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PLoS One. 2017 Jul 13;12(7):e0180098. doi: 10.1371/journal.pone.0180098. eCollection 2017.

Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice.

Author information

1
Department of Medicine, Section Endocrinology, Yale University School of Medicine, New Haven, CT, United States of America.
2
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America.
3
Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
4
Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America.
5
Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
6
Department of Pathology, Yale University School of Medicine, New Haven, CT, United States of America.

Abstract

Mutations in the proximal tubular sodium-dependent phosphate co-transporters NPT2a and NPT2c have been reported in patients with renal stone disease and nephrocalcinosis, however the relative contribution of genotype, dietary calcium and phosphate, and modifiers of mineralization such as pyrophosphate (PPi) to the formation of renal mineral deposits is unclear. In the present study, we used Npt2a-/- mice to model the renal calcifications observed in these disorders. We observed elevated urinary excretion of PPi in Npt2a-/- mice when compared to WT mice. Presence of two hypomorphic Extracellular nucleotide pyrophosphatase phosphodiesterase 1 (Enpp1asj/asj) alleles decreased urine PPi and worsened renal calcifications in Npt2a-/- mice. These studies suggest that PPi is a thus far unrecognized factor protecting Npt2a-/- mice from the development of renal mineral deposits. Consistent with this conclusion, we next showed that renal calcifications in these mice can be reduced by intraperitoneal administration of sodium pyrophosphate. If confirmed in humans, urine PPi could therefore be of interest for developing new strategies to prevent the nephrocalcinosis and nephrolithiasis seen in phosphaturic disorders.

PMID:
28704395
PMCID:
PMC5509111
DOI:
10.1371/journal.pone.0180098
[Indexed for MEDLINE]
Free PMC Article

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