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

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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.

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Abbreviations

ACEi:

Angiotensin-converting enzyme inhibitors

ARB:

Angiotensin II receptor blockers

BSA:

Body surface area

CI:

Confidence interval

CKD:

Chronic kidney disease

ESRD:

End-stage renal disease

GTP:

Guanosine-5′-triphosphate

HSP:

Henoch-Schönlein purpura

HSPN:

Henoch-Schönlein purpura nephritis

IgACI:

Immunoglobulin A circulating immune complex

IMPDH:

Inosine-5′-monophosphate dehydrogenase

IS therapy:

Immunosuppressive therapy

MMF:

Mycophenolate mofetil

MP:

Methylprednisolone

MPA-C0 :

Pre-dose level of mycophenolic acid

eMPA-AUC0-12h :

Estimated mycophenolic acid–area under the concentration versus time curve

NA:

Not applicable

PU:

Proteinuria

RAAS:

Renin–angiotensin–aldosterone system

ROC:

Receiver operating characteristic

TDM:

Therapeutic drug monitoring

UTI:

Urinary tract infection

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Authors and Affiliations

  1. Pediatric Nephrology, Children’s and Adolescents’ Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany

    Agnes Hackl, Lisa M. Körner, Rasmus Ehren, Sandra Habbig, Eva Nüsken, Kai-Dietrich Nüsken, Kathrin Ebner, Max C. Liebau & Lutz T. Weber

  2. Institute of Pathology, University Hospital of Cologne, Cologne, Germany

    Jan U. Becker

  3. Nephrology Research Laboratory, Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany

    Max C. Liebau

  4. Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany

    Max C. Liebau

  5. Department of Therapeutic Drug Monitoring, Centre of Pharmacology, University Hospital of Cologne, Cologne, Germany

    Carsten Müller

  6. Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - Faculty of Medicine, University of Freiburg Germany, Freiburg, Germany

    Martin Pohl

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  1. Agnes Hackl
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Correspondence to Agnes Hackl.

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Hackl, A., Becker, J.U., Körner, L.M. et al. Mycophenolate mofetil following glucocorticoid treatment in Henoch-Schönlein purpura nephritis: the role of early initiation and therapeutic drug monitoring. Pediatr Nephrol 33, 619–629 (2018). https://doi.org/10.1007/s00467-017-3846-6

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