71%) monitored by C-0. Target C-0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C-0 = 112 +/- 31 mug/L, CsA C-2 = 697 +/- 211 mug/L [range 81-1,580 mug/L], CsA dose [mg/day]= 208 +/- 61, CsA dose [mg/kg/day]= 2.8 +/- 1.1, and S-creatinine = 141 +/- 58 mumol/L). A univariate analysis of variance showed that patients with C-2 levels between 700 and 800 mug/L (n = 203, S-creatinine = 136 +/- 49 mumol/L) had significantly lower S-creatinine levels compared with patients with C-2 levels greater than 950 mug/L (n = 94, S-creatinine = 152 +/- 56 mumol/L) (P < 0.02). The same was true for patients with C-2 levels less than 450 mug/L (n = 95, S-creatinine 141 +/- 72 mumol/L) (P < 0.05) when compared with patients with C-2 levels greater than 950 mug/L. There was no significant difference in S-creatinine between patients in the low and intermediate C-2 group; 666 patients had C-0 levels in the therapeutic range (75-125 mumol/L). A linear regression showed a significant relation between S-creatinine and C2 for these patients (P = 0.03). The corresponding relation between S-creatinine and C-0 was nonsignificant (P = 0.3). Monitoring of C-2 in maintenance patients is a valuable tool to detect overexposure to CsA. Until results from prospective studies are available, we recommend C-0 in the therapeutic range and reduction in CsA in overexposed patients, aiming at a C-2 value between 700 and 800 mug/L.