Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy

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 were tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) was compared to standard basiliximab-based induction. All patients then received tacrolimus-based maintenance therapy for 6-months (using lower doses in the Campath-1H arm).

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

Inclusion criteria

• men or women aged over 18 years
• recipient of kidney transplant (planned in next 24 hours)

Exclusion criteria

• recipients of multi-organ transplant
• previous treatment with Campath-1H
• active infection (including HIV, hepatitis B or C)
• history of anaphylaxis to humanized monoclonal antibody
• history of malignancy (except adequately treated non-melanoma skin cancer)
• loss of kidney transplant within 6 months not due to technical reasons
• medical history that might limit the individual's ability to take trial treatments for the duration of the study