Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease

Abstract

Background: There are significant differences in plasma parathyroid hormone (PTH) results obtained by current immunoassay methods. However, many clinical guidelines relevant to patients with chronic kidney disease (CKD) that recommend PTH target values do not take account of these differences. This raises major questions about the validity of the evidence underpinning current use of PTH measurements in the management of CKD as well as of published relevant audit data. Methods: PTH was measured in plasma from patients with CKD in six commercially available immunoassays. The initial pilot study included 19 patients while 98 patients were included in a second extended study. Data from the second study were analysed by regression analysis to obtain assay-specific targets for each immunoassay. Results: Although similar PTH reference intervals are provided by most manufacturers, both studies confirmed substantial between-method differences in observed PTH for all patients, with results varying by as much as 4.2-fold between the lowest and highest reading methods. These differences were sufficient to have treatment implications for 79% of the patients in the pilot study. Applying the assay-specific targets derived here to results from the extended study decreased treatment misclassifications from 53% to 12%. Conclusions: Existing between-method differences in PTH measurements clearly have treatment implications. International initiatives to address these differences are in progress and will require support and input from all stakeholders. Adoption of assay-specific target values such as those reported here provides a convenient and practical interim solution that should lead to significant improvement in patient management, while also enabling meaningful audit.

Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review

“…Results from proficiency testing schemes demonstrate marked between-method differences in PTH results which parallel the more than three-times the differences that can be observed in the same sample from patients with CKD-MBD [5]. Such variability represents significant clinical risk, which could result in opposite decisions, e.g., concerning whether or not a patient receives vitamin D treatment, cinacalcet or parathyroidectomy, depending upon the PTH method used.…”

Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids

“…Several proposals have been reported, ranging from 20 L [48] to 1000 ng/L [50]; some authors, to simplify the matter, have suggested considering positive any FNA-PTH value higher than the respective serum PTH concentration [51,53,60,64,65,67]. To avoid misclassification due to circadian and seasonal rhythms and to physical exercise [69], which can influence serum PTH concentrations, and blood contamination which can potentially affect FNA-PTH levels, we suggest as positive cutoff the FNA-PTH/serum PTH ratio ≥ 2 (Table 6). We also advise to measure FNA-PTH in the same laboratory with the same sample preparation and the same IMA method [70,71].…”

LC-MS candidate reference methods for the harmonisation of parathyroid hormone (PTH) measurement: a review of recent developments and future considerations

“…Current PTH testing inadequacies are of grave concern for patients with renal failure, with potential influences on patient misclassification, inappropriate treatment outcomes and patient management [16,17]. The establishment of the IFCC working group is an important step towards this goal, as are the analytical developments discussed in this review.…”

“…The variability which exists in PTH testing should be considered a critical governance issue in patients with chronic kidney disease [16]. Given this variability in results produced using different methodologies, some clinicians question the relevance of [2,17]. Often, assay preference is governed more by reliance upon a method with which they have the most familiarity and clinical experience than by absolute analytical accuracy [8].…”