Chronic Kidney Disease–Mineral and Bone Disorders

Chronic kidney disease (CKD) is accompanied by diverse complications involving bone and mineral metabolism that have implications for skeletal and cardiovascular health. Understanding the highly varied pathophysiology of these co-morbidities can yield insights into management of patients with CKD. Serum calcium levels are maintained within a narrow normal range through regulatory mechanisms involving the parathyroid gland, bone, kidney, and intestines that rapidly respond to even small changes. In contrast, the homeostatic regulation of phosphate homeostasis is less precise and not rapid. Abnormal function of any of these systems can lead to disorders of calcium and phosphorus homeostasis, with consequential effects on bone and vascular health. During early stages of chronic kidney disease (CKD), fibroblast growth factor-23 (FGF-23) and subsequently parathyroid hormone (PTH) increase to prevent hyperphosphatemia. However, since FGF23 reduces the formation and increases the metabolism of 1,25(OH)₂ vitamin, it is mainly PTH that helps prevent hypocalcemia. As the decline in glomerular filtration rate (GFR) approaches end-stage kidney disease (ESKD), patients with CKD manifest elevated phosphorus, FGF-23, and PTH levels, which contribute to CKD-mineral bone disorder (CKD-MBD). Partly as a result of these skeletal abnormalities, patients with CKD have a more than fourfold higher risk of fractures than the general population, which progressively increases at more advanced CKD stages. In addition, vascular calcifications, closely linked to CKD-MBD, are commonly present in CKD patients and are associated with cardiovascular mortality. Therefore, the understanding and treatment of CKD-MBD are of substantial interest for clinicians.