INTRODUCTION AND DEFINITION OF CKD–MBD

Chronic kidney disease (CKD) is an international publichealth problem affecting 5–10% of the world population.1Askidney function declines, there is a progressive deteriorationin mineral homeostasis, with a disruption of normal serumand tissue concentrations of phosphorus and calcium, andchanges in circulating levels of hormones. These includeparathyroid hormone (PTH), 25hydroxyvitamin D (25(OH)D),1,25dihydroxyvitamin D (1,25(OH)2D), and other vitaminD metabolites, fibroblast growth factor23 (FGF23), andgrowth hormone. Beginning in CKD stage 3, the ability of thekidneys to appropriately excrete a phosphate load isdiminished, leading to hyperphosphatemia, elevated PTH,and decreased 1,25(OH)2D with associated elevations in thelevels of FGF23. The conversion of 25(OH)D to 1,25(OH)2 Dis impaired, reducing intestinal calcium absorption andincreasing PTH. The kidney fails to respond adequately toPTH, which normally promotes phosphaturia and calciumreabsorption, or to FGF23, which also enhances phosphateexcretion. In addition, there is evidence at the tissue level of adownregulation of vitamin D receptor and of resistance tothe actions of PTH. Therapy is generally focused oncorrecting biochemical and hormonal abnormalities in aneffort to limit their consequences.

The mineral and endocrine functions disrupted in CKDare critically important in the regulation of both initial boneformation during growth (bone modeling) and bonestructure and function during adulthood (bone remodeling).As a result, bone abnormalities are found almost universallyin patients with CKD requiring dialysis (stage 5D), and in themajority of patients with CKD stages 3–5. More recently,there has been an increasing concern of extraskeletalcalcification that may result from the deranged mineral andbone metabolism of CKD and from the therapies used tocorrect these abnormalities.

Numerous cohort studies have shown associations betweendisorders of mineral metabolism and fractures, cardiovasculardisease, and mortality (see Chapter 3). These observationalstudies have broadened the focus of CKD related mineral andbone disorders (MBDs) to include cardiovascular disease(which is the leading cause of death in patients at all stages ofCKD). All three of these processes (abnormal mineralmetabolism, abnormal bone, and extraskeletal calcification)are closely interrelated and together make a major contributionto the morbidity and mortality of patients with CKD.
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