Lupus Nephritis

by Lewis, Edmund J.; Schwartz, Melvin M.; Korbet, Stephen M.; Chan, Tak Mao

• ISBN13: 9780199568055
• ISBN10: 0199568057
• Edition: 2nd
• Format: Paperback
• Copyright: 2010-12-01
• Publisher: Oxford University Press

Summary

Severe inflammation of the kidney can indicate the serious, negative prognosis of lupus nephritis when present in conjunction with systemic lupus erythematosus (SLE), a chronic autoimmune connective tissue disease that can affect any part of the body, most often harming the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. This book pulls together in one comprehensive reference the current knowledge regarding the inherited and immunologic abnormalities that have been identified in SLE, with specific reference to the development of renal disease and the way in which these factors may impact upon the chronic care of these patients. Since publication of the first edition in 1999, the discipline of medicine has experienced some revolutionary changes in the way drugs are used to treat to immune system diseases. On the basis of careful analysis of physical make-up, the immune system, and microscopic features of the human body, it has become clear that multiple components of the immune system are responsible for renal injury and that any given patient can experience a combination of these mechanisms. With this in mind, specific therapies can be tested, and drugs that interrupt the immune response in highly specific ways are being scrutinized for their value in lupus nephritis. This new edition reflects the updated methods of classification and advances in treatment options for SLE, and covers recent clinical trials to help treat patients using the most up-to-date knowledge available. It takes a practical approach throughout, and will be of interest to those working with patients with lupus nephritis, and those who manage their everyday care.

Author Biography

Edmund J. Lewis, M.D. is the Muehrcke Family Professor of Nephrology at Rush University Medical Center. Much of his career has been devoted to the study of immunopathologic mechanisms of glomerular disease, particularly lupus nephritis. He was an active participant in the International Study of Kidney Disease in Children (ISKDC), and as a member of the Pathology Committee he co-authored the first World Health Organization Classification of lupus nephritis. This led him to organize the Collaborative Study Group, whose initial study of plasmapheresis in severe lupus nephritis led to many important observations regarding clinical and histologic features which determine response to therapy in this patient population. In 2007, Dr. Lewis received the Belding Scribner Award of the American Society of Nephrology "for outstanding contributions to nephrology in the area of clinical practice and patient care".


Professor Melvin M. Schwartz completed his M.D. at the University of Minnesota in 1967, before taking a Pathology Residency at the Mallory Institute of Pathology between 1968 and1971, and completing a Renal Pathology Fellowship, also at the Mallory Institute of Pathology, in 1973. He became Professor Pathology at Rush University Medical Center in1984.


Stephen M. Korbet graduated from Rush Medical College in 1979 and did his internship, residency and Fellowship training at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois. He is board certified in Internal Medicine and Nephrology. Dr. Korbet has received many prestigious honors and awards. He holds the endowed chair of the "Lester and Muriel Anixter Professor of Nephrology" at Rush Medical College. He is also currently the Medical Director of Circle Medical Management Dialysis Facility in Chicago as well as the Division Chief of the Section of Nephrology, Rush University Medical Center. Chicago, IL He has also been actively involved in clinical research involving kidney disease and dialysis since 1986 until the present date.

Tak Mao Daniel Chan graduated from the University of Hong Kong in 1985, and received training in nephrology and internal medicine in Hong Kong and at the Guy's Hospital in London, U.K. He is a Fellow of the Royal Colleges of Physicians in U.K. He is currently Personal Chair and Yu Foundation Endowed Professor in Nephrology at the Department of Medicine, and the Associated Dean at the Li Ka Shing Faculty of Medicine, University of Hong Kong. He was President of the Asian Pacific Society of Nephrology from 2008 to 2010. He is an Executive Committee member of the Asian Society of Transplantation, and has previously served as President of the Hong Kong Society of Transplantation. He pioneered the use of mycophenolate mofetil in the treatment of severe lupus nephritis. In addition to the treatment and immuno-pathogenesis of lupus nephritis, his other research interests include viral hepatitis in patients with renal failure.

Table of Contents

Contributors	p. xi
Abbreviations	p. xiii
Clinical manifestations of lupus nephritis	p. 1
Introduction	p. 1
Historical perspective	p. 1
Definitions of lupus	p. 3
Clinical factors in the genesis of lupus	p. 5
Sex and age in the presentation of lupus	p. 8
Differential diagnosis	p. 9
The clinical manifestations of lupus	p. 10
Clinicopathological correlations	p. 22
Summing up	p. 23
Autoantibodies and lupus nephritis	p. 35
Introduction	p. 35
Anti-DNA antibodies in lupus nephritis	p. 37
Anti-DNA antibodies and mechanisms of glomerular damage	p. 39
The importance of DNA-histone complexes	p. 44
Antibodies to protein components of chromatin	p. 45
Antibodies to other nuclear antigens	p. 46
Antibodies to cytoplasmic antigens	p. 47
Antibodies to complement component Clq	p. 48
Antiphospholipid (APL) antibodies	p. 48
The origin of pathogenic autoantibodies in SLE	p. 49
Conclusions	p. 50
T cells and B cells in lupus nephritis	p. 59
Introduction	p. 59
Initiation of nephritogenic autoimmune responses	p. 59
T cells and cellular immunity in lupus nephritis	p. 64
B cells and humoral immunity in lupus nephritis	p. 69
Summary and conclusion	p. 73
The many effects of complement in lupus nephritis	p. 83
Why complement in human SLE?	p. 86
Mouse models of human SLE	p. 88
Functional studies of complement in experimental lupus models	p. 89
What we've learned from animals can be used in the treatment of humans	p. 93
Pathways of cellular adaptive immunity in autoimmune crescentic glomerulonephritis and lupus nephritis	p. 105
Introduction	p. 105
T helper pathways in experimental crescentic GN	p. 106
T helper cells in autoimmune human GN	p. 110
T regulatory cells in crescentic GN	p. 113
NK cells and NKT cells in crescentic GN and lupus	p. 114
Dendritic cells, TLRs, and type I interferons	p. 116
Conclusion	p. 118
Pathology, pathogenesis, and clinical features of severe lupus nephritis	p. 129
The definition of severe lupus nephritis (SLN)	p. 129
The glomerular pathology of SLN	p. 136
The pathogenesis of SLN	p. 148
Clinical features and prognosis of SLN	p. 153
Insights from the Lupus Nephritis Collaborative Study Group	p. 153
Insights from the International Society of Nephrology and Renal Pathology Society classification	p. 157
Why do the clinical observations differ?	p. 159
Conclusion	p. 161
Lupus membranous nephropathy	p. 169
Introduction	p. 169
Historical perspective on lupus membranous nephropathy	p. 169
Pathogenesis	p. 170
Renal biopsy features and classification	p. 174
Clinical presentation	p. 177
Prognosis of lupus membranous nephropathy	p. 178
Supportive therapies	p. 180
Immunosuppressive therapies	p. 182
Experimental therapies	p. 187
Current treatment recommendations	p. 189
Lupus podocytopathy	p. 199
Introduction	p. 199
Clinical association of active systemic disease of lupus with the onset of nephrotic syndrome	p. 200
Nephrotic syndrome and acute renal failure	p. 203
Minimal change glomerulopathy: a manifestation of lupus	p. 204
Mesangial lupus nephritis	p. 205
SLE and podocytopathy: not a coincidence	p. 206
Glomerular epithelial cell damage and the nephrotic syndrome	p. 207
Clinical recommendations	p. 208
Renal vascular involvement in SLE	p. 211
Introduction	p. 211
Immune complex deposits	p. 211
Noninflammatory necrotizing vasculopathy	p. 213
Inflammatory vasculitis	p. 216
Thrombotic vascular lesions	p. 218
Conclusions	p. 227
Mycophenolate mofetil as treatment in lupus nephritis	p. 237
Introduction	p. 237
Mycophenolate mofetil as induction treatment for lupus nephritis	p. 238
Mycophenolate mofetil as maintenance treatment for lupus nephritis	p. 242
Impact of mycophenolate mofetil treatment on renal and patient survival	p. 244
Mycophenolate mofetil and membranous lupus nephritis	p. 245
Effects of mycophenolic acid on resident kidney cells	p. 246
Other issues related to mycophenolate mofetil treatment	p. 246
Conclusions	p. 249
Lupus nephritis and pregnancy	p. 257
Introduction	p. 257
Numbers affected	p. 257
Fertility	p. 257
Normal renal physiological changes in pregnancy	p. 258
Lupus and pregnancy hormones	p. 258
Effect of pregnancy on lupus and renal disease	p. 259
Effect of lupus nephritis on pregnancy outcome	p. 261
Factors influencing pregnancy outcome	p. 262
Management	p. 265
Conclusion	p. 272
The treatment of severe proliferative lupus nephritis	p. 281
Introduction	p. 281
General considerations in developing a therapeutic plan for severe lupus nephritis	p. 282
Induction therapy for severe proliferative lupus nephritis	p. 284
Maintenance therapy for severe proliferative lupus nephritis	p. 295
Treatment of refractory severe lupus nephritis	p. 299
Treatment of renal and systemic relapses in severe lupus nephritis	p. 300
Special issues in treatment of severe lupus nephritis	p. 301
Summary of the therapy of severe lupus nephritis	p. 303
Index	p. 317
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