Elevated Phosphate Levels Induce Markers of Systemic Inflammation and Anemia in Murine Hepatocytes

Abstract

In chronic kidney disease (CKD), elevated serum levels of fibroblast growth factor 23 (FGF23) and phosphate are associated with various pathologies, including systemic inflammation and anemia. Experimental studies have shown that high phosphate can accelerate CKD‐associated pathologies, but direct effects of circulating phosphate on tissues are not well described. Our objective was to compare the effects of phosphate versus FGF23 on primary murine hepatocytes and to determine their respective contributions to systemic inflammation and anemia in the context of CKD. We postulate that in CKD, elevations in serum phosphate levels contribute to systemic inflammation and anemia by directly targeting the liver and inducing gene programs in hepatocytes, which systemically regulate the inflammatory response and iron metabolism. Our study does not only provide novel insights into the basic pathophysiology of CKD, but might also suggest novel therapeutic strategies to block hepatic effects of phosphate in order to tackle CKD‐associated injuries.Support or Funding InformationPROmoTE R25 DK 112731