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.

Long-term outcome of very early cyclosporine minimization and de novo everolimus therapy in kidney transplant recipients: a pharmacokinetic guided approach.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity is an important cause of chronic allograft dysfunction. Clinical information concerning the impact of very early CsA dose reduction in kidney transplant recipients is limited. We have examined the long-term outcomes of very early CsA dose reduction. This is synchronized with de novo everolimus and steroid therapy. METHODS: We enrolled 10 de novo kidney transplant recipients to receive CsA (target C(0) 250-350 ng/mL) and prednisolone as initial therapy. CsA dosage was reduced by 50% at posttransplant day 7. Everolimus (target trough level, 3-8 ng/mL) was concomitantly started at the day of CsA reduction. Full pharmacokinetic studies of everolimus and CsA were studied at the period of 4-8 weeks after CsA reduction. CsA was then gradually reduced to maintain a trough level of 50-100 ng/mL and/or C(max) <600 ng/mL. RESULTS: The mean follow-up was 51.2 ± 3.45 months. The nadir serum creatinine was 1.03 ± 0.33 mg/dL. The mean initial estimated glomerular filtration rate (eGFR) was 97.97 ± 23.36 mL/min. The mean initial trough everolimus was 5.2 ± 1.5 ng/mL. The eGFR at 1 year, 3 years, and last follow-up was 82 ± 25, 80 ± 21, and 80 ± 25 mL/min, respectively. Patient and graft survival was 100%. CONCLUSION: Very early CsA dose reduction synchronized with de novo everolimus therapy was associated with good long-term patient and graft survival in kidney transplant recipients. This intervention can lead to 75% CsA minimization and is associated with very good GFR by the modification of Diet in Renal Disease Formula at year 4.

Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium.

AIMS: Mycophenolate mofetil is an effective therapy for lupus nephritis (LN) and other glomerulonephritis (GN). However, gastrointestinal (GI) complications can limit its use. Enteric-coated mycophenolate sodium (EC-MPS) has been designed to reduce GI adverse events, but it has not been fully investigated in the treatment of GN. METHODS: Patients with LN and primary GN who had received EC-MPS were studied for effects on renal function. RESULTS: 30 subjects (17 LN, 13 primary GN) were studied. EC-MPS decreased proteinuria in both LN and GN. In LN, 16 patients had EC-MPS as induction therapy. Of these, 8 patients achieved complete remission (CR), 4 had partial remission (PR) and 1 improved renal function. In primary GN, CR was achieved in 4 out of 5 with minimal change disease, but only 1 did not relapse. PR was achieved in 1 of 4 patients with membranous glomerulopathy, 2 out of 2 patients with focal segmental glomerulosclerosis and 1 out of 2 patients with IgA nephropathy. Infections, anemia and alopecia were observed, but no patient had GI side effects. CONCLUSIONS: EC-MPS is effective in LN, but not as effective in primary GN. The risk of GI side effects appears to be low, but other side effects can still occur.