We are IntechOpen, the world's leading publisher of Open Access books Built by scientists, for scientists

4,100+

Open access books available

116,000+

International authors and editors

120M+

Downloads

Our authors are among the

Top 1%

most cited scientists

12.2%

Contributors from top 500 universities

Selection of our books indexed in the Book Citation Index in Web of Science™ Core Collection (BKCI)

## Interested in publishing with us? Contact book.department@intechopen.com

Numbers displayed above are based on latest data collected. For more information visit www.intechopen.com

## **Meet the editor**

Dr. Sharma S. Prabhakar is a distinguished nephrologist currently at Texas Tech University Health Sciences Center, where he is a tenured professor in the Departments of Medicine and Cell Physiology and Molecular Biophysics, and the Chief of Nephrology Division and Vice Chairman, Department of Medicine. He is an established researcher examining pathophysiologic mechanisms of

diabetic nephropathy and of insulin resistance in vitro and animal models. In the area of clinical research he initiated and is the principal investigator of a number of clinical studies. Dr. Prabhakar has over 100 publications including original articles, reviews, book chapters and published abstracts in prestigious journals, such as the American Journal of Physiology, Journal of American Society of Nephrology, and Kidney International. He has recently published a reference book entitled "Advances in the Pathogenesis of Diabetic Nephropathy". In recognition of his excellence in practice of medicine, Dr. Prabhakar was awarded an endowed chair by the University Medical Center. He is active in several professional societies and organizations and is the current President of American Federation for Medical Research.

Contents

**Foreword IX** 

**Part 1 Primary Glomerulopathies 1** 

Chapter 2 **Focal Segmental Glomerulosclerosis 25** 

Abdelaziz Elsanjak and Sharma S. Prabhakar

Dawinder S. Sohal and Sharma S Prabhakar

Chapter 3 **Membranoproliferative Glomerulonephritis 45**  Matthew C. Pickering and Joshua M. Thurman

Chapter 4 **Primary IgA Nephropathy: An Update in 2011 59**  Francois Berthoux and Amir Kamal Aziz

**Genetic Basis and Treatment Options 69** 

**Part 2 Infectious Glomerulopathies and Related Disorders 111** 

**Post-Infectious Streptococcal Glomerulonephritis 137** 

Chapter 6 **Rapidly Progressive Glomerulonephritis 95** 

Chapter 7 **Post-Infectious Glomerulonephritis 113** 

Chapter 8 *S. pyogenes* **Infections and Its Sequelae 125**  L. Guilherme, S. Freschi de Barros

W. Michael McShan and Roya Toloui

A.C. Tanaka, M.C. Ribeiro Castro and J. Kalil

Dimitrios Kirmizis, Aikaterini Papagianni and Francesco Paolo Schena

Chapter 1 **Membranous Nephropathy 3** 

Chapter 5 **IgA Nephropathy: Insights into** 

Maria Pia Rastaldi

Gurmeet Singh

Chapter 9 **Insights from Genomics on** 

**Preface XI** 

## Contents

### **Foreword XIII**

**Preface XV**

	- **Part 2 Infectious Glomerulopathies and Related Disorders 111**

X Contents


Contents VII

Chapter 22 **Mild Forms of Alport Syndrome: Hereditary** 

**Part 5 Miscellaneous Topics 437** 

Gertruida van Biljon

Toshihiko Ishimitsu

Chapter 23 **Nephrotic Syndrome** 

Chapter 24 **Blood Pressure Control** 

Han-Seung Yoon and Michael R. Eccles

**in Children – Studies from South Africa 439** 

**in Patients with Glomerulonephritis 455** 

**Nephropathy in the Absence of Extra-Renal Features 417** 

Daniel Fischman, Arvin Parvathaneni and Pramil Cheriyath

	- **Part 5 Miscellaneous Topics 437**

VI Contents

Chapter 10 **Atypical Clinical Manifestations of** 

Vincent Ho and Jason Chen

Toru Watanabe

Marco Zaffanello

Chapter 16 **Mixed Hematopoietic**

Chapter 17 **Differential Diagnosis**

Mitra Naseri

**Part 4 Glomerular Disease in** 

Chapter 19 **Diabetic Glomerulopathy 327**

Emiko Takeuchi

Chapter 14 **Lupus Glomerulonephritis 231**  Chi Chiu Mok

**Acute Poststreptococcal Glomerulonephritis 151** 

Chapter 11 **Hepatitis C Virus Associated Glomerulonephritis 169** 

Enrique Morales, Elena Gutierrez-Solis, Eduardo Gutierrez and Manuel Praga

Chapter 12 **Glomerular Pathology in Patients with HIV Infection 189** 

**Part 3 Vasculitis and Autoimmune Glomerulopathies 207** 

Chapter 13 **Henoch-Schönlein Purpura Nephritis in Childhood 209** 

Chapter 15 **Anti-Glomerular Basement Membrane Disease 251** Kouichi Hirayama and Kunihiro Yamagata

**Chimerism Allows Cure of Autoimmune** 

**of the Pulmonary-Renal Syndrome 291**

Chapter 18 **RPGN - Clinical Features, Treatment and Prognosis 299** 

**Metabolic and Systemic Conditions 325** 

Chapter 20 **Metabolic Syndrome Associated Kidney Damage 369**

Chapter 21 **Glomerulonephritis and the Cystic Fibrosis Patient 399** 

**Glomerulonephritis: Its Potential and Risks 277** 

Martin Kimmel, Niko Braun and Mark Dominik Alscher

Mahmoud Barazi, Harneet Kaur and Sharma Prabhakar

Hequn Zou, Yuxin Wang, Guimian Zou and Jianxin Wan

Daniel Fischman, Arvin Parvathaneni and Pramil Cheriyath


Foreword

Glomerulopathies - Etiology and Pathogenesis.

The study of the fundamental and clinical aspects of glomerular disease has expanded exponentially over the last several decades. Fresh insights into old clinico-pathological entities emerge frequently and continuously. New disease entities also arise as the sophistication of investigation expands. Novel disease-specific treatments are applied often with impressive results while older, more empiric therapeutic strategies are in a constant state of evaluation and re-evaluation. Thus a book dealing with recent advances in the field of glomerulopathies from both clinical and therapeutic aspects is a welcome addition to our knowledge base. *An Update on Glomerulopathies - Clinical and Treatment Aspects* builds on the background provided by An Update on

In 24 concise, focused and well-formulated chapters the broad scope of clinical and therapeutic aspects of primary and secondary glomerular disease is reviewed and updated. The Editor, Dr. Sharma Prabhakar has chosen both the topics and the authors wisely. The contributions will have great appeal and value to the practicing clinician who frequently must face diagnostic and management challenges in this arena of medicine. While not exhaustive in coverage, the topics included embrace an impressive breadth of clinical experience in these disorders. The contributions also examine contemporary issues in sufficient detail to serve as an excellent guide for the clinician as well as trainees in nephrology. *An Update on Glomerulopathies - Clinical and Treatment Aspects* illustrates how far we have come in our understanding of clinical issues in glomerular disease, but also shows how much more needs to be understood.

**Richard J. Glassock, MD, MACP** 

Laguna Niguel, California

USA

## Foreword

The study of the fundamental and clinical aspects of glomerular disease has expanded exponentially over the last several decades. Fresh insights into old clinico-pathological entities emerge frequently and continuously. New disease entities also arise as the sophistication of investigation expands. Novel disease-specific treatments are applied often with impressive results while older, more empiric therapeutic strategies are in a constant state of evaluation and re-evaluation. Thus a book dealing with recent advances in the field of glomerulopathies from both clinical and therapeutic aspects is a welcome addition to our knowledge base. *An Update on Glomerulopathies - Clinical and Treatment Aspects* builds on the background provided by An Update on Glomerulopathies - Etiology and Pathogenesis.

In 24 concise, focused and well-formulated chapters the broad scope of clinical and therapeutic aspects of primary and secondary glomerular disease is reviewed and updated. The Editor, Dr. Sharma Prabhakar has chosen both the topics and the authors wisely. The contributions will have great appeal and value to the practicing clinician who frequently must face diagnostic and management challenges in this arena of medicine. While not exhaustive in coverage, the topics included embrace an impressive breadth of clinical experience in these disorders. The contributions also examine contemporary issues in sufficient detail to serve as an excellent guide for the clinician as well as trainees in nephrology. *An Update on Glomerulopathies - Clinical and Treatment Aspects* illustrates how far we have come in our understanding of clinical issues in glomerular disease, but also shows how much more needs to be understood.

> **Richard J. Glassock, MD, MACP**  Laguna Niguel, California USA

Preface

knowledge from this reference book.

with current management strategies.

As the complexities of pathobiology of the glomerular diseases continue to unfold, the resultant scientific knowledge has lent itself to development of novel therapeutic targets and innovative preventive and therapeutic strategies. This book is a sequel to a similar one devoted to Etiology and Pathogenesis, and a broad discussion of advances in the clinical and treatment aspects of various glomerular disorders is the focus of this book. While most individual chapters serve as updates of clinical and treatment aspects of the respective glomerulopathies, they are by no means comprehensive discussion of these clincal conditions. The reader is referred to currents textbooks for the basic background clinical information of glomerulopathies and to enrich such

The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies and has six chapters. The first chapter is a rather comprehensive discussion on the clinical aspects of membranous nephropathy with a detailed review of the currently available treatment options. This is followed by a very exhaustive narrative of focal and segmental glomerulosclerosis with lucid illustrations. Membranoproliferative glomerulonephritis is a complex disorder which is also seen is several systemic conditions and is very elegantly discussed by Matthew Pickering et al. There are two chapters on IgA nephropathy, the most common glomerulopathy worldwide. Francois Berthoux et al. authored an excellent overall review of the clinical features and management of this condition, while Dimitrios Kirmizis et al. present a comprehensive review of the genetic determinants of IgA nephropathy. Finally, Maria Pia Rastaldi provides a crisp and clear discussion on the important subject of rapidly progressive glomerulonephritis

The second section is devoted to glomerulopathies complicating infectious conditions and includes six chapters. Gurmeet Singh authored a concise yet informative review on the postinfectious glomerulonephritis. In addition, there is a separate chapter on

## Preface

As the complexities of pathobiology of the glomerular diseases continue to unfold, the resultant scientific knowledge has lent itself to development of novel therapeutic targets and innovative preventive and therapeutic strategies. This book is a sequel to a similar one devoted to Etiology and Pathogenesis, and a broad discussion of advances in the clinical and treatment aspects of various glomerular disorders is the focus of this book. While most individual chapters serve as updates of clinical and treatment aspects of the respective glomerulopathies, they are by no means comprehensive discussion of these clincal conditions. The reader is referred to currents textbooks for the basic background clinical information of glomerulopathies and to enrich such knowledge from this reference book.

The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies and has six chapters. The first chapter is a rather comprehensive discussion on the clinical aspects of membranous nephropathy with a detailed review of the currently available treatment options. This is followed by a very exhaustive narrative of focal and segmental glomerulosclerosis with lucid illustrations. Membranoproliferative glomerulonephritis is a complex disorder which is also seen is several systemic conditions and is very elegantly discussed by Matthew Pickering et al. There are two chapters on IgA nephropathy, the most common glomerulopathy worldwide. Francois Berthoux et al. authored an excellent overall review of the clinical features and management of this condition, while Dimitrios Kirmizis et al. present a comprehensive review of the genetic determinants of IgA nephropathy. Finally, Maria Pia Rastaldi provides a crisp and clear discussion on the important subject of rapidly progressive glomerulonephritis with current management strategies.

The second section is devoted to glomerulopathies complicating infectious conditions and includes six chapters. Gurmeet Singh authored a concise yet informative review on the postinfectious glomerulonephritis. In addition, there is a separate chapter on the renal and non-renal sequelae of S pyogenes infections by Luiza Guilherme et al., while W. Michael McShan et al. provided a focused overview on the genomics of post streptococcal glomerulonephritis. The atypical clinical features of poststreptococcal glomerulonephritis are discussed in a chapter written by Toru Watanabe. Finally, there are two chapters that provide recent insights into glomerular complications of Hepatitis C and HIV infections respectively.

Preface XIII

USA

in a concise and clear manner the significance of and approaches to blood pressure

In summary, *An Update on Glomerulopathies - Clinical and Treatment Aspects* is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. While by no means this book replaces currently available textbooks in nephrology, it is the expectation of the Editor that it will form an excellent reference tool for practicing and academic nephrology community. The Editor expresses deep and sincere gratitude to all the authors for their valuable contributions which facilitated the prompt compilation of this invaluable resource.

**Sharma S. Prabhakar MD MBA FACP FASN**

Texas Tech University Medical Center

control in the context of glomerular disease.

Systemic autoimmune disorders and vasculitides constitute major causes of glomerular disease and often renal failure. The third section deals with such conditions and includes six chapters. Marco Zaffanello provided an excellent overview of the clinical aspects and management of Henoch-Schönlein Purpura in children, while Chi Chiu Mok reviewed the glomerular involvement in systemic lupus erythematosis in an elaborate manner. There are two other chapters covering other autoimmune conditions leading to glomerular disease, namely anti-glomerular basement membrane disease with a detailed description of the clinical features and management (Kouichi Hirayama et al.) and autoimmune glomerulonephritis with special focus on mixed bone marrow chimerism in the treatment (Emiko Takeuchi). Two other chapters discuss pulmonary renal syndrome, with Martin Kimmel et al. discussing the differential diagnosis of the condition in a chapter, while Mitra Naseri describes in the chapter, the rapidly progressive glomerulonephritis specifically leading to pulmonary renal syndrome.

The fourth section includes four chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The first of these is diabetic glomerulopathy, which is the leading cause of renal failure resulting in end stage renal disease in the western hemisphere. This chapter is a very comprehensive review of pathogenesis and clinical features, besides being an exhaustive review of the currently available and emerging therapeutic options. Hequn Zou et al. wrote an excellent review on the glomerular involvement in a related disorder, the metabolic syndrome, a condition that is regarded by many as a distinct disease and is on the rapid rise to epidemic proportions. Daniel Fischman et al. authored a chapter on glomerular disease in cystic fibrosis, a systemic metabolic condition, while in another chapter, Han-Seung Yoon et al. reviewed milder forms of Alport syndrome, a hereditary glomerulopathy.

The final section has two chapters which relate to some general aspects of glomerular diseases. Gertruida van Biljon reviewed in a special chapter, glomerular disease leading nephrosis in children in South Africa. Finally, Toshihiko Ishimitsu described in a concise and clear manner the significance of and approaches to blood pressure control in the context of glomerular disease.

XII Preface

the renal and non-renal sequelae of S pyogenes infections by Luiza Guilherme et al., while W. Michael McShan et al. provided a focused overview on the genomics of post streptococcal glomerulonephritis. The atypical clinical features of poststreptococcal glomerulonephritis are discussed in a chapter written by Toru Watanabe. Finally, there are two chapters that provide recent insights into glomerular complications of

Systemic autoimmune disorders and vasculitides constitute major causes of glomerular disease and often renal failure. The third section deals with such conditions and includes six chapters. Marco Zaffanello provided an excellent overview of the clinical aspects and management of Henoch-Schönlein Purpura in children, while Chi Chiu Mok reviewed the glomerular involvement in systemic lupus erythematosis in an elaborate manner. There are two other chapters covering other autoimmune conditions leading to glomerular disease, namely anti-glomerular basement membrane disease with a detailed description of the clinical features and management (Kouichi Hirayama et al.) and autoimmune glomerulonephritis with special focus on mixed bone marrow chimerism in the treatment (Emiko Takeuchi). Two other chapters discuss pulmonary renal syndrome, with Martin Kimmel et al. discussing the differential diagnosis of the condition in a chapter, while Mitra Naseri describes in the chapter, the rapidly progressive glomerulonephritis specifically

The fourth section includes four chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The first of these is diabetic glomerulopathy, which is the leading cause of renal failure resulting in end stage renal disease in the western hemisphere. This chapter is a very comprehensive review of pathogenesis and clinical features, besides being an exhaustive review of the currently available and emerging therapeutic options. Hequn Zou et al. wrote an excellent review on the glomerular involvement in a related disorder, the metabolic syndrome, a condition that is regarded by many as a distinct disease and is on the rapid rise to epidemic proportions. Daniel Fischman et al. authored a chapter on glomerular disease in cystic fibrosis, a systemic metabolic condition, while in another chapter, Han-Seung Yoon et al. reviewed milder forms of Alport syndrome, a hereditary

The final section has two chapters which relate to some general aspects of glomerular diseases. Gertruida van Biljon reviewed in a special chapter, glomerular disease leading nephrosis in children in South Africa. Finally, Toshihiko Ishimitsu described

Hepatitis C and HIV infections respectively.

leading to pulmonary renal syndrome.

glomerulopathy.

In summary, *An Update on Glomerulopathies - Clinical and Treatment Aspects* is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. While by no means this book replaces currently available textbooks in nephrology, it is the expectation of the Editor that it will form an excellent reference tool for practicing and academic nephrology community. The Editor expresses deep and sincere gratitude to all the authors for their valuable contributions which facilitated the prompt compilation of this invaluable resource.

#### **Sharma S. Prabhakar MD MBA FACP FASN**

Texas Tech University Medical Center USA

**Part 1** 

**Primary Glomerulopathies** 

## **Part 1**

**Primary Glomerulopathies** 

**1** 

*USA* 

**Membranous Nephropathy** 

Abdelaziz Elsanjak and Sharma S. Prabhakar

 *Department of Medicine, Texas Tech University Health Sciences Center* 

Membranous nephropathy (MN), a very common cause of nephrotic syndrome, is a glomerulopathy defined histopathologically by the presence of immune complexes on the extracapillary side of the glomerular basement membrane (GBM). Idiopathic membranous nephropathy (IMN) is an antibody-mediated glomerular disease with no defined etiology, histologically characterized by uniform thickening of glomerular basement membrane (GBM), caused by subepithelial immune complex deposits. Most cases of MN are idiopathic, for instance approximately 75% of the cases of MN in developed countries are idiopathic, or primary membranous nephropathy (IMN). MN can be secondary to a wide spectrum of infections, tumors, autoimmune diseases or exposure to drugs or toxic agents. Examples include systemic lupus erythematosus, hepatitis B antigenemia or other chronic infections, and historically graft vs. host disease, sickle cell anemia, a number of drugs and toxins such

Idiopathic MN is a glomerulus-specific autoimmune disease and second only to focal glomerulosclerosis, is a leading primary cause of the nephrotic syndrome in adults. The name, '*membranous* nephropathy' reflects the pathological observation in light microscopy of thickening in the GBM between and around immune deposits that occur beneath the podocyte foot processes. The histological hallmarks of the disease were first described by Jones and Mellors and Ortega' over 60 years ago. These include "spikes," stained by methenamine silver, of normal GBM that extend between the immune deposits, a fine granular distribution of immunoglobulin (lg) G and the complement component C3 in a capillary-loop pattern revealed by immunofluorescence, and the presence of electron-dense subepithelial immune deposits indicated by electron microscopy (EM). Idiopathic MN most commonly occurs in patients between the ages of 30 and 60 years, with men twice as likely to be affected as women. However, MN does occur in children as well as in the very elderly. Up to 70% of patients present with the nephrotic syndrome and the others garner clinical attention due to abnormalities in urine sediment such as proteinuria. Microscopic hematuria is observed in up to 50% of cases although red cell casts are rare. Hypertension and impaired renal function are uncommon at the outset of the disease and are more likely to

Idiopathic membranous nephropathy (IMN) is an antibody-mediated glomerular disease that is histologically characterized by uniform thickening of glomerular basement membrane (GBM), caused by subepithelial immune complex deposits. The immune

as therapeutic gold salts, penicillamine, tumors, and agents containing mercury

**1. Introduction** 

occur with disease progression

**2. Pathogenesis** 
