Reduction of Calcineurin-lnhibitors in the Long-term Immunosuppression after Paediatric Renal Transplantation – Less Nephrotoxicity, better Graft Function?

The progress in immunosuppression after kidney transplantation in children and adolescents has significantly improved graft survival and reduced acute rejection rate in the first year after transplantation. Nevertheless transplant loss by chronic allograft nephropathy is still an unsolved problem in both, children and adults. One important non-immunologic risk and progression factor of chronic allograft nephropathy is nephrotoxicity of calcineurin-inhibitors. In future the development of non-nephrotoxic immunosuppressive drugs may make ciclosporin A and tracrolimus dispensable. At present, data on adults shows reduction of calcineurin-inhibitors as an option under certain circumstances in children, too. Combination with other potent immunosuppressive drugs as mycophenolate mofetil seems to be mandatory before calcineurin-inhibitors can be reduced. In adults, reduction of calcineurin-inhibitors in the first year after transplantation causes a higher acute rejection rate. In long-term immunosuppression dose reduction of calcineurin-inhibitors shows only a small risk of acute rejection and suboptimal immunosuppression. Graft function, arterial blood pressure, and lipid metabolism improves in adults after calcineurin-inhibitor reduction. Long-term results on graft-survival und patient survival in adults are still missing. The few studies on children do not allow a differentiation between the positive effect of mycophenolate mofetil in chronic allograft nephropathy and the effects of calcineurin inhibitor reduction. Randomised controlled trials with control biopsies are necessary to proof the concept of calcineurin-inhibitor reduction in long-term immunosuppression in children and adolescents.