Oxford University scientists have shown that a powerful drug given at the time of a kidney transplant operation not only halves the early risk of rejection, but that it also allows a less toxic regimen of anti-rejection drugs to be used after the operation.
The key results are reported in The Lancet and presented at the World Transplant Congress in San Francisco. They will help doctors faced with a difficult transplant conundrum: the powerful combinations of treatments used to prevent early kidney rejection may cause kidney damage later and may subsequently be a cause of transplant failure, the study authors said.
One of the main culprits is a class of drugs known as calcineurin inhibitors. These drugs are very effective at preventing rejection in the first weeks and months after a transplant, but their lasting effects can have serious consequences for the kidney later on.
The 3C study (Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy) tested whether alemtuzumab (Campath; an anti-rejection treatment) partnered with low dose tacrolimus (a calcineurin inhibitor) could reduce transplant rejection when compared with existing treatment.
The study recruited 852 patients who underwent kidney transplantation in the United Kingdom between 2010 and 2013.
"Our primary aim was to find out whether alemtuzumab-based induction therapy would produce worthwhile reductions in acute rejection," said chief investigator professor Peter Friend, from Oxford University's Nuffield Department of Surgical Sciences. "But we also wanted to see whether we could use it with a lower dose of tacrolimus, because there is some evidence that tacrolimus contributes to long-term transplant failure."
Among those allocated alemtuzumab-based induction therapy, 7.3% experienced acute rejection, compared to 16% of those allocated basiliximab-based induction therapy—a halving in the risk of early rejection.
Although alemtuzumab has been available for many years, its use has been limited by concerns about possible side effects, in particular infections.
But no overall excess in serious side effects—such as infections and cancer—was found in patients on the treatment, the scientists report.