The pathogenesis is conceptualized through a 'two-hit' model: the systemic 'first hit' involves the specific milieu of chronic kidney disease-mineral and bone disorder driven by hyperphosphataemia, calcium load, secondary hyperparathyroidism and a critical deficiency in calcification inhibitors such as fetuin-A and Klotho. The gene discussed is AHSG; the disease is secondary hyperparathyroidism.