Critical issues of PTH assays in CKD.

Measurement of bioactive parathyroid hormone (PTH) is essential for the optimal management of secondary hyperparathyroidism and its associated bone disorders in chronic kidney disease (CKD) patients. For this purpose, three generations of increasingly specific PTH assays have been developed over the last 4 decades. To date, however, only second-generation PTH assays are most widely used, although these have been shown to cross-react with large PTH fragments having a partially preserved N-structure, mostly PTH(7-84). The newly developed third-generation PTH assays are believed to be the most specific means of measuring PTH(1-84), but their clinical utility remains debatable. More recently, these latter assays have also been shown to react with a new N-form of PTH, which has been identified in patients with severe hyperparathyroidism and parathyroid carcinoma. Progressive research in this area has advanced our understanding considerably regarding the circulating molecular forms of PTH and their pathophysiological roles in bone abnormalities associated with CKD. However, developing an ideal PTH assay continues to be difficult because of key issues such as the reliability of PTH as a surrogate marker for bone turnover, practicality of employing third-generation PTH assays, and unknown biological implications of N-PTH and other PTH fragments. Further research exploring these issues is mandatory to understand and optimally manage parathyroid disorders and bone abnormalities in CKD patients.