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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.


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Course of the disease.
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SFV076F2: Course of the disease.

Mentions: Because of the rapid loss of renal function and the acute changes on biopsy with no evidence of chronic damage it was elected to treat him with prednisolone 40 mg daily and cyclophosphamide 100 mg (1.5 mg/kg) [9]. He was also anticoagulated with warfarin and low molecular weight heparin. Despite this, renal function deteriorated further. He was, therefore, given three daily pulses of methylprednisolone 500 mg followed by five plasma exchanges (40 mL/kg). This did not result in any improvement. As a last resort—and without any direct proof of complement involvement—we decided to treat with eculizumab. Four weekly doses of 900 mg were administered intravenously followed by a single dose of 1200 mg accompanied throughout by penicillin. Immediately after the first dose of eculizumab a remarkable improvement in renal function was evident. After 3 months cyclophosphamide was replaced with azathioprine and the dose of prednisolone was tapered. The course is shown in Figure 2.Fig. 2.


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

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

Course of the disease.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

SFV076F2: Course of the disease.
Mentions: Because of the rapid loss of renal function and the acute changes on biopsy with no evidence of chronic damage it was elected to treat him with prednisolone 40 mg daily and cyclophosphamide 100 mg (1.5 mg/kg) [9]. He was also anticoagulated with warfarin and low molecular weight heparin. Despite this, renal function deteriorated further. He was, therefore, given three daily pulses of methylprednisolone 500 mg followed by five plasma exchanges (40 mL/kg). This did not result in any improvement. As a last resort—and without any direct proof of complement involvement—we decided to treat with eculizumab. Four weekly doses of 900 mg were administered intravenously followed by a single dose of 1200 mg accompanied throughout by penicillin. Immediately after the first dose of eculizumab a remarkable improvement in renal function was evident. After 3 months cyclophosphamide was replaced with azathioprine and the dose of prednisolone was tapered. The course is shown in Figure 2.Fig. 2.

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