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

Abstract

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 (FE(Na)) and potassium (FE(K)) 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 <approximately 28 weeks GA exceeded intake, leading to a state of negative sodium balance, most infants >/=28 weeks and all infants >approximately 32 weeks GA achieved a state of positive balance, a maturational process associated with a decrease in FE(Na )and increase in ENaC. Infants >approximately 30 weeks GA maintained a state of positive potassium balance. We noted a twofold reduction in FE(K )after approximately 26 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 FE(Na )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.

Postnatal expression of transport proteins involved in acid?base transport in mouse kidney

“…No staining for pendrin was visible in the IMCD (D) or OMCD. Original magnifications ×400-600 secretion increased together with mRNA or protein levels of ROMK or maxi-K channels [10,51].…”

“…After birth the kidney is not completely matured and excretory and reabsorptive functions are not fully developed as evident from animal models as well as from clinical measurements in newborns and infants [6,10,11,28,51]. In human newborns, small infants and in animal models (with the exception of rabbits) it was noted that plasma HCO 3 − levels and the renal threshold for HCO 3 − are lower [11,38] and that the renal capacity to excrete protons and acid-equivalents is only acquired at a later stage of development [6,7,28].…”

Potassium transport in the maturing kidney

“…Although the density of aldosterone binding sites, receptor affinity, and degree of nuclear binding of hormone receptors appear to be similar in mature and immature rats, clearance studies in fetal and newborn animals demonstrate a relative insensitivity of the immature kidney to aldosterone [5,128,129]. This relative hyporesponsiveness is also demonstrated by the observation that the urinary Na + to K + ratio in the newborn typically exceeds 1, despite the fact that both breast milk and commercially available formulas provide Na + to K + in a ratio of 0.5 to 0.6 [4].…”

Early urinary angiotensinogen excretion in critically ill neonates

“…34 The urinary fractional excretion of electrolytes is high in neonates and even higher in premature neonates, indicating immature renal tubular function. 35,36 The correlation between uAGT and FENa suggests that the increased uAGT level in neonates might be partially due to renal Figure 2. Correlation between urinary angiotensinogen and urinary sodium/potassium ratio or urinary fractional excretion of sodium (FENa), potassium (FEK) or chloride (FECl).…”