Chronic kidney disease–mineral and bone disorder

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

Abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism

Abnormalities in bone turnover, mineralization, volume, linear growth, or strength

Vascular or other soft-tissue calcification

CKD–MBD explains, at least in part, the high morbidity and mortality of CKD patients, linking kidney and bone disease with cardiovascular complications. It is a matter of discussion whether CKD–MBD may be considered a real syndrome or not.

CKD–MBD broadens the "old" concept of "renal osteodystrophy", which now should be restricted to describing the bone pathology associated with CKD. Thus, renal osteodystrophy is currently considered one measure of the skeletal component of the systemic disorder of CKD–MBD that is quantifiable by histomorphometry of bone biopsy. New guidelines have been recently released.

Pathophysiology

It is well known that as kidney function declines, there is a progressive deterioration in mineral homeostasis, with a disruption of normal serum and tissue concentrations of phosphorus and calcium, and changes in circulating levels of hormones. These include parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) vitamin D; calcidiol), 1,25-dihydroxyvitamin D (1,25(OH)2 vitamin D; calcitriol), and other vitamin D metabolites, fibroblast growth factor 23 (FGF-23), and growth hormone. Beginning in CKD stage 3, the ability of the kidneys to appropriately excrete a phosphate load is diminished, leading to hyperphosphatemia, elevated PTH (secondary hyperparathyroidism), and decreased 1,25(OH)2 vitamin D with associated elevations in the levels of FGF-23. The conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D is impaired, reducing intestinal calcium absorption and increasing PTH. The kidney fails to respond adequately to PTH, which normally promotes phosphaturia and calcium reabsorption, or to FGF-23, which also enhances phosphate excretion. In addition, there is evidence at the tissue level of a downregulation of vitamin D receptor and of resistance to the actions of PTH. Therapy is generally focused on correcting biochemical and hormonal abnormalities in an effort to limit their consequences.