Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)

• Biopsy-proven acute rejection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  Primary outcome for induction therapy comparison
  
  
• Graft function [ Time Frame: 2 and 5 years post-transplantation ] [ Designated as safety issue: No ]
  Primary outcome for maintenance therapy comparison
  
  

• Graft survival [ Time Frame: 6 months, 2 and 5 years ] [ Designated as safety issue: No ]
  
• Serious infection [ Time Frame: 2 and 5 years ] [ Designated as safety issue: Yes ]
  
• Malignancy [ Time Frame: 2 and 5 years ] [ Designated as safety issue: Yes ]
  
• Major vascular event [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
  Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
  
  

The long-term survival of kidney transplants has not improved over the past decade despite reductions in the rate of acute rejection. The commonest cause of late graft loss is chronic allograft nephropathy which is frequently caused by calcineurin inhibitor toxicity. Therefore, it may be possible to improve long-term graft outcomes by reducing the amount of calcineurin inhibitor exposure.

Two possible strategies to do this will be tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) will be compared to standard basiliximab-based induction. All patients will then receive tacrolimus-based maintenance therapy for 6 months (using lower doses in the Campath-1H arm).

At six months, patients will be re-randomised between remaining on tacrolimus and converting to sirolimus (and therefore no longer take calcineurin inhibitors). Patients will then be followed-up in clinic and through routine NHS registries to collect information on relevant outcomes (including graft function, survival, hospitalisations and death).