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Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy
Jutta C Falger1, Thomas Mueller, Klaus Arbeiter
1Kinderdialyse, Department of Pediatrics, AKH Wien, Medical University of Vienna, Vienna, Austria.
Abstract:
CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr 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/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. 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 CNIs 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 CAN.
Insights
Converting pediatric renal transplant patients with chronic allograft nephropathy (CAN) from calcineurin inhibitors (CNIs) to sirolimus stabilized graft function. Most children showed improved GFR and stable serum creatinine, with manageable side effects.
Area of Science:
- Nephrology
- Pediatric Transplantation
- Immunosuppression
Background:
- Chronic allograft nephropathy (CAN) is a primary cause of renal allograft loss.
- Calcineurin inhibitors (CNIs) are nephrotoxic, necessitating alternative immunosuppressants.
- Sirolimus offers a non-nephrotoxic option for managing CAN.
Purpose of the Study:
- To evaluate the efficacy of converting pediatric patients with biopsy-proven CAN and declining GFR to sirolimus.
- To assess the impact of sirolimus conversion on renal function and allograft stability.
- To determine the safety and tolerability of sirolimus in this patient population.
Main Methods:
- Eight pediatric patients with CAN and GFR < 60 mL/1.73 m²/min were switched from CNIs to sirolimus.
- Sirolimus was initiated with a loading dose followed by a daily dose to achieve trough levels of 15-20 ng/mL.
- CNIs were tapered and discontinued within seven days of sirolimus initiation.
Main Results:
- Glomerular filtration rate (GFR) changes stabilized significantly post-conversion (-2.9 vs. +0.4 mL/min/1.73 m²/month).
- Five of eight patients experienced improved GFR, and mean serum creatinine improved by 0.3 mg/dL in responders.
- Infectious complications occurred in about half the children; however, no graft loss was observed during the study period.
Conclusions:
- Conversion from CNIs to sirolimus effectively stabilizes renal graft function in most children with biopsy-proven CAN.
- Sirolimus offers a tolerable immunosuppressive strategy with a favorable safety profile for managing chronic allograft nephropathy.
- This conversion protocol demonstrates potential for improving long-term allograft survival in pediatric renal transplant recipients.
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