Received September 21, 2007
Revised October 2, 2007
Accepted after revision October 2, 2007
Renal calcium stones: Insights from the control of bone mineralisation
Shabbir H Moochhala 1,
John A Sayer 1,
Georgina Carr 1,
Nick L Simmons 1*
1 University of Newcastle upon Tyne
* To whom correspondence should be addressed. E-mail: n.l.simmons{at}ncl.ac.uk.
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Abstract |
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Extracellular pyrophosphate (PPi) plays a central role in the control of normal bone mineralisation since it antagonises inorganic phosphate in the promotion of hydroxyapatite deposition. Studies using knockout mice have established the functional importance of PPi generation via nucleotide pyrophosphatase phosphodiesterases (NPP) and of PPi transmembrane transport by the ANK protein. Tissue non-specific alkaline phosphatase activity counteracts this by hydrolysis of PPi to inorganic phosphate. The molecular nature and transport function of ANK are reviewed. A close parallel is drawn between the controlled mineralisation of bone and the prevention of abnormal calcium crystal deposition within the kidney, especially when concentrated urine is produced. PPi is present in urine and ANK is expressed in the cortical collecting duct where PPi transport to both the tubular lumen and renal interstitium may occur. PPi may also be generated here by nucleoside triphosphate diphosphohydrolases (NTPD2 and 3) together with NPP1. Alkaline phosphatase activity is restricted to the proximal nephron, remote from these sites of PPi generation, transport and function. The physiological importance of PPi generation and transport in preventing idiopathic calcium renal stone disease and nephrocalcinosis now needs to be established.
Key Words:
Calcium, Kidney, Urine
