Intestinal phosphate transport: a therapeutic target in chronic kidney disease and beyond?
Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD), contributing to the increased cardiovascular morbidity and mortality seen in this patient group. Results from retrospective studies suggest that small increases in serum phosphate concentration, within the normal or near-normal range, also correlate with increased cardiovascular morbidity and mortality and have led to the suggestion that detection and preventative treatment of positive phosphate balance is important in healthy individuals as well as in those with CKD. Phosphate homeostasis is maintained by the crosstalk between intestinal phosphate absorption and renal phosphate excretion; however, relatively little is known about the mechanisms of intestinal phosphate transport. Our current understanding is that the intestinal type II sodium phosphate cotransporter, NaPi-IIb, plays a significant role in absorption. It may also be involved in the sensing of dietary phosphate composition and the release of hormonal factors that modulate renal phosphate reabsorption to achieve phosphate balance. Interestingly, studies using NaPi-IIb knockout mice with adenine-induced CKD show only partial attenuation of hyperphosphatemia, suggesting that an additional sodium-independent pathway is involved in phosphate absorption. The aim of this review is to discuss our current knowledge of the processes and role of the intestine in phosphate homeostasis and to provide evidence that this organ could be targeted for the treatment of hypophosphatemia and hyperphosphatemia.
London Epithelial Group, UCL Centre for Nephrology, London, UK.
Grace J
GJ
Lee
Joanne
J
Marks
D006706:Homeostasis; D006801:Humans; D054559:Hyperphosphatemia / Q000188:drug therapy / Q000209:etiology; D017674:Hypophosphatemia / Q000188:drug therapy / Q000209:etiology; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D012189:Retrospective Studies
D010710:Phosphates