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. 2024 Oct;102(10):1217-1227.
doi: 10.1007/s00109-024-02468-y. Epub 2024 Aug 13.

Oral pyrophosphate protects Abcc6-/- mice against vascular calcification induced by chronic kidney disease

Elise Bouderlique  1   2 , Jennifer Kervadec  1   2 , Ellie Tang  1   2 , Jeremy Zaworski  1   2 , Amélie Coudert  3 , Isabelle Rubera  4 , Christophe Duranton  4 , Edmat Khan  1   2 , Jean-Philippe Haymann  1   2   5 , Georges Leftheriotis  4   6 , Michel Daudon  1   2   5 , Emmanuel Letavernier  7   8   9   10
Affiliations

Oral pyrophosphate protects Abcc6-/- mice against vascular calcification induced by chronic kidney disease

Elise Bouderlique et al. J Mol Med (Berl). 2024 Oct.

Abstract

One of the hallmarks of chronic kidney disease (CKD) is the development of vascular calcification. Inorganic pyrophosphate is a potent inhibitor of calcification, and previous studies have reported low plasma pyrophosphate levels in hemodialysis patients. A long-term mouse model of CKD-accelerated vascular calcification was developed to study pyrophosphate metabolism and to test whether oral pyrophosphate supplementation attenuates the propensity for arterial calcification. CKD was induced by repeated injections of aristolochic acid in wild-type and Abcc6-/- mice, which tend to develop vascular calcifications. CKD accelerated the development of vascular calcifications in Abcc6-/- mice, in the aorta and small renal arteries, and decreased circulating pyrophosphate levels. Oral pyrophosphate supplementation for 6 months attenuated CKD-induced vascular calcification in this model. These results show that oral pyrophosphate may be of interest in preventing vascular calcification in patients with CKD. KEY MESSAGES: Chronic kidney disease accelerates the development of vascular calcification in pyrophosphate-deficient mice. Oral pyrophosphate supplementation for 6 months attenuates chronic kidney disease-induced vascular calcification in a mouse model. Oral pyrophosphate may be of interest in preventing vascular calcification in patients with chronic kidney disease.

Keywords: ABCC6; Alkaline phosphatase (ALP); Arterial calcification; Calcium; Chronic kidney disease (CKD); Phosphate; Pyrophosphate (PPi); TNAP.

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