title: Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?
abstract: The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) does not appear to fulfil the requirements for a syndrome at first glance, but its definition has brought some clear-cut benefits for clinicians and patients, including wider and more complex diagnostic and therapeutic approaches to the management of this challenging set of issues. Admittedly, not all components of CKD-MBD are present in all patients at all times, but these are highly interrelated, involving mineral and bone laboratory abnormalities, clinical and histological bone disease and finally, cardiovascular disease. The presence of typical biological bone ossification processes in an ectopic anatomical location in CKD has helped to define the existence of an unprecedented bone-vascular relationship, extending its interest even to other medical specialities. For now, we believe that CKD-MBD does not reach full criteria to be defined as a syndrome. However, this novel concept has clearly influenced current clinical guidelines. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) guidelines in 2003 for instance recommended that calcium-based phosphate binders should be avoided to treat hyperphosphataemia in the presence of cardiovascular calcifications. In 2009, the KDIGO and other guidelines reinforced and extended this recommendation by stating that it is reasonable to choose oral phosphate binder therapy by taking into consideration other components of CKD-MBD. Similarly, it is also considered reasonable to use information on vascular/valvular calcification to guide the management of CKD-MBD. Our current assumption as a working group 'CKD-MBD' is that CKD-MBD has the potential to be defined a true syndrome, such as a constellation of concurrent signs and symptoms that suggest a common underlying mechanism for these components as opposed to the term disease. The term 'syndrome' also implies that in any patient at risk due to the presence of one or a few components of the entire syndrome, the screening for additional components is highly recommended. However, it has not currently been demonstrated that there is an additive predictive value, which can be derived from identifying individual components. Despite all we have learned about this putative syndrome, we have been left with only a hypothetical framework about how to treat patients. So while we agree that the concept of CKD-MBD has influenced, and continues to influence, our current clinical hypotheses, definitive proof of a benefit of interventions in CKD-MBD is still lacking and a global-multiple therapeutic approach to treat simultaneously several components of CKD-MBD should be tested by well-designed new randomized controlled trials.
authors: Department of Health Sciences, Renal Division and Laboratory of Experimental Nephrology, San Paolo Hospital, University of Milan, Milan, Italy.
authors: Mario
authors: M
authors: Cozzolino
authors: Department of Nephrology and Dialysis, Clinique du Landy and Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France.
authors: Pablo
authors: P
authors: Ureña-Torres
authors: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Marc G
authors: MG
authors: Vervloet
authors: Department of Cardiology and Intensive Care Medicine, RWTH University Hospital Aachen, Aachen, Germany.
authors: Vincent
authors: V
authors: Brandenburg
authors: Department of Nephrology, Fundació Puigvert, IIB Sant Pau, REDinREN, Barcelona, Spain.
authors: Jordi
authors: J
authors: Bover
authors: King's Health Partners AHSC London, London, UK.
authors: David
authors: D
authors: Goldsmith
authors: Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institutet, Stockholm, Sweden Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
authors: Tobias E
authors: TE
authors: Larsson
authors: Division of Nephrology, Ambroise Paré Hospital, Paris Ile de France Ouest University (UVSQ), Paris, France INSERM U1088, Picardie University Jules Verne (UPJV), Amiens, France.
authors: Ziad A
authors: ZA
authors: Massy
authors: Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
authors: Sandro
authors: S
authors: Mazzaferro
mesh_terms: D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D054559:Hyperphosphatemia / Q000378:metabolism / Q000473:pathology*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology*; D013577:Syndrome
keywords: cardiovascular outcome; chronic kidney disease; parathyroid hormone; renal osteodystrophy; syndrome