Taking aim at targets

Since the mid-1990s, many studies showing increased mortality with higher serum calcium, phosphorus and parathyroid hormone (PTH) levels in dialysis-dependent patients have been reported. By 2003, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) released guidelines for mineral metabolism for all stages of chronic kidney disease (CKD) that have been influential in determining practice patterns. For stage 5 CKD (estimated GFR <15 ml/min/1.73 m 2 ), these guidelines prescribed serum targets of 16.5–33 pmol/l (150–300 pg/ml) for PTH, 1.1–1.8 mmol/l (3.5–5.5 mg/dl) for phosphorus and 2.1–2.4 mmol/l (8.4–9.5 mg/dl) for calcium. Target ranges for serum calcium, phosphorus and PTH were developed by K/DOQI based on the available literature of the time and have been both standard practice for clinical care and primary outcomes for research ever since. While the majority of early reports linking mineral metabolism to survival were related to dialysis patients, subsequent observational analyses confirmed similar associations in all CKD stages, kidney transplant recipients and other populations. Given the apparent link between mineral metabolism and patient-level outcomes in CKD, an expanding pharmaceutical armamentarium (vitamin D compounds, phosphate binders and calcimimetics) has become available; since publication of the K/DOQI guidelines on bone and mineral metabolism the use of these drugs has increased significantly, as have the related costs.