Ten-Year Follow-up of Pharmacokinetics-Guided Very Early Cyclosporine Minimization Synchronized With Everolimus Initiation in De Novo Kidney Transplantation.

BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity.

METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4. The CsA dosage was further reduced to keep a lowest value of serum creatinine and a target EVL level. Primary outcomes were estimated glomerular filtration rate (eGFR) at baseline and last follow-up.

RESULTS: Patients' mean age at last follow-up was 60.6 ± 11.7 years. Follow-up duration was 121.6 ± 12.8 months. Pharmacokinetics study found that Cmax of CsA ranged from 309 to 1,896 ng/mL, mean area under the receiver operating characteristic curve (AUC) of CsA was 3,449 ± 1,402 ng·h/mL, C0 of EVL was 5.2 ± 1.5 ng/mL, Cmax of EVL was 15.4 ± 4.6 ng/mL, and AUC of EVL was 99.7 ± 26.1 ng·h/mL. Achieved nadir serum creatinine was 1.03 ± 0.33 mg/dL. Achieved best eGFR (Modification of Diet in Renal Disease formula) was 99.7 ± 26 mL/min. eGFR at 12 months was 82 ± 25 mL/min. Last serum creatinine was 1.32 ± 0.45 mg/dL. Last eGFR was 57.2 ± 13.55 mL/min. Actuarial death-censored 10-year graft survival was 100%. Actuarial 10-year patient survival was 80%.

CONCLUSIONS: Our intervention can lead to an average of 75% CsA minimization and a very good eGFR at 10 years.