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Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease?

Rojas-Rivera J, Fernández-Juárez G, Praga M - Clin Kidney J (2015)

Bottom Line: In this issue, two clinical studies of crescentic IgAN are presented.The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression.Both studies broaden our approach to patients with aggressive forms of IgAN.

View Article: PubMed Central - PubMed

Affiliation: Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario Fundación Jiménez Díaz , Madrid , Spain.

ABSTRACT
A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.

No MeSH data available.


Related in: MedlinePlus

Current therapeutic alternatives for crescentic IgA nephropathy. ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; CS, corticosteroids; IgA, immunoglobulin A nephropathy; MMF, mycophenolate mofetil; PE, plasma exchange; RTX, rituximab.
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SFV095F2: Current therapeutic alternatives for crescentic IgA nephropathy. ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; CS, corticosteroids; IgA, immunoglobulin A nephropathy; MMF, mycophenolate mofetil; PE, plasma exchange; RTX, rituximab.

Mentions: Due to the role of complement in the pathogenesis of IgAN, anti-complement therapies could have a place in the treatment of IgAN, particularly in aggressive cases resistant to currently recommended therapies [6]. Positive responses to eculizumab have been reported in complement-mediated glomerulonephritis [33, 34], and the effectiveness of blocking C5a receptors in ANCA vasculitis is now being evaluated by clinical trials [35]. In all these diseases, abnormal activation of complement plays an important role as initiator and amplifier of kidney damage [36–38]. Serum levels of C5b-9 complex, a promising biomarker to monitor complement activation and the response to eculizumab in atypical haemolytic uremic syndrome cases [39], were not measured in this case. Whether the improvement in renal function may have been more complete and sustained with longer eculizumab treatment and if measurement of serum C5b-9 levels could contribute to monitor both disease activity and response to therapy are interesting questions that need further studies. However, the high cost of eculizumab therapy is an important factor to be considered. Larger series of patients with longer follow-up and, ideally, controlled clinical trials comparing eculizumab with other therapies in aggressive types of IgAN are needed. Only such studies may offer solid conclusions about the possible role of eculizumab in rapidly progressive IgAN. Figure 2 shows the current therapeutic alternatives for crescentic IgAN.Fig. 2.


Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease?

Rojas-Rivera J, Fernández-Juárez G, Praga M - Clin Kidney J (2015)

Current therapeutic alternatives for crescentic IgA nephropathy. ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; CS, corticosteroids; IgA, immunoglobulin A nephropathy; MMF, mycophenolate mofetil; PE, plasma exchange; RTX, rituximab.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581398&req=5

SFV095F2: Current therapeutic alternatives for crescentic IgA nephropathy. ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; CS, corticosteroids; IgA, immunoglobulin A nephropathy; MMF, mycophenolate mofetil; PE, plasma exchange; RTX, rituximab.
Mentions: Due to the role of complement in the pathogenesis of IgAN, anti-complement therapies could have a place in the treatment of IgAN, particularly in aggressive cases resistant to currently recommended therapies [6]. Positive responses to eculizumab have been reported in complement-mediated glomerulonephritis [33, 34], and the effectiveness of blocking C5a receptors in ANCA vasculitis is now being evaluated by clinical trials [35]. In all these diseases, abnormal activation of complement plays an important role as initiator and amplifier of kidney damage [36–38]. Serum levels of C5b-9 complex, a promising biomarker to monitor complement activation and the response to eculizumab in atypical haemolytic uremic syndrome cases [39], were not measured in this case. Whether the improvement in renal function may have been more complete and sustained with longer eculizumab treatment and if measurement of serum C5b-9 levels could contribute to monitor both disease activity and response to therapy are interesting questions that need further studies. However, the high cost of eculizumab therapy is an important factor to be considered. Larger series of patients with longer follow-up and, ideally, controlled clinical trials comparing eculizumab with other therapies in aggressive types of IgAN are needed. Only such studies may offer solid conclusions about the possible role of eculizumab in rapidly progressive IgAN. Figure 2 shows the current therapeutic alternatives for crescentic IgAN.Fig. 2.

Bottom Line: In this issue, two clinical studies of crescentic IgAN are presented.The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression.Both studies broaden our approach to patients with aggressive forms of IgAN.

View Article: PubMed Central - PubMed

Affiliation: Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario Fundación Jiménez Díaz , Madrid , Spain.

ABSTRACT
A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.

No MeSH data available.


Related in: MedlinePlus