Myeloperoxidase Immunohistochemical Staining and Response to Eculizumab in a Pediatric Patient with Dense Deposit Disease.
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.
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.
In this case, we find that MPO immunohistochemical staining may be useful for monitoring the response to complement blockade in patients with DDD.
Blatt NB, Wickman LT, Zhang PL. Myeloperoxidase immunohistochemical staining and response to eculizumab in a pediatric patient with dense deposit disease. Paper presented at: The Annual Meeting of the American Society of Nephrology; 2021 Nov 4-7; Virtual.