Genetics Of Kidney Diseases

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.

Organogenesis of the kidney has been intensely studied for over a century. In recent years advances in molecular techniques have not only made great inroads into exploring the genetic regulation of this complex process but also began to unravel the molecular basis of many forms of congenital kidney disease. This book is a comprehensive study on these findings and the only book available with such in depth coverage of the kidney. Hundreds of color figures depicting key events in all aspects of kidney development Full coverage of the genetic and cellular basis of kidney development Analysis of the genetic basis of the major congenital kidney diseases

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.

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