Abstract
Background
C3 glomerulonephritis (C3GN) can be a devastating disease with poor response to immunosuppressive therapy. Complement inhibition with eculizumab has had equivocal results in patients with C3GN.
Case-Diagnosis/Treatment
We report a case of a 6-year-old boy with C3GN presenting with nephrotic syndrome, severe hypertension and impaired kidney function. He did not respond to initial treatment with prednisone and mycophenolate (mofetil and sodium), and subsequent treatment with standard dosing of eculizumab. Pharmacokinetic studies identified a lack of eculizumab exposure and subsequent intensification of treatment with weekly dosing of eculizumab led to significant clinical improvement: his kidney function normalized, hypertension (weaned off 3 antihypertensive drugs), edema and proteinuria improved. Additionally, exposure to mycophenolic acid (MPA), active metabolite of mycophenolate, determined by area under the concentration–time curve of MPA was low throughout, despite significant dosing escalation.
Conclusions
This case report demonstrates that individualized therapy guided by therapeutic drug monitoring might be needed in patients with nephrotic range proteinuria treated with eculizumab and mycophenolate (mofetil and sodium), an important finding that needs to be considered for further treatment trials.
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Acknowledgements
We would like to acknowledge Arnaud Bonnefoy from the Specialized Biochemistry Lab at CHU Sainte-Justine, Montreal, Canada as well as Dr. Benjamin Jung and Dr. Lusia Sepiashvilli, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada, for their assistance with the organization and performance of specialized complement and eculizumab levels testing.
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MRK drafted, reviewed and revised the manuscript. MRK, CL and CWT contributed to the conceptualizing, design of the case report and critically reviewed the manuscript. EC and JT contributed their expertise on key concepts of therapeutic drug monitoring and critically reviewed the manuscript. RC contributed pathology interpretation, representative images from the patient’s pathology specimen for the manuscript figure and critically reviewed the manuscript. All authors critically reviewed the manuscript and approved the final manuscript as submitted.
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Riedl Khursigara, M., Chung, E., Tjon, J. et al. Utilizing therapeutic drug monitoring to optimize therapy with eculizumab and mycophenolate mofetil in a child with C3 glomerulonephritis. Pediatr Nephrol 38, 3483–3487 (2023). https://doi.org/10.1007/s00467-023-05927-9
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DOI: https://doi.org/10.1007/s00467-023-05927-9