Low-dose mycophenolate mofetil is an effective and safe treatment to permit phased reduction in calcineurin inhibitors in chronic allograft nephropathy

Transplantation. 2005 Feb 15;79(3):304-9. doi: 10.1097/01.tp.0000151145.12706.2a.

Abstract

Background: Chronic allograft nephropathy (CAN) is the most common cause of long-term renal-allograft dysfunction and the second most common cause of transplant loss. There are concerns that prolonged patient exposure to calcineurin inhibitors (CNIs) exacerbates or promotes the process of CAN.

Methods: In our unit, we carried out an observational study over the period 2000 to 2003 using low-dose mycophenolate mofetil (MMF) to facilitate a phased reduction in the dose of CNI in a group of patients with CAN. Low doses of MMF were chosen to minimize adverse effects and to reduce levels of CNIs without the attendant risks of under-immunosuppression.

Results: A step-wise reduction in mean reciprocalised creatinine was evident over the run-in period (mean 1/creatinine before MMF=0.005739-0.000083*month; R=0.77) with a step-wise monthly improvement postintroduction of MMF and dose reduction of CNI (mean 1/creatinine after MMF=0.004609+0.000049*month; R=0.74) (P<0.0001). The mean Cockroft-Gault estimated creatinine clearances were 47.1+/-24.2, 37.2+/-16.3, and 41.6+/-21.1 mL/min at time [t]=-12, t=0 and t=+12 months, respectively. Low-dose MMF therapy was well tolerated (only 7/89 patients stopped MMF because of side-effects in the first 12 months), and acute rejection was noted in only one patient. At latest follow-up, only 17 transplant losses had occurred, of which 6 patients had died with a functioning graft.

Conclusions: Low-dose MMF was well tolerated and resulted in prolonged graft survival.

Publication types

  • Clinical Trial

MeSH terms

  • Biopsy
  • Calcineurin Inhibitors*
  • Creatinine / blood
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / mortality
  • Kidney Transplantation / pathology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use*
  • Prednisolone / therapeutic use
  • Survival Analysis
  • Survivors
  • Time Factors
  • Transplantation, Homologous

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Prednisolone
  • Creatinine
  • Mycophenolic Acid