General considerations of proximal tubule transport. General considerations of proximal tubule transport. (A) Profile of the tubular fluid to plasma ultrafiltrate ratio (TF/PUF). Selected solutes are shown along the length of the proximal tubule. PUF is a surrogate for the proto-urine in Bowman’s space. Inulin represents a filtered molecule that is neither secreted nor reabsorbed and the rise in its TF/PUF solely reflects reabsorption of water, which concentrates luminal inulin. Sodium reabsorption is near isotonic with water, which results in a very small increase in TF/PUF by the end of the proximal tubule. HCO3− absorption in the early proximal convoluted tubule is particularly avid leading to rapid fall in TF/PUF. The fall in luminal [HCO3−] is accompanied by a reciprocal rise in luminal [Cl−] as reabsorption remains by-and-large isotonic. Inorganic phosphate (Pi) reabsorption is more avid in the earlier parts of the proximal tubule. (B) Generic scheme of the proximal tubule cell. The primary energy currency is organic metabolic substrates that enter the proximal tubule and are catabolized to produce ATP, which serves as the secondary energy currency. Some transporters are directly coupled to ATP hydrolysis (enthalpic transport), such as the H+-ATPase and Na+/K+-ATPase. The latter represents the main workhorse of the proximal tubule responsible for the majority of the cellular ATP consumption. The Na+/K+-ATPase converts the energy stored in ATP into low cellular [Na+] and high cellular [K+]. The presence of K+ conductance allows the [K+] gradient to increase the negative interior potential. The low cell [Na+] and negative voltage serve as the tertiary energy currencies that drive multiple secondary active apical transporters to achieve uphill movement of solutes coupled to downhill movement of Na+ (entropic transport). The transported solutes move in the same (symport or cotransport) or opposite (antiport, exchanger, or countertransport) direction as Na+. Movement of solute can also proceed via paracellular routes driven by electrochemical forces. Norman P. Curthoys, and Orson W. Moe CJASN 2014;9:1627-1638 ©2014 by American Society of Nephrology