Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports

Hassib Chehade,Daniel Teta,Gabriella Guzzo,Ivy A Rosales,Samuel Rotman,Amita Sharma,Manuel Pascual,Salima Sadallah,Giuseppe Pantaleo,Nina Tolkoff-Rubin,Francois Cachat

doi:10.3389/fmed.2021.663258

Abstract

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood. The implication of the alternative complement pathway and the potential benefits of C5 blockade have been recently highlighted, in particular in the presence of a C3 Nephritic Factor (C3Nef), anti-Factor B or H autoantibodies. We report two children with severe APIGN, successfully treated with eculizumab. The first patient presented a severe form of APIGN with advanced renal failure and anuria, associated with a decreased level of C3 and an increased level of soluble C5b-9, in the presence of a C3NeF autoantibody. The second case had a severe oliguric APIGN associated with low C3 level. Kidney biopsy confirmed the diagnosis of APIGN in both cases. Eculizumab allowed full renal function recovery and the avoidance of dialysis in both cases. In conclusion, the alternative and terminal complement pathways activation might be common in PIGN, and in severe cases, eculizumab might help.

Highlights

Acute post-infectious glomerulonephritis (APIGN) represents the major cause of acute glomerulonephritis in children worldwide
We have recently reported the first case of successful reversal of acute and severe PIGN using eculizumab, an anti-C5 monoclonal antibody that blocks terminal complement activation, in an 8year-old child with Acute post-infections glomerulonephritis (APIGN) requiring dialysis [11]
Low C3 level is observed in almost 90% of biopsy-proven APIGN, whereas levels of the classical complement activation pathway such as

Summary

INTRODUCTION

Acute post-infectious glomerulonephritis (APIGN) represents the major cause of acute glomerulonephritis in children worldwide. It is often secondary to group A streptococcal infection [1]. In 2005, the World Health Organization estimated the number of new annual cases at 472,000, with a mortality of 5,000 cases per year [2]. The vast majority of cases occurs in developing countries with an annual incidence of 24/100,000 inhabitants [2]. APIGN harbors a good prognosis, it is rarely associated to permanent mild urinalysis abnormalities, acute renal failure, or even end-stage kidney disease [3,4,5]

Blockade in Children With APIGN

DISCUSSION

ETHICS STATEMENT