THE ROLE OF CALCIUM PHOSPHATE MICROCRYSTALS AND CALCIPROTEIN PARTICLES (CPPs) IN CHRONIC KIDNEY DISEASE (CKD) PROGRESSION AND ASSOCIATED INFLAMMATION

Chronic kidney disease (CKD) is a global health burden marked by disturbances in mineral metabolism, inflammation, and tissue injury. Impaired phosphate excretion and calcium dysregulation promote mineral deposition in the kidney and vasculature, linking to inflammatory and fibrotic pathways. Calcium phosphate microcrystals and calciprotein particles (CPPs) form when calcium-phosphate nanophases are stabilized by serum proteins, circulating as CPP‑I or the more active crystalline CPP‑II. Postprandial phosphate surges and bone remodeling favor their formation. CPPs induce endothelial dysfunction, NLRP3 inflammasome activation, oxidative stress, and pro-inflammatory signaling, while phosphate amplifies renal fibrosis through GM‑CSF, MCP-1/CCR2, and Akt/mTORC1 pathways. Clinically, CPPs contribute to vascular calcification, arterial stiffness, and cardiovascular risk. Early interventions, including phosphate binders such as sucroferric oxyhydroxide, reduce CPP activity and inflammation, highlighting the translational potential of targeting CPPs. Understanding the molecular mechanisms of CPP-induced injury remains critical to guide future therapies in CKD.