Mycophenolate mofetil following glucocorticoid treatment in Henoch-Schönlein purpura nephritis: the role of early initiation and therapeutic drug monitoring

Pediatr Nephrol. 2018 Apr;33(4):619-629. doi: 10.1007/s00467-017-3846-6. Epub 2017 Nov 25.

Abstract

Background: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood and traditionally considered as a self-limiting disease. However, renal involvement can unfavorably determine long-term prognosis. The reported regimens to treat HSP nephritis (HSPN) are diverse, indicating that the most effective treatment remains controversial.

Methods: This retrospective, single-center study involved 18 patients presenting with HSPN and nephrotic-range proteinuria. We aimed to investigate the efficacy and safety of mycophenolate mofetil (MMF) and identify a cut-off level for estimated mycophenolic acid area under the curve (eMPA-AUC0-12h) values, which can predict complete remission with high sensitivity.

Results: Despite prior insufficient therapeutic response to corticosteroids, 89% of patients showed a significant decrease in proteinuria after 1 month of MMF treatment. None of them relapsed during treatment; however, two children relapsed after discontinuation. Based on results of a receiver operating characteristic (ROC) analysis, an eMPA-AUC0-12h >56.4 mg*h/l was a predictor for complete remission within 3 months (80% sensitivity, 83.3% specificity, p = 0.035). During MMF administration, we encountered no adverse event requiring discontinuation of treatment.

Conclusion: Our study demonstrates that MMF is a safe and potentially effective secondary treatment option for children with HSPN to achieve and maintain long-term remission without serious side effects. To achieve complete remission within 3 months, resolve severe inflammatory glomerular lesions, and avoid progression to chronic kidney disease, we propose timely diagnosis and early initiation of MMF with an eMPA-AUC0-12h value of 56.4 mg*h/l.

Keywords: Cut-off of eMPA-AUC0-12h; Mechanism of action; Mycophenolic acid; Pre-dose level; Therapeutic drug monitoring.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Drug Monitoring / methods*
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Germany
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • IgA Vasculitis / complications
  • IgA Vasculitis / drug therapy*
  • Kidney / pathology
  • Male
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / adverse effects
  • Nephritis / drug therapy*
  • Nephritis / etiology
  • Proteinuria / drug therapy
  • Proteinuria / etiology
  • ROC Curve
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Enzyme Inhibitors
  • Glucocorticoids
  • Mycophenolic Acid