A single-centre, open-label, prospective study of an initially short-term intensified dosing regimen of enteric-coated mycophenolate sodium with reduced cyclosporine A exposure in Chinese live-donor kidney transplant recipients

Abstract

Aims: The nephrotoxicity of cyclosporine A (CsA) accounts for dysfunction of kidney allografts in the clinic. Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) may facilitate CsA sparing after kidney transplantation without compromising safety.

Methods: In a 12-month, single-centre open-label prospective trial, 180 de novo live-donor kidney transplant recipients at low-immunological risk were randomised to a low-dose cyclosporine group which received a low dose of cyclosporine, short-term intensified EC-MPS dosing (2160 mg/day to week 6, 1440 mg/day thereafter) and corticosteroids or a standard-dose cyclosporine group which received a standard dose of cyclosporine, standard EC-MPS dosing (1440 mg/day) and corticosteroids. The primary end-point [treatment failure including biopsy-proven acute rejection (BPAR), graft loss, death], secondary end-point and adverse events were monitored.

Results: The primary end-point (treatment failure) occurred in 13.3% (12/90) of the low-dose cyclosporine group and 16.7% (15/90) of the standard-dose cyclosporine group (p = 0.53) (difference -3.4%, 95% confidence interval -11.7% to 7.5%, based on a noninferiority margin of 20%). BPAR occurred in 11.1% and 13.3% of patients in the low-dose cyclosporine group and standard-dose cyclosporine group, respectively (p = 0.65). The estimated glomerular filtration rate, as calculated by the Cockcroft-Gault formula, was similar at 12 months after transplantation (low-dose cyclosporine group 63 ± 19 ml/min/1.73 m(2) and standard-dose cyclosporine group 59 ± 15 ml/min/1.73 m(2) ; p = 0.43). The levels of serum creatinine and occurrence of adverse events between the two groups were not statistically different.

Conclusions: A regimen of early intensified EC-MPS dosing permits low-dose cyclosporine in live-donor kidney transplant patients at low-immunological risk without compromising efficacy at 12 months' follow-up.