National Center for Competence in Research NCCR Kidney.CH, Institute of Physiology, University Zurich-Irchel, Zurich, Switzerland.
Compr Physiol. 2018 Jun 18;8(3):1065-1090. doi: 10.1002/cphy.c170024.
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.
低磷血症和高磷血症状态分别会导致佝偻病/骨软化症和肾脏/心血管疾病等有害后果。因此，维持适当的血浆磷酸盐水平是健康的基本要求。这种控制是由肠道和肾脏协同作用执行的，它们吸收磷酸盐的能力受许多激素和代谢因素的调节，其中包括甲状旁腺激素、成纤维细胞生长因子 23、1,25(OH) 维生素 D 和膳食磷酸盐。跨肠细胞转运磷酸盐的分子机制尚未完全阐明。事实上，尽管肾脏重吸收完全依赖于肾脏近端上皮中经过充分特征描述的主动转运机制，但肠道吸收是通过主动和被动机制进行的，被动成分的分子特征仍然未知。磷酸盐的主动吸收主要依赖于钠依赖性磷酸盐共转运体 NaPi-IIb（SLC34A2）的活性和表达，而许多因素，如前面提到的，对其有高度的调节作用。从生理学角度来看，在磷酸盐供应不足的时期，NaPi-IIb 对维持磷酸盐平衡的贡献似乎更为重要。因此，其在生活在高磷酸盐摄入的工业化社会中的个体中的作用可能不太重要。重要的是，即使在正常范围内，血浆磷酸盐的小幅度增加也与心血管疾病风险的增加相关。因此，治疗高磷血症的方法，包括限制饮食中的磷酸盐摄入和使用磷酸盐结合剂，旨在减少肠道吸收。在此，我们综述了该领域的最新研究进展。Compr Physiol 8:1065-1090, 2018.
