Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference?
BACKGROUND
Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects.


METHODS
To avoid these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid-area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity.


RESULTS
Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28-2.5) per year. In case of relapses, patients had lower predose and estimated AUC0-12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0-12 lower than 44.6 mg·h·L(-1) as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0-12 is >44.6 mg·h·L(-1). During MMF administration, we did not detect any adverse event requiring discontinuation of treatment.


CONCLUSIONS
In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0-12 (>45 mg·h·L(-1)) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.
*Division of Pediatric Nephrology, Department of Pediatric and Adolescent Medicine, University Hospital of Cologne, Germany; †1st Department of Pediatrics; ‡1st Department of Internal Medicine; §Center for Molecular Medicine; ¶Nephrology Research Laboratory, Department II of Internal Medicine; and ║Department of Therapeutic Drug Monitoring, Institute of Pharmacology, University Hospital of Cologne, Germany.
Ágnes
Á
Hackl
Orsolya
O
Cseprekál
Michaela
M
Gessner
Max Christoph
MC
Liebau
Sandra
S
Habbig
Rasmus
R
Ehren
Carsten
C
Müller
Christina
C
Taylan
Jörg
J
Dötsch
Lutz T
LT
Weber
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D019540:Area Under Curve; D002648:Child; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D012372:ROC Curve; D012189:Retrospective Studies
D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid