Agnes Hackl1, Jan U Becker2, Lisa M Körner3, Rasmus Ehren3, Sandra Habbig3, Eva Nüsken3, Kai-Dietrich Nüsken3, Kathrin Ebner3, Max C Liebau3,4,5, Carsten Müller6, Martin Pohl7, Lutz T Weber3. 1. Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany. agnes.hackl@uk-koeln.de. 2. Institute of Pathology, University Hospital of Cologne, Cologne, Germany. 3. Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany. 4. Nephrology Research Laboratory, Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany. 5. Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany. 6. Department of Therapeutic Drug Monitoring, Centre of Pharmacology, University Hospital of Cologne, Cologne, Germany. 7. Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - Faculty of Medicine, University of Freiburg Germany, Freiburg, Germany.
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.
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.
Entities:
Keywords:
Cut-off of eMPA-AUC0-12h; Mechanism of action; Mycophenolic acid; Pre-dose level; Therapeutic drug monitoring
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