Inter-method variability in PTH measurement: implication for the care of CKD patients

Area of Science:

• Clinical Chemistry
• Nephrology
• Biochemistry

Background:

• The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative (NKF/KDOQI) guidelines suggest target serum intact parathyroid hormone (PTH) levels for chronic kidney disease (CKD) stage 5 patients.
• These guidelines were established using the Allegro intact PTH assay, necessitating an evaluation of their applicability to other commercially available assays.

Purpose of the Study:

• To assess the comparability of 15 different commercial immunoassays for intact PTH measurement against the Allegro intact PTH assay.
• To determine the impact of inter-assay variability on achieving recommended PTH target ranges in CKD patients.

Main Methods:

• Comparison of PTH concentrations from 47 serum pools from dialysis patients using 15 commercial immunoassays against the Allegro intact PTH assay as a reference.
• Evaluation of the recovery of synthetic 1-84 and 7-84 PTH added to serum pools to assess assay specificity and cross-reactivity.

Main Results:

• While assays showed high correlation, significant differences in PTH concentrations were observed, with median biases ranging from -44.9% to 123.0% compared to the Allegro assay.
• PTH levels of 150-300 ng/l on the Allegro assay translated to a wide range (83-323 ng/l and 160-638 ng/l, respectively) on other assays.
• Inter-method variability was attributed to differences in antibody specificity and standardization, affecting the recognition of different PTH fragments (e.g., 7-84 PTH) and recovery of 1-84 PTH.

Conclusions:

• There is substantial inter-method variability in intact PTH measurements across different commercial immunoassays.
• This variability can lead to discordant therapeutic decisions for CKD patients depending on the assay used.
• The study recommends implementing assay-specific decision limits or correcting factors for PTH results in CKD management.