Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease–Mineral and Bone Disorder in Non-Dialysis Adult Patients

Abstract

Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease–mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.

Vitamin D: A Bridge between Kidney and Heart

“…Vitamin D is a key component of calcium/phosphate homeostasis and bone metabolism: in healthy subjects, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23) and Vitamin D act as deeply interlinked regulators of this delicate and complex physiological mechanism [57,58]. The disruptions in mineral metabolism caused by CKD, rising PTH, and lower Vitamin D levels are presently recognized as integral components of the chronic kidney disease-mineral and bone disorder (CKD-MBD) definition [59].…”

“…Subsequently, calcitriol deficiency will result in reduced calcium absorption from the intestine; to counteract this effect and avoid hypocalcemia, PTH activate osteoclasts thus reabsorbing calcium from the bone. In CKD, various mechanisms contribute to the overproduction of PTH, a condition known as secondary hyperparathyroidism (sHPT), a disease totally different from disorders in the parathyroid glands (primary HPT) [56,57].…”

“…The clinical implications of CKD-MBD involve parathyroid gland hyperplasia, bone abnormalities, and vascular calcification; as CKD progresses, the parathyroid glands undergo nodular hyperplasia due to persistent overstimulation by hypocalcemia and hyperphosphoremia [57,61,63,64]. The reduced sensitivity to vitamin D and calcium signals, attributed to the loss of respective receptors, further complicates the situation, leading to parathyroidectomy in the most severe cases [59,61,65].…”

Vitamin D: A Bridge between Kidney and Heart

“…Vitamin D is a key component of calcium/phosphate homeostasis and bone metabolism: in healthy subjects, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23), and vitamin D act as deeply interlinked regulators of this delicate and complex physiological mechanism [58,59]. The disruptions in mineral metabolism caused by CKD, rising PTH, and lower vitamin D levels are presently recognized as integral components of the chronic kidney disease-mineral and bone disorder (CKD-MBD) definition [60].…”

“…Subsequently, calcitriol deficiency will result in reduced calcium absorption from the intestine; to counteract this effect and avoid hypocalcemia, PTHs activate osteoclasts, thus reabsorbing calcium from the bone. In CKD, various mechanisms contribute to the overproduction of PTH, a condition known as secondary hyperparathyroidism (sHPT), a disease totally different from disorders in the parathyroid glands (primary HPT) [57,58].…”