title: Parathyroid hormone metabolism and signaling in health and chronic kidney disease.
abstract: Circulating parathyroid hormone (PTH) shows a complex relationship with hard outcomes in subjects with chronic kidney disease (CKD). Moreover, intervention studies directly targeting PTH failed to yield unequivocal results. Disturbed PTH metabolism, posttranslational modifications of PTH, and end-organ hyporesponsiveness to PTH may explain the poor performance of PTH as an outcome biomarker and precise target of therapy in the setting of CKD, at least in the gray middle target zone. PTH fragments accumulate in CKD patients and may exert effects that are distinct from, if not opposite to biointact (1-84)PTH. Posttranslational modification of PTH and especially oxidation may alter the interaction of PTH with its receptor. Its clinical relevance, however, remains a matter of ongoing debate. Less controversial is the issue of end-organ hyporesponsiveness to PTH. This phenomenon, formally referred to as PTH resistance, has long been recognized in CKD, but factors and mechanisms contributing to it remain poorly defined. Subsequent evidence identified downregulation of the PTH receptor and competing downstream signals as underlying pathophysiologic mechanisms. End-organ hyporesponsiveness to PTH in CKD, along with important analytical and biological variability, renders defining the PTH target range in CKD challenging. Although this may still be accomplished at the population level, it may prove to be very difficult at the individual level. This is a disillusioning thought in an era of personalized medicine. Parallel to the search of a functional and readily available assay quantifying PTH signaling tone or sensitivity, additional biomarkers (or a panel of biomarkers) should be formally evaluated.
authors.affiliation: KU Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology and University Hospitals Leuven, Department of Nephrology and Renal Transplantation, B-3000 Leuven, Belgium; Board member of the ERA-EDTA CKD-MBD Working Group. Electronic address: Pieter.Evenepoel@uzleuven.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: Fundació Puigvert, Department of Nephrology, IIB Sant Pau, RedinREn, Barcelona, Catalonia, Spain; Board member of the ERA-EDTA CKD-MBD Working Group.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bover
authors.affiliation: Ramsay-Générale de Santé, Clinique du Landy, Service de Néphrologie-Dialyse, Saint Ouen, France, INSERM U1151-CNRS UMR8253 Université Paris Descartes, and Service des Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, Paris, France; Board member of the ERA-EDTA CKD-MBD Working Group.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ureña Torres
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D010281:Parathyroid Hormone / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone
keywords: CKD; hyperparathyroidism; mineral metabolism; parathyroid hormone