Elsevier

Seminars in Nephrology

Volume 34, Issue 6, November 2014, Pages 598-611
Seminars in Nephrology

News on Biomarkers in CKD‐MBD

https://doi.org/10.1016/j.semnephrol.2014.09.006Get rights and content

Summary

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.

Section snippets

Parathyroid Hormone

Parathyroid hormone (PTH), the most accredited marker of secondary hyperparathyroidism, is a single-chain, 84–amino acid protein, physiologically produced by parathyroid chief cells in response to fluctuations of plasma concentrations of ionized calcium. Two identified G-protein–coupled receptors, expressed in tissues not necessarily involved with mineral metabolism, and that are sensitive to the N-term region of PTH, are responsible for its biologic effects.6 Circulating PTH includes not only

Noncollagenous Bone Proteins

Besides collagen, bone matrix includes a variety of proteins produced mostly by bone cells, whose functions can be highly specific and, for some of them, still incompletely understood. According to some characteristics, it is possible to tentatively group them into some categories, as shown in Table 1. Notably, some of these proteins now are considered bone hormones and are the subject of intense clinical investigation. Others have intriguing experimental evidence pointing to a potential role

Conclusions

With the new discoveries in bone physiology, the active role of bone disease in the appearance of CKD-MBD becomes more evident. The biochemical markers of mineral metabolism used to date require a complete re-evaluation to take into account the complexity of their metabolism, which generates parent compounds that affect their diagnostic value. Moreover, the endocrine role of bone in the field of mineral and energy metabolism awaits further developments. As a whole, we should regard the

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