Clinical trial of daclizumab in living renal transplantation

Choi, Yoon Seok; Park, Chang Sue; Park, Mi Jung; Kim, Ji Hwan; Jeon, Jee Min; Kim, Sung Min; Park, Yong Ki; Lee, Jong Myeong; Shin, Yong Hun; Kim, Joong Kyeong

Abstract

BACKGROUN: Despite improvements in immunosuppressive therapy for use in renal transplantation, acute graft rejection remains a risk factor of chronic rejection and a major cause of graft loss and patient death. Recently, daclizumab, an anti IL-2 receptor monoclonal antibody has been shown to reduce the incidence of acute rejection.
METHODS
To investigate the immunosuppressive effect of daclizumab and the incidence of acute rejection, we administered daclizumab intravenously (1 mg/kg of body weight within 24 hours before transplantation and once every other week afterward, for a total of 5 doses) in combination with cyclosporine microemulsion (CsA), steroid and mycophenolate mofetil (MMF) to 68 transplant recipients
RESULTS
Among them 62 were undergoing their first transplantation and 6 were undergoing their second transplantation. 32 patients received living-related transplants and 36 patients received living-unrelated transplants: their HLA match were as follows:1 case with 1 Ag match, 13 cases with 2 Ag matches, 18 cases with 3 Ag matches, 3 cases with 4 Ag matches, 1 case with 5 Ag matches. The clinical characteristics of patients treated with daclizumab were as follows: 42 were male, 26 were female; the mean age of recipients was 42.94 +/- 11.2 years and that of donor was 34.1 +/- 9.9 years. The underlying renal diseases were glomerulonephritis (n=47), reflux nephropathy (n=6), diabetic nephropathy (n=12), polycystic kidney disease (n=2) and acute renal failure (n=1). During the observed period (17.41 +/- 4.34 months; min. 6 months, max. 26 months), 2 cases had acute rejection in the third month after transplantation and 1 case in the 6th month after transplantation, 1 case in the 24th month after transplantation (4/68, 5.8%). In the historical control, 20.8% of acute rejection (10/48) were noted in CsA, MMF and steroid regimen group and 36% of acute rejection (22/60) in CsA, azathioprine and steroid group. Serum creatinine level was 1.21 +/- 0.23, 1.31 +/- 0.25, 1.35 +/- 0.28 and 1.34 +/- 0.31 (mg/dL) during the 1st, 3rd, 6th month and 1 year after transplantation respectively. 10 patients developed herpes-zoster infection and 6 patients had CMV infection. 1 patient expired due to CMV pneumonitis on the 3 months after transplantation. The 2-year graft survival rate was 98.5% with daclizumab and 45 months graft survival rates were 92.9% and 89.3% for MMF group and azathioprine group respectively.
CONCLUSION
Daclizumab, used in combination with CsA, MMF and steroid, reduced acute rejection episodes without serious short term side effects. Further observation is needed to evaluate the graft survival rate and uncover any long-term side effects.