Ontogeny of proximal tubule acidification

The proximal tubule is responsible for the reabsorption of 80% of the filtered load of bicarbonate in adults. Proximal tubule bicarbonate reabsorption is affected by a number of hormones, acid-base balance, and the extracellular fluid volume status [1]. The adult proximal tubule thus plays a central role in acid-base homeostasis. The mechanisms and regulation of proximal tubule acidification have been well characterized at the whole animal and tubular level [1]. Recent advances in cellular and molecular biology have provided further insights. However, while the neonatal proximal tubule likely also plays a critical role in acid-base homeostasis, relatively little is known about the immature segment.The normal serum bicarbonate concentration in human infants in the first year of life averages 22 mEq/liter, and is significantly lower than that measured in adults [2]. The difference from the adult value is even more pronounced if one compares premature humans whose normal serum bicarbonate concentration averages 19 mEq/liter and where normal values can be as low as 14.5 mEq/liter [3]. The lower serum bicarbonate level in neonates and infants is due to a lower threshold for bicarbonate [2]. There are a number of potential reasons for the lower threshold for bicarbonate in neonate infants. The extracellular volume is comparatively expanded in neonates and the serum albumin is lower [4]. These variables can affect the peritubular oncotic and hydrostatic pressure to decrease net proximal tubular solute reabsorption [5–8]. There are developmental changes in diet, absorption and metabolism which may affect acid-base balance. In addition, the hormonal milieu which affects renal reabsorption of bicarbonate is significantly different in neonates [9–12]. Finally, since most of filtered bicarbonate is reabsorbed by the proximal tubule, tubular immaturity may be a significant factor to explain the maturational changes in the bicarbonate threshold. This review discusses what is currently known about the mechanism of neonatal proximal tubule acidification and the factors which may play a role in the maturation of this segment