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Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice

Daniel Caballero1, Yuwen Li2,3, Jonathan Fetene1

  • 1Department of Medicine, Section Endocrinology, Yale University School of Medicine, New Haven, CT, United States of America.

Plos One
|July 14, 2017
PubMed

Insights

Pyrophosphate (PPi) protects against kidney calcification in Npt2a-/- mice. Increasing urinary PPi levels may offer a novel strategy for preventing nephrocalcinosis and kidney stones in phosphaturic disorders.

Area of Science:

  • Nephrology
  • Mineral Metabolism
  • Molecular Biology

Background:

  • Mutations in phosphate transporters NPT2a and NPT2c are linked to kidney stones and nephrocalcinosis.
  • The roles of genetics, diet, and pyrophosphate (PPi) in renal mineral deposit formation are not fully understood.

Purpose of the Study:

  • To investigate the protective role of pyrophosphate (PPi) in a mouse model of renal calcification.
  • To explore PPi as a potential therapeutic target for phosphaturic disorders.

Main Methods:

  • Utilized Npt2a-/- mice to model renal calcifications.
  • Assessed urinary PPi excretion in Npt2a-/- and wild-type (WT) mice.
  • Examined the effect of hypomorphic Extracellular nucleotide pyrophosphatase phosphodiesterase 1 (Enpp1asj/asj) alleles on renal calcification.
  • Administered sodium pyrophosphate intraperitoneally to evaluate its impact on calcification.

Main Results:

  • Npt2a-/- mice exhibited elevated urinary PPi excretion compared to WT mice.
  • Reduced urinary PPi in Npt2a-/- mice with Enpp1asj/asj alleles exacerbated renal calcifications.
  • Intraperitoneal sodium pyrophosphate administration decreased renal calcifications in Npt2a-/- mice.

Conclusions:

  • Urinary pyrophosphate (PPi) acts as a protective factor against renal mineral deposits in Npt2a-/- mice.
  • Modulating urinary PPi levels may represent a novel therapeutic approach for nephrocalcinosis and nephrolithiasis.
  • Further research in humans is warranted to confirm the therapeutic potential of urinary PPi.

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