The safety and efficacy of early withdrawal of calcineurin inhibitors in kidney transplant recipients 6 months' posttransplant.
BACKGROUND
The introduction of calcineurin inhibitors (CNIs) in clinical transplantation has resulted in dramatic reduction in acute rejection rate and improvements in short-term allograft survival. However, CNI-induced chronic nephrotoxicity is a clinical concern since it is a major cause of chronic allograft failure. Recent studies suggest that withdrawal or reduction of CNI dosage results in improvement in graft function and survival. The aim of this study was to evaluate the safety and efficacy of substituting CNIs with mycophenolate mofetil (MMF) at 6 months' postkidney transplant.


METHODS
Kidney transplant recipients of first or second grafts (n = 20) maintained on CNI-based therapy and with no history of irreversible acute or vascular rejection were included in the study. Primary end points were the incidence of biopsy-proven acute rejection or treatment failure. Secondary end points included changes in mean serum creatinine and estimated GFR (Cockroft and Gault, CG) over time, incidence of infection, cardiovascular risk factors (blood pressure, cholesterol), graft and patient survival rates, as well as incidence of biopsy-proven chronic allograft nephropathy (CAN). Study patients were compared to a matched control group (n = 20) who remained on CNI-based therapy at equivalent time points.


RESULTS
Incidence of acute rejection following CNI withdrawal was 15%. All episodes reversed with steroid pulses. There was no significant difference in mean serum creatinine or estimated GFR during the follow-up period. No significant change occurred in blood pressure or antihypertensive agents between the groups; however, there was a trend toward lower cholesterol levels after CNI withdrawal. No graft or patient loss was seen during the study period. Biopsy-proven CAN was diagnosed in 2 control patients (10%) at 6 to 8 months' posttransplant.


CONCLUSIONS
Withdrawal of CNI at 6 months following kidney transplantation is associated with an increased risk of rejection and a trend toward lower serum creatinine and cholesterol levels. Further follow-up is needed to establish the long-term results of CNI-sparing regimens on the development of CAN.
Boswell
A
A
Nottingham Kidney Transplant Unit, Nottingham City Hospital NHS Trust, Nottingham, UK.
Evans
L
L
Rigg
K
K
Shehata
M
M
D001794:Blood Pressure; D065095:Calcineurin Inhibitors; D004334:Drug Administration Schedule; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D012086:Reoperation; D016019:Survival Analysis
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid