Chronic kidney disease–mineral and bone disorder as multidimensional bone–vascular risk framework: from biochemical control to risk-and context-guided care

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic complication that spans early CKD, dialysis and kidney transplantation. It is better understood not as an isolated disturbance of calcium and phosphate metabolism but as a multidimensional, dynamic syndrome in which mineral-endocrine dysregulation, skeletal remodeling, skeletal fragility and structural consequences, and vascular calcification interact to shape patient outcomes. This narrative review argues that management should move beyond the control of biochemical targets toward phenotype-informed, evidence-graded and outcome-oriented care organized around the bone–vascular axis. We first examine why surrogate-based management has under performed and then propose a working multidimensional framework based on four interrelated domains mineral and endocrine status, bone turnover and mineralization, skeletal fragility and structural consequences, vascular calcification and cardiovascular risk, and clinical modifiers and treatment context. We also grade the evidence behind the principal mechanisms and interventions, from phosphate retention, the FGF23-Klotho axis, vitamin D-PTH dysregulation, Wnt/β-catenin signaling and calciprotein particles to inflammation, gut dysbiosis and uremic toxins, distinguishing mechanistic plausibility from observational association, surrogate-endpoint trials and hard-endpoint benefit. We then match diagnostic tools, including bone turnover markers, DXA, HR-pQCT, 18F-NaF PET/CT, vascular calcification scoring, calcification propensity testing and bone biopsy, to the clinical decisions they are meant to inform, and reframe treatment of hyperphosphatemia, secondary hyperparathyroidism, CKD-associated osteoporosis and vascular calcification by multidimensional framework. The recurring theme is that biochemical improvement is not itself benefit: the field needs stratified, testable strategies anchored in fracture, cardiovascular events, hospitalization, mortality, quality of life and physical function.