Parathyroid hormone assays--evolution and revolutions in the care of dialysis patients

Renal osteodystrophy may present with low, normal, or high bone turnover. An ideal parathyroid hormone (PTH) assay should discriminate between the bioactive whole PTH-(1-84) molecule and PTH fragments, including the PTH-(7-84) fragment. Most dialysis patients have "intact" PTH (iPTH) levels between 65 and 450 pg/ml, which are poorly predictive of bone turnover state, making the iPTH test of limited value for bone turnover prediction. iPTH levels higher than 500 pg/ml can be observed in some dialysis patients with low bone turnover, while iPTH levels as low as 100 pg/ml have been found in patients with bone turnover above normal, indicating the standard second generation iPTH assay is not a reliable sole indicator of bone turnover. The whole PTH immunoradiometric assay, a third generation assay, uses a detection antibody that recognizes antigenic determinants at the extreme amino-terminal (1-4) end of the PTH molecule, making the assay specific for biologically active whole PTH-(1-84). Comparing results using the whole PTH and iPTH assays, the PTH-(7-84) level is indirectly determined and the PTH-(1-84)/PTH-(7-84) ratio can be calculated. It was shown that PTH-(7-84) inhibits the calcemic effect of PTH-(1-84) and its stimulatory effect on bone turnover. In the interpretation of results using the PTH-(1-84)/PTH-(7-84) ratio, it must be taken into consideration that second generation "intact" PTH assays have different cross-reactivity with PTH-(7-84). Therefore, when comparing or analyzing PTH-(1-84)/PTH-(7-84) ratios, the employed PTH assays must be identical. The whole PTH assay and the PTH-(1-84)/PTH-(7-84) ratio allow more meaningful interpretation of PTH trends, and offer a non-invasive means to more accurately diagnose bone disease in this population.