Introduction of mycophenolate mofetil and cyclosporin reduction in children with chronic transplant nephropathy

Abstract

Chronic transplant nephropathy (CTN) is the most important cause of kidney graft dysfunction. Studies in adult populations have reported a beneficial effect of non-nephrotoxic mycophenolate mofetil (MMF) on graft function in this setting. However, few studies were reported in children in this setting. We therefore reviewed the charts/medical records of renal transplanted patients < 18 yr of age at a single center who had switched from azathioprine to MMF as a result of progressive loss in graft function, for which vascular, infectious, and urological causes were excluded. Serum creatinine (SCr) and calculated creatinine clearance were compared prior to and after MMF introduction. Thirteen patients (nine male/four female), followed-up for 59.3 +/- 35.4 months after transplantation, were analyzed. Age at MMF introduction was 14.2 +/- 3.6 yr. In 11 patients a previous biopsy had shown features of CTN and four patients also presented signs of chronic cyclosporin A (CsA) nephrotoxicity. MMF was started at a dose of 1211 +/- 351 mg/day, and the CsA dose was decreased from 6.69 +/- 3.15 mg/kg/day 6 months before MMF to 4.8 +/- 2.3 mg/kg/day at the time of MMF introduction. CsA was withdrawn in four patients. The median (25-75%) SCr value increased from 1.60 mg/dL (range 1.3 to 1.87 mg/dL) 6 months before MMF to 2.2 mg/dL (range 1.87-2.32 mg/dL) when MMF was introduced. Six months after introduction of MMF, the SCr level had decreased to 1.5 mg/dL (range 1.2-1.8 mg/dL) and remained stable until the last follow-up (17.5 +/- 9.2 months after MMF was started). A similar pattern occured with calculated SCr clearance. There were no acute rejections after changes in immunosuppression. The safety of MMF was also analyzed and in only one patient was the drug stopped as a result of intractable diarrhea. These findings suggest that MMF is sufficiently powerful to allow a decrease/withdrawal of CsA without the burden of acute rejection in a pediatric population with CTN.

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

“…The main side effect observed with MMF administration was gastrointestinal disturbance, requiring MMF withdrawal in one patient and dose reduction in a further two. This is comparable to findings reported by David-Neto et al [27].…”

“…The findings in our study are supported by the work of David-Neto et al [27], where MMF was substituted for azathioprine together with a concurrent reduction in the CycA dose in 13 paediatric patients, 11 of whom showed evidence of CAN. As in our study, the authors report that the plasma creatinine levels had significantly improved 6 months after the introduction of MMF, this improvement being maintained at a follow up 17.5 months later.…”

Mycophenolate Mofetil in Pediatric Renal Transplantation

“…Over 1 year, seven of 10 in the former group and six of nine in the latter experienced stabilized or improved graft function; of those receiving SRL, 70% developed transient hyperlipidemia and 40% required erythropoietin to treat anemia. Other studies have demonstrated successful CsA reduction or withdrawal following introduction of MMF in pediatric renal transplant patients with CAN (47) or CsA nephrotoxicity (48). In each case, there were marked improvements in graft function following the introduction of MMF (47,48).…”

Cyclosporin A Toxicity of the Renal Allograft – a Late Complication and Potentially Reversible

“…4 mg/kg body weight/day) for long-term immunosuppression is used without a higher prevalence of CsA nephrotoxicity [35, 36]. Therefore we speculate on a specific suspectibility of CsA nephrotoxicity in a given kidney.…”

“…In the pediatric patient population David-Neto et al [35]documented the safety of CsA reduction from a median dose of 6.69 mg/kg body weight/day to 4.8 mg/kg body weight/day (in four patients even withdrawal of CsA) and the addition of mycophenolate-mofetil, with no observed rejection episode. It is of note that in our patients the median CsA dosage (2.0 mg/kg body weight/day) was already in the lower range (133 ng/ml CsA trough level).…”