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.