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Improved long-term graft function in pediatric transplant renal recipients with chronic allograft nephropathy
Larissa Kerecuk1, Catherine Horsfield, Judy Taylor
1Department of Paediatric Nephrology, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK. lkerecuk@doctors.org.uk
Insights
Mycophenolate mofetil (MMF) combined with reduced or stopped calcineurin inhibitors (CNI) improved kidney function and reduced rejection in pediatric renal transplant recipients with chronic allograft nephropathy (CAN). This approach is safe and enhances long-term graft survival.
Area of Science:
- Nephrology
- Immunology
- Pediatric Medicine
Background:
- Chronic allograft nephropathy (CAN) is the primary cause of graft loss in pediatric renal transplant recipients.
- Current management strategies for CAN often involve managing immunosuppression, particularly calcineurin inhibitors (CNIs).
Purpose of the Study:
- To evaluate the efficacy and safety of mycophenolate mofetil (MMF) combined with CNI minimization or withdrawal in pediatric renal transplant recipients diagnosed with CAN.
- To assess the impact of this treatment strategy on graft function, rejection rates, and long-term graft survival.
Main Methods:
- A retrospective single-center analysis of 35 pediatric renal transplant patients with biopsy-confirmed CAN.
- Patients were initiated on MMF, with subsequent CNI minimization or complete withdrawal.
- Graft function (GFR), acute rejection episodes, and adverse events were monitored.
Main Results:
- Following MMF introduction and CNI adjustment, estimated glomerular filtration rate (GFR) improved significantly, reversing prior deterioration.
- The mean GFR improved by 4.0 ml/min/1.73 m(2)/yr after MMF, with a notable initial improvement in the first six months.
- The rate of acute rejection episodes decreased significantly after MMF introduction.
- MMF was discontinued due to adverse effects in only 4 patients.
Conclusions:
- Combining MMF with CNI minimization/withdrawal is a safe and effective strategy for managing pediatric renal transplant recipients with CAN.
- This therapeutic approach leads to initial improvements in GFR, subsequent stabilization, and enhanced long-term graft survival.
Abstract:
CAN is the leading cause of graft loss in pediatric renal transplant recipients. A retrospective single centre analysis of pediatric transplant patients with CAN treated with MMF in conjunction with CNI minimisation/withdrawal is reported. 35 children were successfully started on MMF. The mean age at transplant was 7.9 +/- 0.1 years. MMF was introduced 3.5 +/- 0.1 years after transplantation and patients were followed up for a mean of 32.2 +/- 0.5 months. CAN was confirmed on biopsy in 31 patients. CNI was stopped in 23 patients at a mean time of 16.5 +/- 0.6 months after MMF introduction and minimised in the remaining patients. Prior to MMF introduction, GFR was deteriorating by 21.6 +/- 0.07 ml/min/1.73 m(2)/yr. After MMF, there was an overall improvement in GFR of 4.0 +/- 0.03 ml/min/1.73 m(2)/yr. This was most marked in the first six months when the GFR improved by 20.8 +/- 0.06 ml/min/1.73 m(2)/day. Mean acute rejection episode rate prior to MMF was significantly reduced after MMF introduction. MMF was discontinued in a total of 4 patients due to adverse effects. CNI minimisation/withdrawal with MMF introduction is safe and leads to significant initial improvement with subsequent stabilisation of GFR and improved long term graft survival in pediatric renal transplant recipients with CAN.
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