Twenty-one years of developmental nephrology: the kidney then and now

Abstract.

Developmental renal physiology was guided for a long time by the notion that the "immature" kidney is characterized by glomerular-tubular imbalance, with glomerular preponderance. In accordance with this concept, the filtering capacity of the developing kidney exceeds the ability of the renal tubules to handle the filtrate, resulting in the urinary loss of substances such as amino acids and bicarbonate. Estimates of age-related changes in glomerular volume, based on measurements of glomerular diameter, and of proximal tubular volume, based on measurements of tubular length and tubular diameter, appeared to support this contention. The experimental approach that led to these conclusions was based on the assumptions that the increase in glomerular size is distributed evenly between the vascular and nonvascular elements and that tubular volume increases pari passu with the luminal surface area. Both assumptions were proved wrong. Moreover, micropuncture studies performed in guinea pigs and rats revealed that the proportionality between glomerular filtration and proximal reabsorption of fluid (i.e., glomerulo-tubular balance) is maintained throughout development. Subsequent studies showed that several transport mechanisms function quite adequately from the first days of extrauterine life. Sodium is avidly reabsorbed in distal nephron segments, under the stimulus of the high levels of aldosterone present during infancy. The increase in the secretion of potassium that would occur in the adult under these circumstances is mitigated by the low expression of potassium channels. In the case of phosphate, there is enhanced reabsorption, particularly at the level of the proximal tubule, due in part to a growth-specific NaPi type II transporter. These different adaptive mechanisms converge towards the maintenance of a positive external balance for substances that are essential to growth. The emergence of cellular and molecular biology has also encouraged research in the field of renal morphology. The genes that control mesenchymal-epithelial interactions and the signaling factors that mediate their effect have been described. Progress is being made in the identification of genes involved in certain forms of renal malformations. Novel methods of investigation, such as DNA arrays, are likely to lead to an even fuller, dynamic portrayal of gene expression during nephrogenesis. Characterizing the functional correlates of these genes will require investigators who are not only proficient in molecular biology, but who are also masters of physiological methods.