title: The challenge of controlling phosphorus in chronic kidney disease.
abstract: The pathogenesis and management of chronic kidney disease-mineral bone disorders (CKD-MBD) has experienced major changes, but the control of serum phosphorus at all stages of CKD still seems to be a key factor to improve clinical outcomes. High serum phosphorus is the most important uremia-related, non-traditional risk factor associated with vascular calcification in CKD patients and in the general population. Phosphorus may also be one of the key elements linking vascular calcification with low bone turnover. The main hormones and factors that contribute to the kidney regulation of phosphorus and calcium include parathyroid hormone, FGF-23, klotho and 1,25-dihydroxyvitamin D (1,25(OH)2D). Serum phosphorus did not start rising until CKD 3b in contrast with the earlier changes observed with fibroblast growth factor-23 (FGF-23), Klotho, calcitriol and parathyroid hormone (PTH). Despite FGF-23 and PTH having synergic effects regarding phosphorus removal, they have opposite effects on 1,25(OH)2D3. At the same stages of CKD in which phosphorus retention appears to occur, calcium retention also occurs. As phosphorus accumulation is associated with poor outcomes, an important question without a clear answer is at which level-range should serum phosphorus be maintained at different stages of CKD to improve clinical outcomes. There are four main strategies to manage phosphate homeostasis; phosphorus dietary intake, administration of phosphate binder agents, effective control of hyperparathyroidism and to ensure in the CKD 5D setting, an adequate scheme of dialysis. Despite all the available strategies, and the introduction of new phosphate binder agents in the market, controlling serum phosphorus remains challenging, and hyperphosphatemia continues to be extremely common in CKD 5 patients. Furthermore, despite phosphate binding agents having proved to be effective in reducing serum phosphorus, their ultimate effects on clinical outcomes remain controversial. Thus, we still need well-designed, large-scale, placebo-controlled studies to definitively prove that the reduction of serum phosphorus by phosphate binders improves clinical outcomes.
authors.affiliation: Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, University of Oviedo, Asturias, Spain.
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Cannata-Andía
authors.affiliation: Division of Nephrology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Martin
mesh_terms: D000089703:Fibroblast Growth Factor-23; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010758:Phosphorus / Q000097:blood*; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*
chemical_list: C000717427:FGF23 protein, human; D016226:Phosphorus, Dietary; D010758:Phosphorus; D000089703:Fibroblast Growth Factor-23
keywords: chronic kidney disease; clinical management; hyperphosphatemia; phosphate control