Bone-specific alkaline phosphatase concentrations are less variable than those of parathyroid hormone in stable hemodialysis patients

Abstract

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.

Biomarkers Predicting Bone Turnover in the Setting of CKD

“…BsAP has features consistent with a promising biomarker: liver clearance (thus Fig. 1 Bone biomarkers concentrations not influenced by decreased glomerular filtration rate (GFR)), relative high half-life in serum, storage stability, and relatively low intra-individual (biological) variability [14,15,33]. In recent years, rapid, robust, and reproducible immunoassays have been developed for the quantification of circulating BsAP, often on fully automated platforms.…”

“…Unfortunately, most manufacturers do not take these confounding factors into consideration, which may lead to normal reference ranges which are wide with both too high upper and lower limits. Another post-analytical issue that should be accounted for is the biological variability (CVi) [14,15]. The CVi is the random natural variation around an individual homeostatic set point.…”

Renal osteodystrophy in children

“…Although longitudinal data are scarce, bone alkaline phosphatase measurement shows less variability than PTH [50,51]. Although longitudinal data are scarce, bone alkaline phosphatase measurement shows less variability than PTH [50,51].…”

Alkaline phosphatase: Better than PTH as a marker of cardiovascular and bone disease?

“…Intuitively, it makes sense to measure an enzyme that is directly involved in bone and vascular wall activity in our assessment of CKD‐MBD, as compared with PTH that is fundamentally more reflective of parathyroid gland activity than bone remodeling . As a potential biomarker of CKD‐MBD, ALP may be superior compared with PTH as it shows less within‐individual biological variation . PTH has a very short half‐life of 2–4 minutes, whereas bone ALP has a half‐life of 1.5–2.3 days and the liver isoform has a half‐life of 5–9 days .…”