Third-generation parathyroid hormone assays and all-cause mortality in incident dialysis patients: The CHOICE study

Background. There has been controversy about the utility of new third-generation parathyroid hormone (PTH) assays measuring only 1-84 PTH, with few large studies comparing second- and third-generation PTH measurements in patients with ESRD. Methods. We measured 1-84 PTH ('biointact' or 'whole' PTH) and total PTH ('intact' PTH) in a national cohort of 515 incident dialysis patients from banked frozen EDTA plasma (median follow-up, 35 months) and examined the accuracy of estimating 1-84 PTH from total PTH and the associations of these levels with patient characteristics and mortality. Results. The 1-84 PTH and total PTH levels were closely correlated. Higher 1-84 PTH was associated with African-American race and higher serum phosphate and lower calcium levels. The percentage of total PTH represented by 1-84 PTH was, on average, 53%, but with a wide range (25-89%). Calculating 1-84 PTH from total PTH using a proposed standard conversion factor (54%) led to misclassification of 8% of the population compared with measured 1-84 PTH. In a multivariate Cox proportional hazards model for all-cause mortality, a 1-84 PTH value >160 pg/ml was associated with increased risk of mortality (HR = 1.62, 95% CI, 1.03-2.54) compared to a level of 80-160 pg/ml. Elevated total PTH, 7-84 PTH and the 1-84 PTH/7-84 PTH ratio were not significantly associated with mortality. Conclusions. The 1-84 PTH and total PTH are highly correlated. Elevated 1-84 PTH was significantly associated with increased mortality, whereas total PTH did not reach statistical significance. Thus, although in other respect they are similar, there may be utility in measuring 1-84 PTH for its associations with mortality.