Phosphate and Phosphate Transporters in Polycystic Kidney Disease
Year: 2026
Type: article
Abstract: Maintenance of inorganic phosphate (Pi) levels within narrow ranges is essential for normal cellular metabolism.Highly regulated renal excretion and less regulated intestinal absorption maintain body Pi balance.When the number of functioning nephrons is reduced in CKD, Pi retention stimulates the production of phosphaturic parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23).PTH and FGF23 inhibit Pi reabsorption in the proximal tubule and increase Pi fractional excretion and intratubular concentration in residual nephrons.When this compensatory mechanism cannot keep up with Pi intestinal absorption, Pi concentration in extracellular fluid increases.While hyperphosphatemia promotes inflammation, oxidative stress, and cardiovascular disease, high Pi concentrations in tubular fluid may be toxic and contribute to CKD progression.Two families of sodium-dependent Pi transporters, NaPi2a, NaPi2b, and NaPi2c, coded by SLC34A1, SLC34A2, and SLC34A3, and PiT1 and PiT2, coded by SLC20A and SLC20B, and the xenotropic and polytropic retrovirus receptor 1 (XPR1), the only cellular Pi exporter, are critical for Pi homeostasis.NaPi2a, NaPi2c, and PiT2 (in renal proximal tubules) and NaPi2b (in small intestine and Henle's loops), under the control of PTH, FGF23, and other factors, balance intestinal absorption and renal excretion, and maintain the extracellular Pi concentration within a narrow range (0.7-1.6 mM in adults).PTH and FGF23 promote endocytosis and degradation of NaPi2a and NaPi2c; FGF23 also downregulates their transcription.In all cells, intracellular Pi concentration, approximately 5 mM, is maintained by NaPi2b and PiT1-mediated Pi entry and by XPR1 mediated export, and by rates of Pi incorporation into and release from organic compounds.Acute Pi loading in rodents and humans induces elevations of PTH and FGF23 within minutes, massive phosphaturia, intratubular precipitation of calcium Pi, and kidney injury.Susceptibility to Pi nephrotoxicity varies among
Source: Kidney360
Institution: Mayo Clinic
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: American Society of Nephrology
OpenAlex ID: W7171813632