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Abstract: PO1555

Utilizing Pharmacokinetic Studies to Optimize Therapy in a Child with C3 Glomerulonephritis and Nephrotic Syndrome: A Precision Medicine Approach

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Riedl Khursigara, Magdalena, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Noone, Damien Gerard, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Radhakrishnan, Seetha, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Tjon, James Anthony, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Chami, Rose, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Parekh, Rulan S., The Hospital for Sick Children, Toronto, Ontario, Canada
  • Langlois, Valerie, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Licht, Christoph, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Teoh, Chia Wei, The Hospital for Sick Children, Toronto, Ontario, Canada
Introduction

C3 glomerulonephritis (C3GN) is caused by complement alternative pathway dysregulation, has no definitive treatment and is characterized by progression to ESRD. Terminal complement blockade has successfully been used especially in patients with elevated C5b-9 levels.

Case Description

We describe a 6 year old boy with C3GN, who presented with nephrotic syndrome, severe hypertension (4 anti-hypertensive medications) and acute kidney injury. Complement C3 level was 0.12 g/L (normal 0.8-1.5) with pos C3NeF and elevated C5b-9 levels (2135, normal <239ng/ml). Despite 6 months of treatment with steroid and MMF, he had ongoing nephrotic syndrome and worsening kidney function. He commenced on standard Eculizumab dosing. Despite 6 months of therapy, he had persistent severe hypertension, nephrotic syndrome requiring weekly albumin/furosemide infusions and worsening kidney function. Complement C3 levels remained low with elevated C5b-9 levels, suggesting sub-optimal terminal complement inhibition due to urinary loss. We confirmed sub-therapeutic plasma concentrations of eculizumab as free plasma eculizumab levels were low on day 7 (9, normal >99 ug/ml) and undetectable on days 10 and 14 post-infusion. Eculizumab frequency was subsequently increased to weekly with MPA-AUC guided adjustment of MMF dosing. Since then, his kidney function, C5b-9 levels (297ng/ml) and nephrotic syndrome improved significantly, leading to discontinuation of albumin/furosemide and anti-hypertensive medications.

Discussion

Use of pharmacokinetic studies can aid in individualized eculizumab treatment in C3GN patients with ongoing proteinuria and who failed to respond to standard dosing.