Polycystic kidney disease: from bench to bedside

One of the interesting landmarks of a research career is the phase where one is asked to edit a book on a topic that has been the subject of your life’s work. Acceptance of this task is fraught with peril and fond reminiscence of colleagues around the world. The peril comes from the reality that no single book can encompass the worldwide effort that has been brought to bear on understanding the polycystic kidney disease (PKD) entities. This understandably leads to omissions of important work by highly talented researchers. To our colleagues who feel they should have been included with the authors contributing to this book, we offer our apologies. To our readers, whatever excellence you find in this book, that is due to the excellent work of the chapter authors. Whatever deficiencies you note are our responsibility.

The advances made in understanding the molecular cell biology, signaling and pathogenesis of polycystic kidney diseases delineates many of the best attributes of the private/public faith in scientific research. From the early pioneering work of Jared Grantham who worked to bring PKD to the attention of the scientific establishment, to the scientists working in the early days of genomics to identify genes responsible for PKD, the advances have been breathtaking in scope and implications. When the PKD1 gene was first discovered, it was not yet clear that this discovery would have links to work in such diverse organisms such as chlamydomonas, Caenorhabditis elegans, drosophila and in disease entities ranging from congenital birth defects, diabetes, obesity and cancer. A major advancement was the determination that the protein products of the genes responsible for PKD were found in cilia, creating a new class of diseases known as renal ciliopathies.

Aside from autosomal dominant and autosomal recessive forms of PKD, there are a number of other inherited conditions associated with the development of renal cysts and whose gene products are found in cilia, basal bodies and centrioles. Along with the PKDs, these additional conditions can also have liver fibrocystic pathology as well as other organ involvement and include: nephronophthisis, Meckel sycdrome, Bardt–Biedl syndrome and orofacial digital syndrome. This book will review PKD and the protein products of the PKD genes (PKD1/PKD2, polycystins 1 and 2; and PKHD1, fibocystin/polyductin). The other renal ciliopathies will also be reviewed since there is considerable overlap in pathways involved in their renal cystic pathology.

Clinical aspects of PKD include chapters on pain management and PKD-associated hypertension. These chapters address critical complications associated with the inheritance of autosomal dominant PKD. As these conditions involve several organs, there can be complications associated with autosomal dominant PKD. The end of the battle, but not the patient, is renal demise, so there is an excellent review of end-stage disease in autosomal dominant PKD. Ultimately, all of us in the field of PKD research would like to find a treatment for these renal ciliopathy patients. A chapter on the current state of clinical trials and preclinical studies is included; however, these types of studies have mushroomed over the last decade and by the time you read this chapter, there may be additional pathways being targeted and new clinical trials started.

It is our hope that this book, with its ability to be modified, improved, updated and reworked will serve as a template for later editors and researchers. To our colleagues in the field of PKD, we thank them for their efforts and intellectual stimulation as we spend many happy hours reading and contemplating their papers.