The old saying goes “some things never change.” However, the reality is most things change. Some of the changes are subtle in onset, such as global warming, whereas others are more dramatic, such as removing Pluto’s status as a planet. These two examples show how science advances our knowledge and understanding and highlight the importance of periodically reevaluating our definitions. In this issue of Advances in Chronic Kidney Disease, we share the rationale for, and review the components of, the newly defined disorder of CKD-MBD (Chronic Kidney Disease–Mineral Bone Disorder). Kidney Disease: Improving Global Outcomes (KDIGO) recently sponsored a controversies conference that led to this new definition. The conference attendees felt the term renalosteodystrophy should be used exclusively to define alterations in bone morphology associated with CKD and the term CKD–Mineral Bone Disorder (CKD-MBD) should be used to describe the broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism caused by CKD. CKD-MBD is manifested by an abnormality of any one or a combination of the following:laboratory—abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; bone—changes in bone turnover, mineralization, volume, linear growth, or strength; and calcification—vascular or other soft-tissue calcification. The pathogenesis, clinical manifestations, and treatment of these components of CKD-MBD are described in detail in this issue of Advances in Chronic Kidney Disease.
The components of CKD-MBD are not new. What is new is the science behind our understanding of how these components are interlinked from a diagnostic and therapeutic perspective. In the past, the primary objective of treating elevated parathyroid hormone was to attempt to normalize bone turnover and histology. However, we now know that the complexities of bone physiology and pathology are broader than simply changes in turnover. Thus, the new KDIGO classification for renal osteodystrophy evaluates turnover, mineralization, and volume. Although PTH remains the best surrogate marker for turnover, measurement of PTH is fraught with problems. Multiple factors can affect mineralization, including vitamin D status, calcium, phosphorus, and gonadal hormones. Volume will be decreased as part of normal aging, with superimposed losses caused by increased turnover. Given these complexities, the finding that fracture rates are very high in dialysis patients is not surprising. Interestingly, both extremes of PTH appear to lead to increased risk. This narrow window of optimized bone remodeling complicates both the diagnosis and management of CKD-MBD.
In the past 5 years, multiple studies that utilized electron-beam computed tomography (EBCT) have confirmed that coronary-artery calcium is highly prevalent when patients start dialysis and almost uniformly worsens over time on dialysis. Calcification of both intimal and medial layers of peripheral arteries observed by plain radiograph is associated with increased mortality. Most, but not all, studies have identified excess calcium-containing phosphate binders as a risk factor, and prospective studies confirmed these observations. These studies support theneed to more attentively study and understand the calcium burden from medications and its role in vascular calcification. Thus, the management of CKD-MBD is more difficult because of the previously unappreciated risks associated with some therapies.
These advances in scientific understanding of all of the components of CKD-MBD, and their interrelation, warrant this new definition. We hope that this issue of Advances in Chronic Kidney Disease will help the Nephrology community to understand the rationale and the implications of CKD-MBD. Editing this outstanding issue has been our pleasure, and we are grateful to our contributing authors.
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