New strategies using 'low-dose' mycophenolate mofetil to reduce acute rejection in patients following kidney transplantation.

Context: Tacrolimus, microemulsion cyclosporine (Neoral), and mycophenolate mofetil (MMF) at 2 and 3 grams daily have demonstrated superior immunosuppressive properties in several recent clinical trials involving solid-organ transplants. An effective immunosuppression may be maintained with lower doses of MMF administered with either tacrolimus or microemulsion cyclosporine.

Objective: To compare tacrolimus plus "low-dose" MMF-based immunosuppressive regimen (TMBIR) with Neoral plus "low-dose" MMF-based immunosuppressive regimens (NMBIR) among kidney transplant recipients.

Design: Prospective, randomized study.

Patients: 53 consecutive adult recipients of kidney transplant. Both groups (TMBIR and NMBIR) were equally matched on demographic characteristics.

Interventions: Participants were randomized to receive orally either tacrolimus (0.08 mg/kg twice daily) (n = 27) or Neoral (4 mg/kg twice daily) (n = 26). Both regimens were started before surgery and continued when allograft demonstrated no postoperative acute tubular necrosis. Both groups received similar "low-dose" MMF (500 mg twice daily) and prednisone (2 mg/kg/day to taper off after 1 year). Switch from tacrolimus to Neoral or vice versa was allowed after refractory rejection or serious adverse events.

Main outcome measure: Acute rejection and patient and graft survival 1 year following kidney transplant.

Results: One-year patient survival rates were 88.9% for the TMBIR group and 100% for the NMBIR group; 1-year graft survival rates were 88.9% for the TMBIR group and 96.1% for the NMBIR group. No significant differences were found in the incidence of biopsy-confirmed acute rejection (14.8% TMBIR vs 23% NMBIR). Steroid-resistant rejections requiring cytolytic antibody therapy were higher in the NMBIR group (50% vs 25%). Three patients crossed over from NMBIR to TMBIR for refractory rejections and 1 patient crossed over from TMBIR to NMBIR for new onset seizure. Three episodes of cytomegalovirus infection were observed in the TMBIR group. Other adverse events were similar in both groups.

Conclusions: Both tacrolimus and microemulsion cyclosporine combined with "low-dose" MMF and corticosteroids provide effective immunosuppression and have similar adverse events in kidney transplant recipients.