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

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Abstract
Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) 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 C2 and CsA trough concentration (C0) measurements were performed in 1,032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 μmol/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 C0=112±31 μg/L, CsA C2=697±211 μg/L [range 81–1,580 μg/L], CsA dose [mg/day]=208±61, CsA dose [mg/kg/day]=2.8±1.1, and S-creatinine=141±58 μmol/L). A univariate analysis of variance showed that patients with C2 levels between 700 and 800 μg/L (n=203, S-creatinine=136±49 μmol/L) had significantly lower S-creatinine levels compared with patients with C2 levels greater than 950 μg/L (n=94, S-creatinine=152±56 μmol/L) (P 2 levels less than 450 μg/L (n=95, S-creatinine 141±72 μmol/L) (P 2 levels greater than 950 μg/L. There was no significant difference in S-creatinine between patients in the low and intermediate C2 group; 666 patients had C0 levels in the therapeutic range (75–125 μmol/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 C0 was nonsignificant (P =0.3). Monitoring of C2 in maintenance patients is a valuable tool to detect overexposure to CsA. Until results from prospective studies are available, we recommend C0 in the therapeutic range and reduction in CsA in overexposed patients, aiming at a C2 value between 700 and 800 μg/L.