Validity of different copeptin assays in the differential diagnosis of the polyuria-polydipsia syndrome

Abstract

The aim of this study was to correlate three commercially available copeptin assays and their diagnostic accuracy in the differential diagnosis of the polyuria-polydipsia syndrome. Analyzed data include repeated copeptin measures of 8 healthy volunteers and 40 patients with polyuria-polydipsia syndrome undergoing osmotic stimulation and of 40 patients hospitalized with pneumonia. Copeptin was measured using the automated Brahms KRYPTOR, the manual Brahms LIA and the manual Cloud Clone ELISA assay. Primary outcome was the interrater correlation coefficient (ICC) and diagnostic accuracy in the polyuria-polydipsia syndrome of the three assays. In healthy volunteers, there was a moderate correlation for the KRYPTOR and LIA (ICC 0.74; 95% CI 0.07 to 0.91), and a poor correlation for the KRYPTOR and ELISA (ICC 0.07; 95% CI − 0.06 to 0.29), as for the LIA and ELISA (ICC 0.04; 95% CI − 0.04 to 0.17). The KRYPTOR had the highest diagnostic accuracy (98% (95% CI 83 to100)), comparable to the LIA (88% (95% CI 74 to 100)), while the ELISA had a poor diagnostic accuracy (55% (95% CI 34 to 68)) in the differential diagnosis of the polyuria-polydipsia syndrome. The KRYPTOR and LIA yield comparable copeptin concentrations and high diagnostic accuracy, while the ELISA correlates poorly with the other two assays and shows a poor diagnostic accuracy for polyuria-polydipsia patients. The current copeptin cut-off is valid for the KRYPTOR and LIA assay. Our results indicate that interpretation with other assays should be performed with caution and separate validation studies are required before their use in differentiating patients with polyuria-polydipsia syndrome.Trial registration: NCT02647736 January 6, 2016/NCT01940614 September 12, 2013/NCT00973154 September 9, 2009.

Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus

“…In addition, the assays for measuring serum copeptin were different in that we used time-resolved amplified cryptate emission (TRACE) technology, while Fenske et al used a one-step assay with coated-tube technology. Although the copeptin levels measured by each method were comparable 26 , each method has different minimal detection limits and there are no international standardized calibration references. These reasons could possibly explain the discrepant copeptin cutoffs.…”

The diagnostic and prognostic value of copeptin in patients with acute ischemic stroke and transient ischemic attack: A systematic review and meta-analysis

“…The measuring method was specified in only 7 out of 17 studies eligible for analysis. Three of them used KRYPTOR test, which is the most appropriate according to the study conducted by Sailer et al [ 42 ] because it is highly accurate in non-healthy subjects. The sandwich-type immunoassay (ELISA) was used in 3 studies, and the CT-proAVP-luminescence-immunoassay was used in 1 study.…”

Approach to the Patient: “Utility of the Copeptin Assay”

“…In contrast, copeptin measured by the ELISA correlated only poorly with both the KRYPTOR and LIA measured copeptin concentrations. Importantly, for the current main indication of copeptin measurement (ie, differential diagnosis of polyuria polydipsia syndrome, see below) the cut-offs for copeptin have been developed and validated with the LIA and KRYPTOR assay; the ELISA has a poor diagnostic accuracy using these cut-offs, with an especially low sensitivity in correctly diagnosing patients with central diabetes insipidus ( 25 ). Therefore, for this indication, and also for other indications where cut-offs have been developed with KRYPTOR or LIA, further studies with development and validation of cut-offs are needed if the ELISA is used.…”