Molecular Pathogenesis of Diseases of the Kidney

The ability to define the pathological basis of kidney diseases has advanced substantially since the completion of the Human Genome Project. Moreover, advances in technology have been greater in the past decade than has ever been seen in modern medicine. These advances combine to open the door to a richer understanding of both normal and pathological processes involved in kidney function and consequent diseases. Kidney disease is defined as either decreased ability to filter products of metabolism (such as creatinine) or the loss of protein in the urine (proteinuria). The ability of the kidney to filter metabolic substances into the urine is referred to as the glomerular filtration rate (GFR). With worsening proteinuria or deterioration in GFR, there is a greater risk of end-stage kidney disease (ESKD) requiring dialysis or transplantation, as well as increased risk of cardiovascular disease. The molecular pathogenesis of kidney diseases with Mendelian modes of inheritance are most well understood. Three such entities will be reviewed including focal segmental glomerulosclerosis (FSGS), Fabry disease, and polycystic kidney diseases. Additionally, Bartter’s and Gitelman’s diseases will be discussed as examples of renal tubular disorders, which can result in electrolyte and acid/base disturbances. First, we give a brief description of the structure and important physiologic mechanisms in the normal functioning kidney.