Molecular regulation of nephron endowment

Abstract

Recent data suggests that the number of nephrons in normal adult human kidneys ranges from ∼300,000 to more than 1 million. There is increasing evidence that reduced nephron number, either inherited or acquired, is associated with the development of essential hypertension, chronic renal failure, renal disease in transitional indigenous populations, and possibly the long-term success of renal allografts. Three processes ultimately govern the number of nephrons formed during the development of the permanent kidney (metanephros): branching of the ureteric duct in the metanephric mesenchyme; condensation of mesenchymal cells at the tips of the ureteric branches; and conversion of the mesenchymal condensates into epithelium. This epithelium then grows and differentiates to form nephrons. In recent years, we have learned a great deal about the molecular regulation of these three central processes and hence the molecular regulation of nephron endowment. Data has come from studies on cell lines, isolated ureteric duct epithelial cells, isolated metanephric mesenchyme, and whole metanephric organ culture, as well as from studies of heterozygous and homozygous null mutant mice. With accurate and precise methods now available for estimating the total number of nephrons in kidneys, more advances in our understanding of the molecular regulation of nephron endowment can be expected in the near future.