New therapeutic strategy improves superior renal function after kidney transplantation

Researchers at Charité - Universitätsmedizin Berlin, together with 16 other transplant centers in Germany and Switzerland successfully tested a new therapeutic strategy that allows for superior renal function after kidney transplantation. The results were published online in the journal "The Lancet".

The study is based on a simple idea: to avoid organ rejection after receiving a kidney transplant, many patients need powerful drugs that suppress the immune system (called immunosuppressive drugs). Indeed, some of these powerful agents protect against the rejection, however, damage the transplanted organ they are intended to protect. Long-term studies have shown that this effect decreases the average survival time after transplantation to eight to twelve years. The scientists led by Prof. Klemens Budde and Prof. Petra Reinke, senior physicians at the Medical Department, Division of Nephrology and the Medical Department, Division of Nephrology and Internal Intensive Medicine, Charité pursued, in the ZEUS-study a novel approach, and replaced the damaging immunosuppressive drugs with non-nephrotoxic drugs.  "The results move the focus in the treatment of kidney transplant recipients to an improvement of renal function as a marker for long-term survival with a functioning graft", sums up Prof. Budde

The investigation focused on the so-called calcineurin inhibitors such as Cyclosporin A. They are part of regular immunosuppressive protocols after kidney transplantion worldwide and only removed if toxic damage is already apparent in the transplanted kidney. The researchers began 4.5 months after transplantation, with a total of 300 patients aged between 18 and 65, to pursue different treatment strategies. One group continued to receive standard therapy with cyclosporine, in a second group cyclosporine was replaced with another drug. Instead, these patients received the drug everolimus, which has no obvious nephrotoxic effects to the graft.

The final examination twelve months after the transplantation, showed significant benefits for this group: The transplant had clearly better renal function compared to patients on standard therapy with cyclosporine, while the rejection rate rose only slightly. Prof. Budde calls this result "very encouraging ", however he cautions: "This is not proof of the superiority of everolimus. We have to wait for the long-term results of this trial."