Polycystic kidney disease (PKD) is characterized by the presence of fluid-filled cysts in the kidneys. It is the fourth most common cause of chronic renal insufficiency or end-stage kidney disease. This book focuses on the basic and clinical aspects of the burgeoning PKD research under three sections. Section 1 provides a comprehensive guide to the diagnosis, management and treatment of PKD. Section 2 covers most of the fundamental molecular and cellular mechanisms underlying PKD, and how this knowledge is contributing to the development of potential novel therapeutic agents. Finally, section 3 focuses on extra-renal or secondary complications of PKD.

Contents

• Foreword
  Jared J. Grantham.
• Preface
  Xiaogang Li.
• Contributors
• Section I. Diagnosis, Management and Treatment
  • 1. Differential Diagnosis of Autosomal Dominant Polycystic Kidney Disease
    Mariana Alves, Teresa Fonseca, and Edgar A. F. de Almeida.
    • Introduction
    • Autosomal dominant polycystic kidney disease
    • Diagnosis of ADPKD
    • Direct molecular genetic tests for diagnosis
    • Which diagnosis should doctors consider when the patient has multiple renal cysts?
    • Conclusion
    • Conflict of interest
    • References
  • 2. Childhood Polycystic Kidney Disease
    Ameya Patil, William E. Sweeney, Jr., Ellis D. Avner, and Cynthia Pan.
    • Introduction
    • Autosomal recessive polycystic kidney disease (ARPKD)
    • Autosomal dominant polycystic kidney disease (ADPKD)
    • Pathophysiology of cyst formation in childhood PKD
    • The cystic phenotype and targeted future therapy
    • Conclusion
    • Conflict of interest
    • Acknowledgements
    • References
  • 3. Treatment and Management of Autosomal Dominant Polycystic Kidney Disease
    Imed Helal.
    • Introduction
    • Management of kidney disease progression in ADPKD
    • Hypertension management in ADPKD
    • Extrarenal complications management
    • Lifestyle modifications, consultations and long-term monitoring in ADPKD
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 4. Diagnosis and Treatment Modalities of Symptomatic Polycystic Kidney Disease
    Sanem Guler, Sertac Cimen, Scott Hurton, and Michele Molinari.
    • Introduction
    • Genetic mutations and molecular abnormalities
    • Diagnosis of PKD
    • Natural history of ADPKD
    • Symptoms of ADPKD
    • Therapy of ADPKD and management of symptomatic polycystic kidneys
    • Infections
    • Conclusion and perspective
    • Conflict of interest
    • References
  • 5. Blood Pressure Control for Polycystic Kidney Disease
    Rudolf P. Wüthrich, Andreas D. Kistler, Daniel Rodriguez, Sarika Kapoor, and Changlin Mei.
    • Introduction
    • Arterial hypertension in ADPKD
    • Treatment of hypertension in ADPKD
    • Conclusions for clinical practice
    • Conflict of interest
    • References
  • 6. Clinical Trials in Autosomal Dominant Polycystic Kidney Disease
    Alan S.L. Yu, Mireille El-Ters, and Franz T. Winklhofer.
    • Introduction
    • Challenges in drug development and the design of clinical trials in ADPKD
    • Ongoing or recently completed clinical trials of therapy
    • Future directions
    • Conflict of interest
    • Acknowledgement
    • References
• Section II. Molecular Mechanisms
  • 7. Polycystins and Molecular Basis of Autosomal Dominant Polycystic Kidney Disease
    Frederico Moraes Ferreira, Elieser Hitoshi Watanabe, and Luiz Fernando Onuchic.
    • Introduction
    • The PKD1 and PKD2 genes and products
    • PC1-PC2 interactions and assembly
    • Polycystins in the cellular environment and the primary apical cilium
    • Mechanisms of cyst formation and growth in ADPKD
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 8. The Role of Calcium and Cyclic AMP in PKD
    James P. Calvet.
    • Introduction
    • A brief history of cAMP in cystic disease
    • High cAMP levels are associated with PKD
    • What is the cause of the high cAMP?
    • Why high cAMP alone is not the main disease culprit?
    • What is the primary abnormality?
    • What causes the phenotypic switch? An hypothesis
    • Conclusions
    • Conflict of interest
    • Acknowledgements
    • References
  • 9. Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment
    Julie Xia Zhou and Xiaogang Li.
    • Introduction
    • Apoptosis
    • Apoptosis in polycystic kidney disease
    • The role of apoptosis in ADPKD
    • Therapeutic strategies of regulating apoptosis in PKD
    • Conclusion and Perspectives
    • Conflict of interest
    • Acknowledgments
    • References
  • 10. c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease
    Marie Trudel.
    • Introduction
    • Insights into Myc biology
    • Role of c-myc in kidney development and homeostasis
    • Upregulation of c-myc in human ADPKD
    • c-Myc, a key cystogenic factor in murine PKD
    • Conclusion
    • Future directions
    • Conflict of Interest
    • Acknowledgements
    • References
  • 11. The Role of G-protein Coupled Receptor Proteolytic Site (GPS) Cleavage in Polycystin-1 Biogenesis, Trafficking and Function
    Feng Qian.
    • Introduction
    • Polycystin-1 cleavage at the GPS motif via a cis-autoproteolytic mechanism
    • GPS cleavage and polycystin-1 molecular complexity
    • Structural basis of GPS cleavage and subunit association of adhesion GPCRs and the implications for polycystin-1
    • GPS cleavage and polycystin-1 ciliary trafficking
    • Critical and restricted functional role of PC1 cleavage at GPS in vivo
    • Do PC1^Uand PC1^cFLhave different biological functions?
    • GPS cleavage of polycystin-1 and polycystic kidney disease
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 12. Epigenetics in ADPKD: Understanding Mechanisms and Discovering Treatment
    Xiaogang Li.
    • Introduction
    • The epigenome and mechanisms of epigenetic regulation
    • The progression of epigenetic studies in ADPKD
    • Other potential functions of epigenetics in PKD
    • Tools to study epigenetic mechanisms in ADPKD
    • Perspectives and conclusions
    • Conflict of interest
    • Acknowledgements
    • References
  • 13. MicroRNAs and Polycystic Kidney Disease
    Sachin Hajarnis, Ronak Lakhia, and Vishal Patel.
    • Introduction
    • MiRNAs: biogenesis, function and role in kidney development
    • MiRNAs that regulate PKD pathogenesis
    • The potential for a miRNA-based therapeutic approach in PKD
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 14. Role of Inflammation in Polycystic Kidney Disease
    Anil Karihaloo.
    • Introduction
    • Brief clinical description
    • Initiation of cyst formation
    • Inflammation in CKD
    • How might inflammation contribute to disease progression in ADPKD?
    • Mononuclear phagocytes in kidney injury and disease
    • Macrophages accumulate in ADPKD kidneys and promote cyst growth
    • Other infiltrating innate immune cells in PKD
    • Mechanisms regulating immune cell infiltration in PKD
    • Macrophage activation
    • NF-κB and PKD
    • Significance of chronic inflammation in PKD
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 15. Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
    Jong Hoon Park, Yu Mi Woo, Je Yeong Ko, and Do Yeon Kim.
    • Introduction
    • Autosomal dominant polycystic kidney disease (ADPKD)
    • Primary cilia
    • PKD and ciliary defects
    • Conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 16. Implications of Dysfunction of Mechanosensory Cilia in Polycystic Kidney Disease
    Hannah C. Saternos and Wissam A. AbouAlaiwi.
    • Introduction
    • Etiology
    • Clinical manifestations
    • Screening, diagnosis and therapies
    • Primary cilia and polycystic kidney disease
    • Conclusion
    • Conflict of interest
    • Acknowledgements
    • References
• Section III. Extra-renal Manifestations
  • 17. The Liver and Polycystic Kidney Disease
    Mônica Souza de Miranda Henriques and Erick José de Morais Villar.
    • Introduction
    • Autosomal dominant polycystic kidney disease
    • Autosomal recessive polycystic kidney disease
    • Autosomal dominant polycystic liver disease
    • Pathogenesis of hepatic cysts
    • The genetic connection between ADPKD and ADPLD
    • Clinical symptoms
    • Management
    • Conclusions
    • Conflict of Interest
    • Acknowledgement
    • References
  • 18. Seminal Vesicles in Autosomal Dominant Polycystic Kidney Disease
    Jin Ah Kim, Jon D. Blumenfeld, and Martin R. Prince.
    • Introduction
    • Seminal vesicles
    • Anatomic abnormalities of seminal vesicles in ADPKD patients
    • Clinical significance and infertility
    • Summary and conclusion
    • Conflict of interest
    • Acknowledgement
    • References
  • 19. Craniofacial Development and Growth in Polycystic Kidney Disease
    Atsushi Ohazama and Paul T. Sharpe.
    • Introduction
    • The mammalian head
    • Conditional deletion of Pkd1/Pkd2 in mice
    • Mechanical stress and Pkd1/Pkd2 in mastication
    • Mechanical force and head morphology
    • The relationship between Pkd1/Pkd2 and mechanical force on bone formation
    • Mechanical stress-independent Pkd1/Pkd2 function
    • Craniofacial characteristics of ADPKD patients
    • Conclusion and perspective
    • Conflict of interest
    • Acknowledgement
    • References
  • 20. Rapidly Progressive Glomerulonephritis in Autosomal Dominant Polycystic Kidney Disease
    Adey A.A. Hasan, Raafat Makary, and Leighton R. James.
    • Introduction
    • Case
    • Nephrotic syndrome in ADPKD
    • Rapidly progressive glomerulonephritis
    • Proliferative glomerulonephritis in ADPKD
    • Conclusions
    • Conflicts of Interest
    • Acknowledgement
    • References

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