ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1557

Myeloperoxidase Immunohistochemical Staining and Response to Eculizumab in a Pediatric Patient with Dense Deposit Disease

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Blatt, Neal B., Beaumont Health, Royal Oak, Michigan, United States
  • Wickman, Larysa T., Beaumont Health, Royal Oak, Michigan, United States
  • Zhang, Ping L., Beaumont Health, Royal Oak, Michigan, United States
Introduction

Previous studies have demonstrated residual complement mediated deposits in repeat renal biopsies of patients with C3 glomerulopathies (Dense deposit disease (DDD) and C3 glomerulonephritis) following eculizumab treatment despite clinical improvement. With the residual complement deposition, it is often difficult to determine whether there is a reduced complement mediated endothelial cell injury. Herein, we report the use of myeloperoxidase (MPO) immunohistochemical staining to show decreased glomerular endothelial cell injury in a pediatric patient with DDD on chronic eculizumab therapy.

Case Description

Our patient was diagnosed with DDD by renal biopsy when he was 5 years old after presenting with a serum creatinine of 5.2 mg/dL, a urine protein to creatinine ratio of 2.5, and a complement C3 level of 50 mg/dL. Functional complement testing showed the presence of C3 and C5 nephritic factors. He was treated with eculizumab (600 mg every 2 weeks) and azathioprine, and over the course of 6 months, his serum creatinine, proteinuria, and complement C3 levels returned to normal. After weaning the frequency of his eculizumab infusions, he experienced a flare of DDD 15 months after initial presentation with a serum creatinine of 3.6 mg/dL, urine protein to creatinine ratio of 7, and complement C3 level of 76 mg/dL. He was re-dosed with eculizumab (600 mg every 2 weeks) with a rapid response to treatment. He had normalization of his serum creatinine to pre-flare levels within 6 months. Since then he has been maintained on eculizumab infusions (600 mg every 4 weeks) along with mycophenolate mofetil. A second kidney biopsy was performed after 3 years of treatment with eculizmab to evaluate response to treatment. The biopsy showed some residual features of dense deposit disease including C3 complement deposition. To evaluate if eculizumab blocked complement mediated injury on glomerular endothelial cells, MPO staining of his initial and repeat biopsy was performed: his initial biopsy revealed diffuse endothelial staining for MPO along glomerular endothelium and the repeat biopsy showed either no MPO staining or weak MPO staining in the glomerular endothelium.

Discussion

In this case, we find that MPO immunohistochemical staining may be useful for monitoring the response to complement blockade in patients with DDD.