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Mineral metabolism and vitamin D in chronic kidney disease—more questions than answers

Nature Reviews Nephrology volume 7, pages 341–346 (2011)Cite this article

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Abstract

Patients with chronic kidney disease (CKD) are at increased risk of total and cardiovascular morbidity and mortality. The underlying pathophysiology of this association remains largely unexplained and there is currently no clear interventional pathway. Emphasis has been placed on measuring serum levels of calcium, phosphate and parathyroid hormone (PTH) to monitor disease progression, driven by the assumption that achieving values within the 'normal' range will translate into improved outcomes. Retrospective studies have provided a body of evidence that abnormal levels of mineral biomarkers, and phosphate in particular, are associated with clinical events. Disturbances in vitamin D metabolism are also likely to contribute to the pathophysiology of CKD. Designing studies that yield useful information has proved to be difficult, partly owing to conceptual and financial limitations, but also because of the tight interdependency of calcium, phosphate and PTH, and the potential impact of vitamin D on these mineral metabolites. An intervention that perturbs any one of these factors is likely to exert effects on the others, making isolation of the individual variables almost impossible. However, some therapies in current use have the potential to act as probes to answer questions relating to the association between mineral biomarkers and outcomes in CKD.

Key Points

  • Patients with chronic kidney disease show exceptionally high rates of total and cardiovascular morbidity and mortality, but much of the underlying pathophysiology remains unexplained

  • Abnormalities in levels of mineral metabolites and regulators, such as calcium, phosphate, parathyroid hormone, fibroblast growth factor 23 and vitamin D, have been linked to the progression of cardiovascular disease and poor outcomes

  • Phosphate has the steepest mortality dose–response relationship; a U-shaped relationship sometimes exists between levels of mineral biomarkers and outcomes, particularly for levels of parathyroid hormone

  • Although vitamin D has major interactions with mineral metabolism, no conclusive evidence exists showing that treatment with vitamin D receptor activators is beneficial for patients with chronic kidney disease

  • Current therapies, such as cinacalcet and phosphate binders, could be used to probe the relationship between various mineral biomarkers as well as to assess their contribution to disease

  • Future trial design should consider the possibility of comparing two or more levels of therapy, which could yield important information about appropriate target ranges

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Renal and Transplantation Department, 6th Floor, Borough Wing, Guy's Hospital, Great Maze Pond, SE1 9RT, London, UK

    David J. A. Goldsmith

  2. Centre for Nephrology, UCL Medical School, Royal Free Campus, Rowland Hill Street, NW3 2PF, London, UK

    John Cunningham

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D. J. A. Goldsmith and J. Cunningham contributed equally to discussion of content for the article, and to writing, editing and reviewing of the manuscript before submission.

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Correspondence to John Cunningham.

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D. J. A. Goldsmith has received honoraria/fees from Amgen, Fresenius, Genzyme, Novartis, and Shire. J. Cunningham has received research support from Abbott and Amgen, and honoraria/fees from Amgen, Cytochroma, Fresenius, Genzyme, Leo Pharma, Novartis, and Shire.

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Goldsmith, D., Cunningham, J. Mineral metabolism and vitamin D in chronic kidney disease—more questions than answers. Nat Rev Nephrol 7, 341–346 (2011). https://doi.org/10.1038/nrneph.2011.53

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