Conversion From Azathioprina to Mycophenolate Mofetil in Pediatric Renal Transplant Recipients With Chronic Rejection1

Ferraris, Jorge R.; Tambutti, Mónica L.; Redal, Mar A.; Bustos, Daniel; Ramirez, Jos A.; Prigoshin, Norma

doi:10.1097/00007890-200007270-00010

Cited by 39 publications

(20 citation statements)

References 13 publications

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“…This is in contrast to the findings in the study reported by Anguita et al [25], who studied the effect of converting azathioprine to MMF and found no change in serum creatinine levels after a mean follow up period of 8.6 months. However, Ferraris and colleagues [26] reported that converting azathioprine to MMF in eight paediatric patients with chronic renal rejection led to a significant improvement in creatinine clearance at 15 months. In the latter study the CNI dose remained unchanged.…”

Section: Renal Functionmentioning

confidence: 99%

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

2005

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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.

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Section: Renal Functionmentioning

confidence: 99%

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

2005

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“…The occurrence of chronic transplant nephropathy, associated with calcineurin inhibitor nephrotoxicity, suggests that MMF might be the most important drug on a long-term basis [4,5,6,7]. The occurrence of chronic transplant nephropathy, associated with calcineurin inhibitor nephrotoxicity, suggests that MMF might be the most important drug on a long-term basis [4,5,6,7].…”

Section: Discussionmentioning

confidence: 99%

Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation

et al. 2003

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Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients. We evaluated MPA-PK in 20 stable renal transplant children (11.7±1.9 years) under long-term (46±31 months) MMF (26.1±7 mg/kg per day or 785±183 mg/m 2 per day) therapy plus prednisone and cyclosporin A (n=16), tacrolimus (n=3), or MMF/prednisone (n=1). Total MPA levels were measured using the EMIT-MPA assay at 0, 1, 2, 3, 4, 6, and 8 h after an oral dose of MMF. The level at 12 h was considered equal to the trough level for AUC 0-12 calculation. Mean C 0 , C max , AUC 0-12 , and T max were 3.46±1.32, 13.5±0.58 µg/ml, 63.2±24.4 µg.h/ml, and 1.3±0.6 h, respectively. Six (30%) children were considered to have an adequate exposure (36-54 µg.h/ml) to MPA, 11 (55%) showed an AUC 0-12 >54 µg.h/ml, and 3 (15%) showed an AUC 0-12 <36 µg.h/ml. A C max ≥10 µg/ml was seen in 13 (65%) children. MMF dose did not correlate with AUC 0-12 or C max . The combination of variables C 0 , C 1 , and C 4 provided an equation to predict exposure (r 2 =0.75) where AUC 0-12 =12.62+ (7.78xC 0 )+(0.90xC 1 )+(1.30xC 2 ) (P<0.001). The use of MMF without monitoring MPA blood levels may cause unnecessary overexposure to the drug in stable pediatric recipients.

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“…Only two patients developed rejection episodes (17). Ferraris et al (18) evaluated replacing azathioprine with MMF in 22 pediatric renal transplant recipients. Creatinine clearance increased from 44 to 51 mL/min/1.73 m 2 (p < 0.03) without significant rejection, suggesting that substitution of MMF for azathioprine was effective and improved renal function.…”

Section: Adverse Effects Of Immunosuppressionmentioning

confidence: 99%

Current issues in pediatric transplantation

Kelly

2006

Pediatric Transplantation

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Pediatric solid organ transplantation is so successful that >80% of children will survive to become teenagers and adults. Therefore, it is essential that these children maintain a good quality life, free of significant long-term side effects. While intensive immunosuppressive regimens (containing CsA, tacrolimus, MMF, and steroids) effectively reduce acute or chronic rejection, they can produce long-term side effects including viral infection, renal dysfunction, hypertension, and stunting. The development of effective methods of diagnosis, prevention, and treatment of CMV means that this is no longer a significant cause of mortality, but morbidity remains high. In contrast, infection rates of EBV remain high in EBV-negative pre-transplant patients. However, pre-emptive reduction of immunosuppression or treatment with rituximab or adoptive T-cell therapy is effective in preventing/treating post-transplant lymphoproliferative disease. Recent protocols have concentrated on reducing CsA immunosuppression, to prevent unacceptable cosmetic effects, and to reduce the hypertension, hyperlipidemia, and nephrotoxicity. Both CsA and tacrolimus cause a 30% reduction in renal function, with 4-5% of patients developing severe chronic renal failure. The use of IL-2 inhibitors for induction therapy with low-dose calcineurin inhibitors, in combination with renal-sparing drugs such as MMF or sirolimus for maintenance immunosuppression, should prevent significant renal dysfunction in the future. The concept of steroid-free immunosuppression with IL-2 inhibitors, tacrolimus, and MMF is an attractive option, which may reduce stunting and renal dysfunction. However, these regimens may be associated with the increased development of de-novo autoimmune hepatitis in 2-3% of children. The most important challenge to long-term survival in transplanted children is the management of non-adherence and other adolescent issues, particularly when transferring to adult units, as this is the time when many successful transplant survivors lose their grafts.

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Conversion From Azathioprina to Mycophenolate Mofetil in Pediatric Renal Transplant Recipients With Chronic Rejection1

Abstract: Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.

Cited by 39 publications

References 13 publications

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation

Current issues in pediatric transplantation

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