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

Clara Odilia Sailer, Julie Refardt, Claudine Angela Blum, Ingeborg Schnyder, Jose Alberto Molina-Tijeras, Wiebke Fenske, Mirjam Christ-Crain, Clara Odilia Sailer, Julie Refardt, Claudine Angela Blum, Ingeborg Schnyder, Jose Alberto Molina-Tijeras, Wiebke Fenske, Mirjam Christ-Crain

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.

Conflict of interest statement

MCC received speaking honoraria from Thermo Fisher Scientific, the manufacturer of Brahms Copeptin proAVP KRYPTOR and Brahms CT-proAVP LIA assay. The other authors declare no competing interests.

Figures

Figure 1
Figure 1
Intra-assay difference in copeptin concentrations in healthy volunteers. Bland–Altman graph of intra-assay difference in copeptin concentrations in healthy volunteers for (a) the KRYPTOR, (b) the LIA and (c) the ELISA. The dotted middle line represents the mean difference in copeptin concentrations between the two different assays (a): − 0.08 pmol/l (95% limits − 0.75 to 0.48), (b): − 0.55 pmol/l (95% limits − 6.69 to 5.59), (c): 0.92 pmol/l (95% limits − 17.32 to 19.16)). The outer dotted lines represent the 95% confident interval limits of agreement. (a) KRYPTOR 1 vs KRYPTOR 2, (b) LIA 1 vs LIA 2, (c) ELISA 1 vs ELISA 2.
Figure 2
Figure 2
Inter-assay difference in copeptin concentrations in healthy volunteers. Bland–Altman graph of inter-assay difference in copeptin concentrations in healthy volunteers for (a) the KRYPTOR vs LIA, (b) the KRYPTOR vs ELISA and (c) the LIA vs ELISA. The dotted middle line represents the mean difference in copeptin concentrations between the two different assays ((a): 5.51 pmol/l (95% limits − 4.16 to 15.18), (b): − 30.8 pmol/l (95% limits − 60.63 to − 1.03), (c): − 36.34 pmol/l (95% limits − 63.37 to − 9.32)). The outer dotted lines represent the 95% confident interval limits of agreement. (a) KRYPTOR vs LIA, (b) KRYPTOR vs ELISA, (c) LIA vs ELISA.

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Source: PubMed

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