Background and objectives: Clinical management of mineral bone disorder in patients with kidney failure is guided by biochemical targets, in particular parathyroid hormone (PTH) concentration. The biologic variation of PTH and other bone mineral markers was measured in hemodialysis patients to better define their role in management.Design, setting, participants, & measurements: Intact PTH, biointact (whole-molecule) PTH, calcium, albumin-adjusted calcium, phosphate, and alkaline phosphatase (ALP) were measured in nonfasting samples obtained twice a week (both short-dialysis interval) over a 6-week period in 22 stable hemodialysis patients. Concurrently, samples were obtained from 12 healthy volunteers. Intraindividual coefficients of variance (CV I ) were calculated and used to derive the reference change value (RCV) required to be 95% certain that a change has occurred.Results: CV I of all markers was significantly (P < 0.05) greater in patients than in healthy volunteers. For phosphate, ALP, and PTH this implies that an increased number of samples is required to estimate an individual's homeostatic set point. CV I of intact PTH was 25.6% in hemodialysis patients and 19.2% in healthy volunteers. A greater RCV should be used for patients (72%) compared with healthy volunteers (54%). Ideally 26 specimens should be measured to estimate a patient's intact PTH homeostatic set point (within ؎10%) with 95% probability. The CV I of biointact PTH was at least as high as that for intact PTH.Conclusions: The uncertainty of PTH estimation in an individual significantly undermines its value as a tool in the management of chronic kidney disease-mineral bone disorder using current management approaches.

Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease–mineral and bone disorder.