Background: Chronic calcineurin inhibitor (CNI) toxicity contributes to the development and progression of chronic allograft nephropathy (CAN), which is still the major cause of transplant dysfunction and graft loss. Reduction in dosage of CNI may delay the development of CAN, leading to longer graft survival.
Methods: Therefore, 19 paediatric kidney transplant patients under immunosuppressive therapy with CNI (12/19 ciclosporin A, CSA, 7/19 tacrolimus, Tac), mycophenolat mofetil and some patients on steroids were included in a prospective study. Over a period of 9 months CNI dosage was stepwise reduced from CSA trough levels of 100-150 ng/ml to 50-70 ng/ml and Tac trough levels of 5-8 ng/ml to 2-3 ng/ml, respectively.
Results: Glomerular filtration rate was stabilized in patients after CSA and Tac reduction. One borderline rejection occurred in a patient prior to reduction of Tac. In patients on CSA, one interstitial cellular rejection (BANFF IA) was noted. Reduction of CNI had no significant effects on blood pressure, lipid status and the infection frequency.
Conclusions: In paediatric kidney transplant patients, reduction of CNI down to low trough levels stabilizes renal function. However, the risk of acute rejection episodes may be increased. Therefore, further studies based on protocol biopsies within a randomized trial are warranted.