New Developments in CKD-MBD. Why is phosphate overload harmful?

Phosphate restriction has been shown to improve clinical outcomes in patients with chronic kidney disease (CKD) . However, the molecular mechanism underlying the harm in phosphate overload remains unclear. Recent studies suggest that the true culprit of phosphate toxicity may not be phosphate per se but calciprotein particles (CPPs) , colloidal nanoparticles composed of calcium phosphate crystals and mineral binding proteins such as Fetuin-A. CPPs are highly bioactive ligands that induce cell damage and innate immune responses. Serum levels of CPPs are increased in CKD patients and independently associated with vascular calcification and chronic inflammation. CPPs may be viewed as a "pathogen" that plays an important role in the pathophysiology of CKD.