The proximal tubule phenotype and its disruption in acute renal failure and polycystic kidney disease.

In light of recent developments in the fields of genetics, molecular, cell and developmental biology, the kidney is receiving increasing attention as a model system for organ development and human diseases. Gene disruption experiments have provided evidence for the essential role of a number of proteins in the earliest phase of nephron development, but very little is known about the identity of such proteins in more advanced stages. This minireview will focus on the proximal tubule and its role in the pathology of ischemic acute renal failure and polycystic kidney disease. Like all other nephron segments, the proximal tubule develops from the metanephrogenic mesenchyme. So far the only genetic model which affects the function of the proximal tubule is a strain of knockout mice with an inactivation of the HNF1 gene. After ischemic renal damage the proximal tubule responds with a different genetic program than the distal tubule. Evidence from human polycystic kidney disease and several animal models of polycystic kidney disease suggests that proximal tubules are affected differently by polycystic kidney disease than distal tubules and collecting ducts.