Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Abstract

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3+/-5.8 (range 3.1-82.6) months after transplantation. Patients were followed up for a mean of 13.2+/-2.9 (range 1.2-51.1) months. The mean initial MMF dose was 660+/-56 mg/m2 per day, increased to 1,042+/-73 mg/m2 per day a year later. Cyclosporin was reduced from 138+/-10 mg/m2 per day at MMF introduction, to 116+/-15 mg/m2 per day at 6 months and 107+/-24 mg/m2 per day at 1 year. Six months prior to MMF introduction GFR deteriorated by -32.7+/-7.3 ml/min per 1.73 m2 per year. Six months after the introduction of MMF, GFR improved by +26.2+/-7.1 ml/min per 1.73 m2 per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.

Calcineurin‐inhibitor free immunosuppression with mycophenolate mofetil and corticosteroids in paediatric renal transplantation improves renal allograft function without increasing acute rejection

“…This contrasts with findings from Kerecuk et al. (10) who found a significant reduction in ARE after introduction of MMF. However, in their population, MMF was introduced at a mean of 2.2 yr after transplantation, compared with five yr in this study, and hence fewer ARE would be expected.…”

“…Kerecuk et al. (10) retrospectively studied the change in eGFR of 21 paediatric renal recipients with biopsy proven CAN. CNI was reduced and MMF introduced with a highly significant improvement in mean eGFR.…”

“…As well as for primary immunosuppression, MMF is also used as maintenance therapy in patients diagnosed with CAN, and is associated with an improvement in eGFR, both with the maintenance and withdrawal of CNI in adults (2–4, 6–8, 10), although studies in children have only addressed minimization rather than total withdrawal of CNI (4, 10). Therefore, an important question that remains is whether CNIs can be safely withdrawn in children when MMF is part of the immunosuppressive regimen.…”

Chronic allograft nephropathy

“…The only paediatric CNI-free regimen, the CN-01 study [23] involving induction with sirolimus, anti-CD25 monoclonal antibody and maintenance prednisone, sirolimus and mycophenolate mofetil (MMF), identified no evidence of interstitial fibrosis and tubular atrophy in 12-month protocol biopsies of children who did not experience rejection at 12 months. CNI reduction studies in children maintained on MMF [33, 34] or MMF introduction in children with histological CAN [35–37] showed renal function stabilisation but have not yet reported histological data showing the slowed progression of CAN and further long-term follow-up [33]. However, study protocols that minimise immunosuppression may result in higher rates of SCR and ACR and progression to CAN [19], whereas those that use greater initial immunosuppression run the risk of infectious complications and posttransplant lymphoproliferative disease (PTLD) [23].…”

Improved long‐term graft function in pediatric transplant renal recipients with chronic allograft nephropathy

“…We have previously reported our initial experience of using MMF in 19 paediatric renal transplant patients with CAN along with CNI dose reduction with a mean follow‐up time of 13.2 months (26). Since then, our patient cohort has increased to 35 patients with a much longer mean follow‐up of 32.2 ± 0.5 months.…”