ESKD Complications: CKD-MBD

Abstract

In healthy individuals, normal serum concentrations of calcium and phosphorus are maintained through the interaction of three hormones: parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), which is the active metabolite of vitamin D, and fibroblast growth factor 23 (FGF-23). Circulating or soluble klotho also plays a role in mineral homeostasis. These hormones act on four primary target organs: the bone, kidney, intestine, and parathyroid glands. The kidneys play a critical role in the regulation of normal serum calcium and phosphorus concentrations and of the three hormones. Derangements in mineral homeostasis are common and develop early in patients with chronic kidney disease (CKD). By the time patients reach end-stage kidney disease (ESKD), these abnormalities are universally observed. As CKD progresses, the body attempts to maintain normal serum concentrations of calcium and phosphorus by altering the production of calcitriol, PTH, FGF-23, and klotho. Eventually these compensatory responses become unable to maintain normal mineral homeostasis, resulting in (1) altered serum concentrations of calcium, phosphorus, PTH, calcitriol, FGF-23, and klotho, (2) disturbances in bone remodeling and mineralization (often referred to as “renal osteodystrophy”) and/or impaired linear growth in children, and (3) extraskeletal calcification in soft tissues and arteries. In 2006, the term chronic kidney disease–mineral and bone disorder (CKD-MBD) was developed to describe this triad of abnormalities in biochemical measures, skeletal abnormalities, and extraskeletal calcification (Moe et al. Kidney Int. 69(11):1945–1953, 2006). The abnormalities that constitute CKD-MBD are interrelated in both the pathophysiology of the disease and the response to treatment. All the components of CKD-MBD are associated with increased risk of fractures, cardiovascular disease, and mortality in patients with ESKD. To further understand the complex integration of these abnormalities in CKD-MBD, each component will be independently discussed.