Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic condition arising from disturbances in mineral metabolism, bone architecture, and vascular calcification that accompany progressive renal function decline. The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD, produced with ISN support and published in Kidney International Supplements, provides the principal evidence-based framework for management of these disturbances across CKD stages.
ISN (International Society of Nephrology) has actively contributed to the KDIGO CKD-MBD guideline development process through its guideline working groups. Fibroblast growth factor 23 (FGF23) was identified as an early biomarker of phosphate dysregulation in CKD by Gutierrez et al. (New England Journal of Medicine, 2008), who demonstrated that elevated FGF23 was independently associated with mortality in incident hemodialysis patients, establishing it as a pathogenic mediator beyond its phosphaturic function.
The association between elevated FGF23 and left ventricular hypertrophy in CKD was demonstrated by Faul et al. (Journal of Clinical Investigation, 2011), who showed that FGF23 directly induces pathological cardiac hypertrophy through FGF receptor-dependent MAPK signaling in cardiomyocytes, independently of its known effects on phosphate and vitamin D metabolism. This mechanistic insight strengthened the scientific rationale for phosphate restriction and FGF23 reduction strategies in CKD.
Vascular calcification in CKD-MBD has been evaluated in epidemiological studies including the REIN-2 trial and observational cohorts within the SHARP trial population (Baigent et al., Lancet, 2011). The EVOLVE trial (Chertow et al., New England Journal of Medicine, 2012) evaluated cinacalcet for secondary hyperparathyroidism in hemodialysis patients, demonstrating significant reductions in FGF23 and vascular calcification markers, though the primary composite cardiovascular endpoint was not significantly different from placebo in the intention-to-treat analysis.
The International Society of Nephrology has highlighted unresolved questions in CKD-MBD management, including optimal PTH targets in dialysis patients and the evidence base for phosphate binders in reducing hard cardiovascular endpoints. ISN-supported registries including the Dialysis Outcomes and Practice Patterns Study (DOPPS) continue to provide real-world data on CKD-MBD management practices and outcomes across participating countries.