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Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

Ring T, Pedersen BB, Salkus G, Goodship TH - Clin Kidney J (2015)

Bottom Line: He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months.However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes.We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology , Aalborg University Hospital , Aalborg , Denmark.

ABSTRACT
IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

No MeSH data available.


Related in: MedlinePlus

(A) Glomerulus with a cellular crescent in a first renal biopsy; ×20, PAS. (B) Segmental glomerulosclerosis and atrophy of tubuli and fibrosis of interstitium in a second renal biopsy 11 months later, ×20, PAS (left) and IgA immunofluorescence (right).
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SFV076F1: (A) Glomerulus with a cellular crescent in a first renal biopsy; ×20, PAS. (B) Segmental glomerulosclerosis and atrophy of tubuli and fibrosis of interstitium in a second renal biopsy 11 months later, ×20, PAS (left) and IgA immunofluorescence (right).

Mentions: A biopsy (Figure 1A) revealed epithelial crescents in 6 of 14 glomeruli, mesangial hyperplasia, endocapillary hypercellularity and deposition of both IgA (++++/4+) and C3 (+++/4+) on immunofluorescence (M1 S0 E1 T0 according to Oxford classification).Fig. 1.


Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

Ring T, Pedersen BB, Salkus G, Goodship TH - Clin Kidney J (2015)

(A) Glomerulus with a cellular crescent in a first renal biopsy; ×20, PAS. (B) Segmental glomerulosclerosis and atrophy of tubuli and fibrosis of interstitium in a second renal biopsy 11 months later, ×20, PAS (left) and IgA immunofluorescence (right).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581393&req=5

SFV076F1: (A) Glomerulus with a cellular crescent in a first renal biopsy; ×20, PAS. (B) Segmental glomerulosclerosis and atrophy of tubuli and fibrosis of interstitium in a second renal biopsy 11 months later, ×20, PAS (left) and IgA immunofluorescence (right).
Mentions: A biopsy (Figure 1A) revealed epithelial crescents in 6 of 14 glomeruli, mesangial hyperplasia, endocapillary hypercellularity and deposition of both IgA (++++/4+) and C3 (+++/4+) on immunofluorescence (M1 S0 E1 T0 according to Oxford classification).Fig. 1.

Bottom Line: He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months.However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes.We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology , Aalborg University Hospital , Aalborg , Denmark.

ABSTRACT
IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

No MeSH data available.


Related in: MedlinePlus