Improved long‐term allograft function in pediatric renal transplantation with mycophenolate mofetil

Abstract

MMF has been shown to decrease the incidence of acute rejection in children and adults at 1 and 3 yr. Other beneficial effects of MMF have been more difficult to demonstrate. Our open‐labeled study presents a 5‐yr data for patients and graft survival, allograft function, and growth in MMF‐treated patients. The trial included 29 patients who were treated with MMF in combination with cyclosporine and methylprednisone. Patients were compared with a preceding group of 29 patients treated with AZA instead of MMF. Patient and graft survival rate 5 yr after transplantation were 97 and 90% in the MMF group vs. 93 and 83% in the AZA group (p: NS). Acute rejection was 20.6% in the MMF group vs. 58.6% in the AZA group (p < 0.01). Chronic rejection was 10.3% in the MMF group and 25% in the AZA group (p: NS). The changes in the creatinine clearance from baseline to 5 yr (Δ) were different between groups (−6.0 ± 5.1 mL/min/1.73 m2 in the MMF group vs. −22.2 ± 7.6 mL/min/1.73 m2 in the AZA group, p < 0.05). Also, the slope of 1/Scr showed a significant lower incidence of worsening renal function after the second year of renal transplantation (p < 0.0001) in the MMF group compared with the AZA group. Δ Height SDS in prepubertal patients was 0.3 ± 0.4 SDS in the MMF group vs. −0.8 ± 0.2 SDS in the AZA group (p < 0.05). This study shows that long‐term MMF therapy has resulted in a decrease in acute rejection and was associated with a protection against renal function deterioration. The use of MMF enables a reduction in the dose of steroids and leads to a linear growth improvement of children after renal transplantation.

Enteric-coated mycophenolate sodium in de novo pediatric renal transplant patients

“…In children, the peak concentration of MPA occurs at approximately 2.5 h after the administration of EC-MPS [15] compared to 1-2 h with MMF [16], which is consistent with findings in adult recipients [10]. In patients receiving cyclosporine (CsA), a single-dose pharmacokinetic study of EC-MPS in children aged [5][6][7][8][9][10][11][12][13][14][15][16] years has demonstrated that 450 mg/m 2 of EC-MPS provides similar MPA exposure (area under the curve, AUC) to 600 mg/m 2 MMF [15,16]. There are no data available, however, on the long-term pharmacokinetics of EC-MPS in children.…”

“…In pediatric renal transplantation, a multicenter trial has demonstrated that drug therapy with the mycophenolate mofetil (MMF) formulation of MPA significantly reduces acute rejection and graft loss relative to that in historical controls receiving azathioprine [4]. While randomized trials in the pediatric population are lacking, other prospective [5,6] and retrospective [7][8][9] studies in children have consistently shown that MMF therapy is effective in preventing acute rejection and associated with good graft survival rates and an acceptable safety profile.…”

Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation

“…This popularity of mycophenolate reflects its proven efficacy in reducing risk for acute renal rejection and its safety and tolerability profile. The incidence of acute rejection is markedly lower, ranging from 15 to 35%, in patients who received MMF compared with those who received either azathioprine or no antimetabolite in combination with a CNI and corticosteroids (85)(86)(87)(88)(89). MMF has also been found to improve 5-year outcome in pediatric renal transplant recipients and prolong half-life of the graft (90).…”

Mycophenolate Mofetil in Pediatric Renal Transplantation

“…Since studies in adult renal transplant recipients had previously established the superiority of MMF over AZA or placebo in reducing the risk of acute rejection, it was important for the pediatric transplant community to have prompt access to open-label studies (12)(13)(14). For a summary of selected published studies of MMF used in combination with CsA and steroids in pediatric renal transplantation, see Table 1 (15)(16)(17)(18)(19)(20)(21)(22).…”