Comprehensive Physiology Wiley Online Library

Renal Handling of Phosphate and Sulfate

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Abstract

In the kidney, both anions, phosphate and sulfate, are almost freely filtered and afterwards reclaimed (reabsorbed) to a large extent from tubular fluid along the proximal tubules. Under normal dietary conditions, fractional excretion of these anions is approximately 10%. Reabsorption of both anions occurs along the proximal tubules by active, saturable, and regulated transepithelial processes. Most of the transporters involved in renal handling of phosphate and sulfate have been identified and their transport functions as well as their cellular localizations have been described in detail. The role of these transporters in the renal handling of phosphate and sulfate has been investigated by the use of several mice knock out models and also by analysis of several inherited human diseases. Numerous hormonal and nonhormonal factors, have been described that alter renal excretion of phosphate or sulfate by mechanisms that alter the abundance of known phosphate/sulfate transporters and consequently renal excretion. These mechanisms contribute to the homeostasis of the extracellular concentrations of phosphate and sulfate. © 2014 American Physiological Society. Compr Physiol 4:771‐792, 2014.

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Figure 1. Figure 1. Model of a proximal tubule cell depicting transport pathways of phosphate across the luminal and basolateral membrane. On the luminal brush border membrane, at least three transporters exist that can mediate sodium‐dependent phosphate transport. The Na+‐dependent uptake of phosphate from primary urine is mediated by NaPi‐lla, NaPi‐llc, and PiT‐2. The relative contribution of these three phosphate transporters may differ among different species. These transporters are energized by the membrane potential and Na+ gradient generated by basolateral Na+/K+‐ATPases. Phosphate exits proximal tubular cells across the basolateral membrane by a yet unknown transport pathway.
Figure 2. Figure 2. Model of a proximal tubule cell (early proximal tubule) depicting transport pathways of sulfate across the luminal and basolateral membrane. On the luminal brush border membrane, at least two transporters exist that can mediate sulfate transport. The Na+‐dependent uptake of sulfate from primary urine is mediated by the NaSi sulfate transporter. This transporter is energized by the membrane potential and Na+ gradient generated by basolateral Na+,K+‐ATPases. Sulfate may also be excreted into primary urine by an anion exchanger, most likely CFEX, that transports sulfate in exchange for oxalate, chloride or bicarbonate. This transport pathway is also linked to Na+‐H+‐exchange mediated mostly by NHE3. Sulfate exits proximal tubular cells across the basolateral membrane in exchange for extracellular anions through the SAT1 anion exchanger. Intracellular bicarbonate is excreted into the basolateral space by the NBCe1 electrogenic Na+‐HCO3 cotransporter. Also this transport process is linked to the NHE3 transporter and carbonic anhydrases generating bicarbonate.


Figure 1. Model of a proximal tubule cell depicting transport pathways of phosphate across the luminal and basolateral membrane. On the luminal brush border membrane, at least three transporters exist that can mediate sodium‐dependent phosphate transport. The Na+‐dependent uptake of phosphate from primary urine is mediated by NaPi‐lla, NaPi‐llc, and PiT‐2. The relative contribution of these three phosphate transporters may differ among different species. These transporters are energized by the membrane potential and Na+ gradient generated by basolateral Na+/K+‐ATPases. Phosphate exits proximal tubular cells across the basolateral membrane by a yet unknown transport pathway.


Figure 2. Model of a proximal tubule cell (early proximal tubule) depicting transport pathways of sulfate across the luminal and basolateral membrane. On the luminal brush border membrane, at least two transporters exist that can mediate sulfate transport. The Na+‐dependent uptake of sulfate from primary urine is mediated by the NaSi sulfate transporter. This transporter is energized by the membrane potential and Na+ gradient generated by basolateral Na+,K+‐ATPases. Sulfate may also be excreted into primary urine by an anion exchanger, most likely CFEX, that transports sulfate in exchange for oxalate, chloride or bicarbonate. This transport pathway is also linked to Na+‐H+‐exchange mediated mostly by NHE3. Sulfate exits proximal tubular cells across the basolateral membrane in exchange for extracellular anions through the SAT1 anion exchanger. Intracellular bicarbonate is excreted into the basolateral space by the NBCe1 electrogenic Na+‐HCO3 cotransporter. Also this transport process is linked to the NHE3 transporter and carbonic anhydrases generating bicarbonate.
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J. Biber, H. Murer, N. Mohebbi, C.A. Wagner. Renal Handling of Phosphate and Sulfate. Compr Physiol 2014, 4: 771-792. doi: 10.1002/cphy.c120031