Zipfel Complement and Kidney Disease

1. Auflage 2006
ISBN: 978-3-7643-7428-0
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 236 Seiten

Reihe: Progress in Inflammation Research

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney.
A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

Autoren/Hrsg.

Zipfel, Peter F

Inhaltsverzeichnis

1;Contents;6
2;Abbreviations;8
3;List of contributors;9
4;Preface;13
5;The complement system in renal diseases;15
5.1;Introduction;15
5.2;Hypocomplementemia in GN;15
5.3;Complement activation fragments in circulation;16
5.4;Complement deposits in glomeruli;17
5.5;Immune complex diseases and complement;17
5.6;Deficiencies of complement components and GN;18
5.7;Antibodies against complement components;19
5.8;Complement in SLE and lupus nephritis;22
5.9;IgA nephropathy and anti-mesangial cell proliferation;23
5.10;GN associated with infection;23
5.11;Membranous nephropathy;24
5.12;Tubulointerstitial disease and complement system;25
5.13;Complement, renal transplant and ischemia/reperfusion injury;26
5.14;Complement activation in cholesterol crystal emboli disease;27
5.15;References;27
6;Complement in renal transplantation;33
6.1;Introduction;33
6.2;Complement and renal transplantation;33
6.3;Role of complement in renal I/R injury;34
6.4;Complement in hyperacute rejection;36
6.5;Complement in allograft rejection;37
6.6;Locally synthesized C3 in allograft rejection;38
6.7;Complement regulates the immune response in allograft rejection;39
6.8;C4d in allograft rejection;40
6.9;Clinical implications;41
6.10;Conclusions;42
6.11;References;42
7;C1q and the glomerulonephritides: therapeutic approaches for the treatment of complement- mediated kidney diseases;50
7.1;Introduction;50
7.2;C1q deposition patterns in human glomerulonephritis;51
7.3;Complement-mediated damage in animal models of glomerulonephritis;51
7.4;C1q in glomerulonephritis;53
7.5;Anti-C1q antibodies;54
7.6;Therapeutic options;55
7.7;References;57
8;Complement deficient mice as model systems for kidney diseases;61
8.1;Introduction;61
8.2;Mouse strains with targeted deletion of complement components;61
8.3;Phenotypes of complement-deficient mice;63
8.4;Models of renal disease in which complement-deficient mice have been utilized;64
8.5;Conclusions;69
8.6;References;70
9;Non-Shiga toxin-associated hemolytic uremic syndrome;76
9.1;Definition;76
9.2;Pathology;76
9.3;Non-Stx-HUS;79
9.4;References;89
10;Role of complement and Factor H in hemolytic uremic syndrome;95
10.1;Introduction;95
10.2;HUS: the disease;99
10.3;Complement and aHUS;99
10.4;aHUS-associated Factor H gene mutations;100
10.5;Structure and function of Factor H;102
10.6;Autoantibodies to Factor H in aHUS patients;109
10.7;Mutations in other complement regulatory proteins: Factor I and MCP ( CD46);110
10.8;Conclusions;110
10.9;References;113
11;Genetic testing in atypical HUS and the role of membrane cofactor protein ( MCP; CD46) and Factor I;120
11.1;Introduction;120
11.2;Atypical HUS;120
11.3;Membrane cofactor protein;121
11.4;Function of MCP;121
11.5;MCP and HUS;123
11.6;Factor I;125
11.7;Implications of the association between MCP, Factor I and HUS;126
11.8;Clinical evaluation of the patient with aHUS;128
11.9;Molecular evaluation of Factor H, MCP and Factor I;129
11.10;Summary;131
11.11;References;132
12;Towards a new classification of hemolytic uremic syndrome;137
12.1;Introduction;137
12.2;Clinical features;137
12.3;Pathogenesis;139
12.4;HUS-associated mutations;141
12.5;Remarks to genetics and phenotype;146
12.6;References;150
13;Therapeutic strategies for atypical and recurrent hemolytic uremic syndromes ( HUS);157
13.1;Introduction;157
13.2;Alternative hypothesis of Factor H involvement;159
13.3;Recommendations for therapy of recurrent/aHUS;160
13.4;Recommendations for mode of plasma therapy;162
13.5;Recommendations for plasma volume;162
13.6;Choice of plasma;164
13.7;Risk of pathogen transmission due to plasma therapy;164
13.8;Risks of plasma infusion;164
13.9;Risks of plasma exchange;165
13.10;Blood pressure control;165
13.11;High viscosity;165
13.12;Coagulation;166
13.13;Transplantation;166
13.14;CD46-associated HUS;166
13.15;Transplantation of liver and combined simultaneous liver and kidney transplantation;166
13.16;Complement inhibitors;167
13.17;Conclusions;168
13.18;References;168
14;Complement defects in children which result in kidney diseases: diagnosis and therapy;172
14.1;Introduction;172
14.2;The complement system;173
14.3;Kidney diseases as result of complement defects in children;177
14.4;Appendix;183
14.5;Diagnosis and therapy;187
14.6;Summary;193
14.7;References;196
15;The role of complement in membranoproliferative glomerulonephritis;205
15.1;Introduction;205
15.2;Membranoproliferative glomerulonephritis: the disease;205
15.3;Type I membranoproliferative (mesangiocapillary) glomerulonephritis;206
15.4;Type II membranoproliferative glomerulonephritis;206
15.5;The alternative pathway as an essential part of complement;207
15.6;Regulation and regulators;209
15.7;Site of action and regulation;209
15.8;Expression of complement regulators on kidney cells and surfaces;211
15.9;Dysregulation of the alternative pathway results in membranoproliferative glomerulonephritis;214
15.10;Defective Factor H expression or deregulated function of Factor H;214
15.11;Factor H gene mutations observed in patients with defective secretion;215
15.12;Mutations that result in a secreted but functionally defective protein;216
15.13;Autoantibodies that inactivate the regulatory function of Factor H;217
15.14;Animal models;217
15.15;C3 nephritic factor, an autoantibody that inactivates the alternative complement pathway convertase C3bBb;219
15.16;Pathomechanisms;220
15.17;Outlook: diagnosis, treatment and prognosis for transplanted kidneys;221
15.18;Conclusions;222
15.19;References;222
16;The experience of a patient advocacy group;228
16.1;Introduction;228
16.2;The Foundation for Children with Atypical HUS;228
16.3;Advocacy, education and support;228
16.4;Our world;229
16.5;Support system rationale;231
16.6;The child’s/adolescent’s reality;232
16.7;Support system;233
16.8;The parent speaks;234
16.9;To raise a resilient child;234
16.10;Professional lifeline;235
16.11;In conclusion;236
17;Index;237