Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

Abstract

Chronic allograft nephropathy is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to calcineurin inhibitors. In the present study, effects of a conversion protocol were investigated in pediatric chronic allograft nephropathy with declining glomerular filtration rate (GFR), defined by a Schwartz formula clearance below 60 mL/1.73 m(2)/min, steadily increasing serum creatinine and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kg bodyweight (BW), followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. Calcineurin inhibitors were reduced to 50% at the start of sirolimus and discontinued at median 7 days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m(2)/month, p = 0.025). Individual GFR increased in five out of eight patients (p = 0.026), and only one child exhibited unaltered progression of graft failure. In the responders, mean serum creatinine improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, or on time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, and serum lipids increased transiently. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from calcineurin inhibitors to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy-proven chronic allograft nephropathy.