News on biomarkers in CKD-MBD

The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. Also, we considered their relationship with cardiovascular mortality. Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. Their diagnostic role in clinical practice awaits further studies.