Changes in the metabolism of calcium, phosphat, parathyroid hormone and vitamin D typically start to occur once GFR ≤ 60 ml/min/1,73m2. As kidney function decreases, the kidney clearance of phosphate is diminished, leading to higher serum phosphate levels. Level of calcitriol, the most active form of vitamin D, fall because kidney function is required for its synthesis. Calcium levels may fall as a result of less vitamin D dependent calcium uptake from the gastrointestinal tract. The combined effects of higher phosphate, lower calcium and lower vitamin D levels all serve to stimulate parathyroid hormone production, and in turn elevated levels of PTH increase the resorption and release of mineral from bone. These changes are associated with an increased risk of fracture and also increased cardiovascular mortality, perhaps mediated by accelerated vascular calcification.