Acid-base regulation in the renal proximal tubules: Using novel pH sensors to maintain homeostasis

The kidneys play a critical role in precisely regulating the composition of the plasma to maintain homeostasis. To achieve this, the kidneys must be able to accurately determine or “sense” the concentration of a wide variety of substances and to make adjustments accordingly. Kidneys face a key challenge in the arena of pH balance, as there is a particularly narrow range over which plasma pH varies in a healthy subject (7.35–7.45) and this pH must constantly be protected against a variety of onslaughts (changes in diet, activity, and even elevation). The proximal tubule, the first segment to come into contact with the forming urine, plays an important role in helping the kidneys to maintain pH homeostasis. Recent studies have identified a number of novel proximal tubule proteins and signaling pathways that work to sense changes in pH and subsequently modulate renal pH regulation. In this review, we will highlight the role of novel players in acid-base homeostasis in the proximal tubule.