Laboratory abnormalities in CKD-MBD: markers, predictors, or mediators of disease?

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and an array of laboratory abnormalities. The latter classically include disturbances in the parathyroid hormone/vitamin D axis. More recently, fibroblast growth factor 23 (FGF23) and klotho also have been identified as important regulators of mineral metabolism. Klotho deficiency and high circulating FGF23 levels precede secondary hyperparathyroidism in CKD patients. Levels of FGF23 and parathyroid hormone increase along the progression of CKD to maintain mineral homeostasis and to overcome end-organ resistance. It is hard to define when the increase of both hormones becomes maladaptive. CKD-MBD is associated with adverse outcomes including cardiovascular disease and mortality. This review summarizes the complex pathophysiology of CKD-MBD and outlines which laboratory abnormalities represent biomarkers of disease severity, which laboratory abnormalities are predictors of cardiovascular disease, and which laboratory abnormalities should be considered (direct) uremic toxins exerting organ damage. This information may help to streamline current and future therapeutic efforts.