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

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.