Renal phosphate handling in human--what can we learn from hereditary hypophosphataemias?

Renal reabsorption of inorganic phosphate is critical for the maintenance of phosphate homeostasis. The sodium dependent phosphate cotransporters NaPi-IIa and NaPi-IIc have been identified to fulfill this task at the brush border membrane of proximal tubule cells. Various factors including dietary phosphate intake, parathyroid hormone, or the so called phosphatonins such as FGF23 have been shown to regulate activity of these transporters.

This review seeks to give an update on our current knowledge about regulatory mechanisms involved in human renal phosphate reabsorption.

Recently, an increasing number of genes have been identified that are directly associated with inherited phosphate wasting disorders (Klotho, PHEX, DMP1 and NHERF1). Several of these genes are predominantly expressed by osteocytes and osteoclasts in the bone suggesting indispensable signalling pathways between kidneys and the skeleton.

In this review, the affected gene products in these inherited hypophosphataemias and their contribution to phosphate homeostasis are discussed.