Pediatric nephrology (Berlin, Germany) · 2023
Utilizing therapeutic drug monitoring to optimize therapy with eculizumab and mycophenolate mofetil in a child with C3 glomerulonephritis.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
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Riedl Khursigara Magdalena, Chung Erin, Tjon James, Noone Damien, Chami Rose, Licht Christoph, Teoh Chia Wei
Аннотация
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.
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.