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The Role of Complement in Disease

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Pediatric Kidney Disease

Abstract

Inflammatory renal tissue injury is associated with complement activation, either immune-mediated (e.g. immune complex nephritis, IgA nephropathy, humoral graft rejection), as a consequence of complement dysregulation (e.g. aHUS, STEC HUS, C3G/MPGN) or upon reperfusion of the ischemic transplant. Local synthesis of complement proteins contributes to the disease process. In the last years, modern complement analysis in body fluids and biopsies, going far beyond C3 and C4, has not only significantly enhanced our current understanding of the disease process, but also allowed for a more precise differential diagnosis and adds to early recognition of patients at risk for renal graft rejection. Consequently, complement-targeting therapy has been successfully introduced in patients with complement-mediated aHUS and shows first promising results in other inflammatory kidney disorders such as ANCA vasculitis, C3G/MPGN, post-transplant TMA and AMR.

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Abbreviations

aHUS:

Atypical hemolytic uremic syndrome

AMR:

Antibody-mediated rejection

ANCA:

Anti-neutrophil cytoplasmic antibodies

AP:

Alternative pathway

C3G:

C3 glomerulopathy

C3NeF:

C3 nephritic factor

CFB:

Complement factor B

CFH:

Complement factor H

CFHR:

Complement factor H related protein

CFI:

Complement factor I

CP:

Classical pathway

CR1:

Complement receptor 1 (CD35)

CR2:

Complement receptor 2 (CD21)

DAF:

Decay accelerating factor (CD55)

DDD:

Dense deposit disease

DSA:

Donor specific antibodies

ESRD:

End-stage renal disease

HAE 1/2:

Hereditary angioedema type 1/2

IgA-N:

IgA nephropathy

LP:

Lectin pathway

MAC:

Membrane attack complex (C5b-9)

MCP:

Membrane cofactor protein (CD46)

MPGN:

Membranoproliferative glomerulonephritis

PI:

Plasma infusion

PLEX:

Plasma exchange

PNH:

Paroxysmal nocturnal hemoglobinuria

SCR:

Short consensus repeat

STEC HUS:

Shiga toxin producing E. coli HUS

THBD:

Thrombomodulin (CD141)

TMA:

Thrombotic microangiopathy

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Authors and Affiliations

  1. Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Christoph Licht

  2. Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany

    Michael Kirschfink

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  1. Christoph Licht
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  2. Michael Kirschfink
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Correspondence to Christoph Licht .

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  1. Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Denis F. Geary

  2. Division of Pediatric Nephrology, University of Heidelberg, Heidelberg, Germany

    Franz Schaefer

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Licht, C., Kirschfink, M. (2016). The Role of Complement in Disease. In: Geary, D., Schaefer, F. (eds) Pediatric Kidney Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-52972-0_23

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