Mycophenolate mofetil-induced reversal of glomerular filtration loss in children with chronic allograft nephropathy.
BACKGROUND
Mycophenolate mofetil (MMF) has been used for the treatment of chronic allograft nephropathy (CAN) in adults with inconsistent results, but data in children are rare. To evaluate its impact on advanced CAN, we studied changes in glomerular filtration rate (GFR) and the correlation of GFR changes to histology.


METHODS
Thirty-six children (13.1+/-3.6 years) with a progressive decline in GFR of 16.9+/-12.4 mL/min per 1.73 m2/year and biopsy confirmed CAN 4.3+/-2.9 years after transplantation were studied. MMF was added to conventional immunosuppression (IS) consisting of cyclosporine (CsA) and prednisolone (n=26) or tacrolimus (n=1) or replaced azathioprine in triple IS (n=9). Alterations of GFR were correlated to histologic guidelines according to the Banff chronic score (BCS).


RESULTS
One year after conversion, 22 (61%) children showed a rise in GFR (7.5+/-6 mL/min per 1.73 m2), 8 (22%) remained stable, and 6 (17%) showed a further decline of GFR (7.4+/-2 mL/min per 1.73 m2). Mean CsA trough levels were 114 ng/mL before and 98 ng/mL 1 year after conversion. MMF side effects required dose reduction in 14 children. Children responding to MMF with increasing GFR showed a trend toward less fibrosis, less incidence of vasculopathy, and transplant glomerulopathy in the initial biopsy but had a similar incidence of borderline tubulitis compared with the other groups.


CONCLUSIONS
Cotreatment with MMF reversed the progressive loss of GFR in approximately two thirds of children with CAN for at least 1 year. Less chronicity signs in histology seem to indicate a more favorable response to treatment.
Henne
Thomas
T
Children's Hospital, Hannover Medical School, Germany.
Latta
Kay
K
Strehlau
Juergen
J
Pape
Lars
L
Ehrich
Jochen H H
JH
Offner
Gisela
G
D002648:Child; D002908:Chronic Disease; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid