Clinical Consequences of Mutations in Sodium Phosphate Cotransporters

Abstract

SummaryThree families of sodium phosphate cotransporters have been described. Their specific roles in human health and disease have not been defined. Review of the literature reveals that the type II sodium phosphate cotransporters play a significant role in transepithelial transport in a number of tissues including kidney, intestine, salivary gland, mammary gland, and lung. The type I transporters seem to play a major role in renal urate handling and mutations in these proteins have been implicated in susceptibility to gout. The ubiquitously expressed type III transporters play a lesser role in phosphate homeostasis but contribute to cellular phosphate uptake, mineralization, and inflammation. The recognition of species differences in the expression, regulation, and function of these transport proteins suggests an urgent need to find ways to study them in humans.

Wakame (<i>Undaria pinnatifida </i>) modulates hyperphosphatemia in a rat model of chronic renal failure

“…Hyperphosphatemia has been identified in the past decade as a strong predictor of mortality in patients with advanced CKD (4,27,28). More recent studies have shown that the association between HP concentrations and higher mortality is not restricted to persons with renal disease ; it can also be observed in persons with cardiovascular disease and even in the general population (29).…”

“…Secondary hyperparathyroidism, induced by hyperphosphatemia and 1,25 -(OH)2 vitamin D3 deficiency, is accompanied by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone, which results in renal osteodystrophy (4 -6). These pathologies have established the concept of CKD-mineral and bone disorder (CKD-MBD), which recognizes that CKD leads to higher morbidity and mortality due to cardiovascular disease and poor life prognosis (1,2,4). In response, a treatment strategy that emphasizes life prognosis has been recommended throughout the world.…”

The Role of Sodium-Dependent Phosphate Transporter in Phosphate Homeostasis

“…The NaPi transporter SLC34 is mainly responsible for Pi homeostasis in the body (1,4). Three members of the SLC34 transporter family (SLC34A1-3) have been identified.…”

“…Mutation of NaPI-IIc causes autosomal recessive disorder hereditary hypophosphatemic rickets with hypercalciuria (HHRH) (4,10). Clinical studies suggest that HHRH is a primary renal Pi wasting disorder, resulting in increased serum 1,25-dihydroxyvitamin D3 concentrations with associated intestinal Ca 21 hyperabsorption, hypercalciuria, and rickets/osteomalacia.…”

Homeostasis, the Milieu Intérieur, and the Wisdom of the Nephron

“…Emerging details on phosphate metabolism have identified a family of sodium phosphate transporters that help reabsorb the bulk of the filtered phosphate in the proximal tubule (66). These transporters appear to be affected by a series of factors, including the recently characterized fibroblast growth factor 23 and its obligate coreceptor Klotho, which together, via the fibroblast growth factor receptor, inhibit the reabsorption of sodium-dependent phosphate reabsorption and lower vitamin D levels by downregulating the gene for 1a-hydroxylase (67).…”