Enhanced clinical utility of De Novo cyclosporine C2 monitoring after lung transplantation

Abstract

Background The 2-hour post-cyclosporine (CyA) dose concentration (C2) is favored as the best single-point correlate of CyA area-under-the-concentration curve. CyA nephrotoxicity is a prominent cause of renal dysfunction that affects 38% of lung transplant (LTx) recipients at 5 years. Methods We assessed the utility of de novo C2 monitoring after LTx by comparing 2 sequential groups of 18 bilateral LTx recipients followed with traditional de novo trough CyA (C0) monitoring and de novo C2 monitoring, respectively. Target C0 levels were 450 μg/liter and 250 μg/liter at 1 week and 3 months (3/12) . Target C2 levels were 1,200 μg/liter and 800 μg/liter. Groups were matched for anthropometrics and diagnoses. Baseline serum creatinine (Cr) was lower in the C0 group than in the C2 group (65 ± 17 vs 81 ± 21 μmol/liter, p = 0.02). Results At 3 months, survival for both groups was 100%, but the C0 group had a greater increase in Cr from baseline (90 ± 54% vs 33 ± 23%, p < 0.001) despite similar CyA dosage (6.6 ± 3.8 vs 6.5 ± 2.9 mg/kg/day, p = 0.94). There was no difference in forced expiratory volume in 1 second (% predicted) (71 ± 16 vs 69 ± 14, p = 0.68), mean acute vascular rejection score per patient (2.61 ± 2.12 vs 1.44 ± 1.72, p = 0.079), mean bronchial rejection score per patient (3.72 ± 1.81 vs 2.83 ± 1.58, p = 0.126) or rate of infection (1.85 vs 1.79 events per 100 patient-days). Conclusions De novo C2 monitoring, which reduces both the risk of CyA toxicity and the risk of sub-therapeutic dosing, is a safe and effective technique for short-term preservation of renal function after LTx.