Molecular determinants of sodium and water balance during early human development

The past decade has seen enormous progress in understanding the renal regulation of salt and water homeostasis. Most of the key transporters have been cloned, and their physiological importance has been revealed from studies of children with inherited diseases and from mutagenesis studies on a cellular level. We are beginning to understand the complexity with which the activity of these transporters is regulated by hormones. Studies on experimental animals have uniformly shown that the majority of renal salt and water transporters undergo profound changes in the postnatal period. There is generally a robust increase in the number of transporters expressed in a single tubular cell. Many of the transporters also shift their expression from one isoform to another with a somewhat different function. The short-term regulation of salt and water transporters, the key to a well-functioning homeostatic system, is often blunted in the early postnatal period. Taken together, these findings explain some phenomena well known in infants. The low urinary concentrating capacity can, for example, be at least partially attributed to immaturity of the expression of water channels, sodium losses in preterm infants to low expression of the energy generator for salt transport, Na⁺,K⁺-ATPase, and the disposition to acidosis to immaturity of the Na⁺/H⁺exchanger. We propose that further studies on how these transporters are regulated will lead to the improved prevention and treatment of salt water balance disorders in infants.