Treatment with pyrophosphate inhibits uremic vascular calcification

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Treatment with pyrophosphate inhibits uremic vascular calcification W Charles O'Neill, Koba A. Lomashvili, Hartmut H. Malluche, Marie-Claude Faugere, Bruce L. Riser Kidney International Volume 79, Issue 5, Pages 512-517 (March 2011) DOI: 10.1038/ki.2010.461 Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 1 Change in plasma pyrophosphate (PPi) concentration after injection of PPi containing tracer [32P]PPi. (a) Single subcutaneous injection of 80 μmol/kg sodium PPi in three different rats. (b) Single intraperitoneal injections of 0.026 μmol/kg (solid symbols) or 2.6 μmol/kg (open symbols) sodium PPi in a volume of 5 ml/kg. The increment in plasma PPi concentration was calculated from the specific activity of the injected 32PPi. Kidney International 2011 79, 512-517DOI: (10.1038/ki.2010.461) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 2 Effect of pyrophosphate (PPi) on aortic calcium content in uremic rats. Rats were fed a diet consisting of 2.5% protein, 1.06% phosphorus, 0.92% calcium, and 0.75% adenine for 4 weeks and received sodium PPi in Hank's buffered saline or saline alone by daily intraperitoneal injection of 5 ml/kg. Each point represents a single animal. Kidney International 2011 79, 512-517DOI: (10.1038/ki.2010.461) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 3 Plasma pyrophosphate (PPi) concentration after single intraperitoneal injections of 160 μmol/kg sodium PPi in a volume of 40 ml/kg. Results are means±s.e.m. of four animals. *P<0.01, **P<0.001, #P<0.05 vs baseline. Kidney International 2011 79, 512-517DOI: (10.1038/ki.2010.461) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 4 Effect of peritoneal infusion of pyrophosphate (PPi) on uremic vascular calcification. Rats were fed a diet consisting of 2.5% protein, 1.06% phosphorus, 0.92% calcium, and 0.75% adenine for 4 weeks and given calcitriol 40 ng/kg by subcutaneous injection 3 times per week. PPi was infused daily through a peritoneal catheter in a volume of 40 ml/kg. Each point represents a single animal. *P<0.005 vs control. Kidney International 2011 79, 512-517DOI: (10.1038/ki.2010.461) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 5 Histology of the diaphragm and parietal peritoneum in uremic rats given sodium pyrophosphate (PPi) by intraperitoneal injection. (a) Vehicle; (b) 0.8 mmol/l PPi; (c) and 4 mmol/l PPi. Hematoxylin and eosin staining. Kidney International 2011 79, 512-517DOI: (10.1038/ki.2010.461) Copyright © 2011 International Society of Nephrology Terms and Conditions