Hereditary disorders of renal phosphate wasting - PubMed (original) (raw)

Review

Hereditary disorders of renal phosphate wasting

Amir S Alizadeh Naderi et al. Nat Rev Nephrol. 2010 Nov.

Abstract

Inherited diseases of renal phosphate handling lead to urinary phosphate wasting and depletion of total body phosphorus stores. Clinical sequelae of inherited disorders that are associated with increased urinary phosphate excretion are deleterious and can lead to abnormal skeletal growth and deformities. This Review describes hereditary disorders of renal phosphate wasting taking into account developments in our understanding of renal phosphate handling from the last decade. The cloning of genes involved in these disorders and further studies on their pathophysiological mechanisms have given important insights in to how phosphatonins, such as FGF-23, regulate renal phosphate reabsorption in health and disease. X-linked dominant hypophosphatemic rickets results from mutation of a metalloprotease (PHEX) that has an unidentified role in FGF-23 degradation. Mutation of an RXXR proteolytic cleavage site in FGF-23 prevents degradation and increases circulating levels of FGF-23 in autosomal dominant hypophosphatemic rickets. FGF-23 acts to remove sodium phosphate co-transporters from the luminal membrane of proximal tubular cells with resultant renal phosphate wasting. Loss of function mutations in genes encoding the transporters NaPi-IIc and NaPi-IIa also result in renal phosphate wasting and rickets.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Biol Chem. 1993 Jun 15;268(17):12624-30 - PubMed
    1. Am J Nephrol. 2007;27(5):503-15 - PubMed
    1. Am J Hum Genet. 2006 Feb;78(2):193-201 - PubMed
    1. J Bone Miner Res. 2001 May;16(5):806-13 - PubMed
    1. Am J Physiol Renal Physiol. 2007 Nov;293(5):F1577-83 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources