Mechanisms and Regulation of Intestinal Phosphate Absorption

Abstract

States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH) vitamin D , and dietary phosphate. The molecular mechanisms responsible for the transepithelial transport of phosphate across enterocytes are only partially understood. Indeed, whereas renal reabsorption entirely relies on well-characterized active transport mechanisms of phosphate across the renal proximal epithelia, intestinal absorption proceeds via active and passive mechanisms, with the molecular identity of the passive component still unknown. The active absorption of phosphate depends mostly on the activity and expression of the sodium-dependent phosphate cotransporter NaPi-IIb (SLC34A2), which is highly regulated by many of the factors, mentioned earlier. Physiologically, the contribution of NaPi-IIb to the maintenance of phosphate balance appears to be mostly relevant during periods of low phosphate availability. Therefore, its role in individuals living in industrialized societies with high phosphate intake is probably less relevant. Importantly, small increases in plasma phosphate, even within normal range, associate with higher risk of cardiovascular disease. Therefore, therapeutic approaches to treat hyperphosphatemia, including dietary phosphate restriction and phosphate binders, aim at reducing intestinal absorption. Here we review the current state of research in the field. © 2017 American Physiological Society. Compr Physiol 8:1065-1090, 2018.

Inflammation and Premature Ageing in Chronic Kidney Disease

“…In more detail, P i originating from dietary intake is absorbed by the small intestine by an active transcellular transport or a paracellular pathway [65]. In hypophosphatemia, either normal or increased levels of the active metabolite 1,25(OH) 2 vitamin D 3 are observed in humans [66], and 1,25(OH) 2 vitamin D 3 increases the rate of intestinal P i resorption [67]. Furthermore, the parathyroid glands are affected by elevated serum P i levels and release PTH, which enhances urinary P i excretion by PTH-induced removal of the renal sodium P i cotransporters from the apical membrane [68].…”

Endotoxaemia differentially regulates the expression of renal Ca2+ transport proteins in mice

“…However, urinary Ca 2+ loss seems not to be of relevance in our model as well as in humans with sepsis . Further, the massive drop in food intake in septic mice with a resulting reduction in intestinal Ca 2+ and P i absorption, which favors transcellular absorption via TRPV6 and NaP i ‐2b respectively, could contribute to hypocalcaemia . Indeed, the expression of these important intestinal transporting proteins is decreased in response to LPS, despite an increase in 1,25(OH) 2 D 3 .…”

Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: mutations and disease associations

“…For a more detailed review on the regulation of NaPi-IIb in the intestine the reader is referred to a recent review [33].…”