Over the past 25 years, identification of the genetic variants causing inherited kidney diseases has tremendously enhanced our understanding of the molecular basis of disease, allowing identifying new therapeutic targets susceptible to alleviate disease onset or progression. At the same time, these genetic discoveries have been a dominant force in the field of renal physiology, providing clues for a number of essential functions that were previously un-known or only postulated on the basis of classical experimental approaches. The clustering of kidney disease in families has long been recognized. The monogenic disorders of the kidney are caused by mutations in genes coding for a large variety of proteins including receptors, channels and transporters, enzymes, transcription factors, and structural components. Since the kidney is a complex organ involving numerous specialized cell types performing highly regulated homeostatic functions, these disorders often affect vital processes including water and electrolyte balance, blood pressure regulation, acid-base homeostasis, hormone and vitamin metabolism, growth and puberty, innate and adaptive immunity, metabolic clearance and secretion of drug metabolites, and central nervous and cognitive functions.

In addition to monogenic renal diseases, there is strong evidence for a genetic (heritable) component to various aspects of renal function ranging from the glomerular filtration rate (GFR) to the tubular handling of ions and the susceptibility to chronic kidney disease (CKD) or hypertension. Classic twin studies demonstrated heritabilities between 40 and 50% for the tubular handling of major ions, and up to 63% for calculated creatinine clearance. The advent of genetic technologies and the rapid increase in the identification of genes causing inherited kidney disorders or associated with complex renal traits provided unprecedented insights into basic principles operating in different nephron segments. In turn, these insights improved our under-standing of important transport mechanisms, their regulation, and their involvement in homeostatic processes, and they provided novel therapeutic targets.

Regards

Calvin Parker

Editorial Assistant

Journal of Nephrology and Urology