Sodium and potassium clearances by the maturing kidney: clinical-molecular correlates

A temporal dissociation exists between the early appearance of sodium absorptive and later detection of potassium secretory processes in the maturing rabbit collecting duct. To extend the latter findings to the human, we sought to correlate developmental changes in renal sodium and potassium clearances with the molecular expression of corresponding ion channels in kidneys of premature infants. In a longitudinal prospective study of 23- to 31-week gestational age (GA) infants, sodium, potassium, and creatinine clearances were measured weekly for 5 weeks and the absolute and fractional excretions of sodium (FENa) and potassium (FEK) calculated. Gene-specific probes were used to assess steady-state abundance of mRNA encoding the sodium channel ENaC and potassium channel ROMK in homogenates of human kidneys (obtained from the Anatomic Gift Foundation). Although urinary losses of sodium in infants <similar to28 weeks GA exceeded intake, leading to a state of negative sodium balance, most infants greater than or equal to28 weeks and all infants >similar to32 weeks GA achieved a state of positive balance, a maturational process associated with a decrease in FENa and increase in ENaC. Infants >similar to30 weeks GA maintained a state of positive potassium balance. We noted a twofold reduction in FEK after similar to26 weeks GA and no change in ROMK abundance during the developmental window studied. We speculate that the developmental regulation of renal ENaC expression contributes, at least in part, to the decrease in FENa observed with advancing GA, and that in the human, as in the rabbit, there is a delay between the maturation of sodium absorptive and potassium secretory pathways.