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ESSENTIALS OF DIAGNOSIS
The Kidney Disease Improving Global Outcomes (KDIGO) work group defined chronic kidney disease mineral bone disorder (CKD-MBD) as a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
Abnormalities of blood levels of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D metabolism.
Abnormalities in bone turnover, mineralization, volume (which together are called renal osteodystrophy), linear growth, or strength.
Vascular or other soft tissue calcification.
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GENERAL CONSIDERATIONS
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The definition of CKD-MBD was developed at an international consensus conference organized by KDIGO and meant to emphasize the importance of disordered mineral metabolism in the pathogenesis of morbidity and mortality on patients with CKD. Although not included in the original discussion, abnormalities in blood levels of fibroblast growth factor 23 (FGF-23) and α-klotho (hereafter called klotho) are considered a component of CKD-MBD. All components of CKD-MBD—abnormalities of blood levels, bone, and extraskeletal calcification—are associated with morbidity and mortality in patients with CKD as discussed throughout this chapter.
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Moe
SM
et al: Chronic kidney disease-mineral-bone disorder: a new paradigm. Adv Chronic Kidney Dis 2007;14:3.
[PubMed: 17200038]
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1. CKD-MBD—Abnormal Blood Levels
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Blood and intracellular levels of calcium and phosphorus are tightly maintained to protect homeostasis and cellular function by an organized series of homeostatic feedback loops that all involve the kidney. In addition, calcium and phosphorus balance is maintained to ensure adequate mineral stores for bone health. The four hormones 1,25(OH)2-vitamin D (hereafter 1,25[OH]2D), PTH, FGF23, and klotho work to regulate homeostasis.
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Vitamin D is taken in through food, supplements, or sunlight, and then synthesized into 25(OH)-vitamin D (25D or calcidiol) at the liver, and to 1,25(OH)2-vitamin D (1,25(OH)2D or calcitriol) by the CYP27B1 (1α-hydroxylase) enzyme in the kidney and other nonrenal sites. CYP27B1 activity is increased by PTH, estrogen, low calcium and decreased by FGF23, calcitriol, and high phosphorus. The major function of 1,25(OH)2D is to enhance intestinal absorption and kidney reabsorption of calcium.
PTH is secreted from the parathyroid gland in response to hypocalcemia and hyperphosphatemia, and is inhibited by 1,25(OH)2D and FGF23. The major target organs of PTH are bone where it increases calcium and phosphorus resorption, and kidney where it increases calcium reabsorption and phosphorus excretion.
FGF23 is synthesized in osteocytes/osteoblasts of bone with the primary effect on kidney to increase phosphorus excretion; FGF23 is stimulated by 1,25(OH)2D, PTH, and likely hyperphosphatemia or increased dietary phosphate.
α-Klotho is synthesized in the kidney where it serves as a coreceptor for FGF23 to enhance phosphaturia and facilitates calcium reabsorption; the extracellular klotho domain is also cleaved and circulates to act on other organs.
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