The Genetics Of Renal Disease

Genetic approaches have revolutionized our understanding of the fundamental causes of human disease by permitting the identification of specific genes in which variation causes or contributes to susceptibility to, or protection from, disease. More than 2,000 disease genes have been identified in the last 20 years, providing important new insight into the pathophysiology of diseases in every field of medicine. Genetic Diseases of the Kidney offers expert insight into the role of genetic abnormalities in the pathogenesis of abnormal kidney function and kidney disease. Genetic abnormalities are carefully presented within the appropriate physiologic context so that readers will understand not only which genes are linked to which diseases but also which pathways lead from a genetic “disturbance” to the systemic appearance of disease. * Lays the essential foundation of mammalian genetics principles for medical professionals with little or no background in genetics * Analyzes specific renal diseases – both monogenic disorders confined to the kidney and systemic diseases with renal involvement – and explains their genetic causes *World-renowned editors and authors offer expert frameworks for understanding the links between genes and complex clinical disorders (i.e., lupus, diabetes, HIV, and hypertension)

This companion to Brenner and Rector's The Kidney offers a state-of-the-art summary of the most recent advances in renal genetics. Molecular and Genetic Basis for Renal Disease provides the nephrologist with a comprehensive look at modern investigative tools in nephrology research today, and reviews the molecular pathophysiology of the nephron as well as the most common genetic and acquired renal diseases. A comprehensive clinical review of Medelian renal disease is also be included. Detailed review of the molecular anatomy and pathophysiology of the nephron that provides relevant basic science to consider when diagnosing and managing patients with these disorders.

Renal genetic disorders may become apparent at any time in life and recognition of specific renal disorders is important in allowing accurate genetic counselling. Active counselling requires knowledge about the natural history of the disorder, an understanding of the genetic component and mode of inheritance, risk of the disorder in other family members, information about patient attitudes towards family planning and the possibility of pre-natal diagnosis. The Genetics of Renal Disease covers these issues in detail. The book provides a comprehensive account of both the hereditary nephropathies and more generalised disorders which may affect the renal tract. It includes comprehensive guidelines from an international group of authors on renal function and development, choromosomal disorders, dysmorphic syndromes, inherited predisposition to kidney cancer and gene therapy for renal cancer. Specific chapters deal with individual renal tract disorders such as an extensive discussion of Alport's disease, cystic renal diseases, the Bardet-Biedl and Alstrom syndromes. Each section gives a brief description of the clinical and pathological features of a particular disorder, followed by a review of the genetics of the disorder including incidence, inheritance of familial occurrence, genetic linkage and gene assignment, and prenatal diagnosis and carrier detection. Original studies are extensively quoted and are referenced at the end of each section. There are a great many dysmorphic syndromes which involve the urinary tract. These are incorporated within the book. Aimed primarily at clinical and medical geneticists, this book will also appeal to researchers into genetic kidney disease and genetic counsellors as well as nephrologists with an interest in this area.

Genetic disorders have emerged as a prominent cause of morbidity and mor tality among infants and adults. As many as 10% to 20% of hospital admis sions and at least 10% of the mortality in this age group are due to inherited diseases. There are at least two factors that have brought genetic disorders into the forefront of pediatrics. One is a great reduction in childhood mortality due to infections and nutritional deficiency states, and the other is the rapid progress made in the identification of genetic defects. Amniocentesis, chorionic villus sampling, and recombinant DNA technology have already had a tremendous impact on the practice of medicine. This is why the first two chapters of this volume are dedicated to general principles of molecular genetics and to a description of the techniques used to diagnose genetic disorders at the DNA level. The relevance of this new area of science to the study of inherited renal diseases is reflected in the large body of knowledge that has been generated regarding the association between various glomerular nephritides and genetic markers such as the HLA system, and even more impressively in the direct or indirect identification of abnormal genes or gene products in Alport's syn drome, autosomal dominant polycystic kidney disease, and Lowe's syndrome. These discoveries figure prominently in the pages of this book. Yet, the progress we have made has barely scratched the surface of the problem.

I would recommend this slim volume for geneticists with an interest in hereditary kidney diseases who would appreciate well written and referenced, up to date papers on the specific conditions included.' Journal of Medical Genetics

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a highly prevalent hereditary renal disorder in which fluid-filled cysts are appeared in both kidneys. Main causative genes of ADPKD are PKD1 and PKD2, encoding for polycystin-1 (PC1) and polycystin-2 (PC2) respectively. Those proteins are localized on primary cilia and function as mechanosensor in response to the fluid flow, translating mechanistic stimuli into calcium signaling. With mutations either of PKD1 or PKD2, hyper-activated renal tubular epithelial cell proliferation is observed, followed by disrupted calcium homeostasis and aberrant intracellular cyclic AMP (cAMP) accumulation. Increased cell proliferation with fluid secretion leads to the development of thousands of epithelial-lined, fluid-filled cysts in kidneys. It is also accompanied by interstitial inflammation, fibrosis, and finally reaching end-stage renal disease (ESRD). In human ADPKD, the age at which renal failure typically occurs is later in life, however no specific targeted medications are available to cure ADPKD. Recently, potential therapeutic targets or surrogate diagnostic biomarkers for ADPKD are proposed with the advances in the understanding of ADPKD pathogenesis, and some of them were attempted for clinical trials. Herein, we will summarize genetic and epi-genetic molecular mechanisms in ADPKD progression, and overview the currently available biomarkers or potential therapeutic reagents suggested.