Abstract
Arginine vasopressin (AVP) plays a key role in maintaining fluid balance and vascular tone and is useful in diagnosing diabetes insipidus (DI) and polyuria-polydipsia. Central DI is characterized by decreased AVP secretion leading to polyuria and polydipsia caused by diminished renal ability to concentrate urine. Alternatively, nephrogenic DI is characterized by a decrease in the ability to concentrate urine because of resistance of the distal nephron to AVP action. While AVP measurement can be diagnostic, reliable measurement of AVP can be hindered by several factors. AVP is tightly bound to platelets and is influenced by their number and incomplete removal, as well as pre-analytical processing. In addition, AVP is also highly unstable in isolated plasma - even at frozen temperatures. Copeptin comprises the C-terminal portion of the AVP precursor “pre-pro-vasopressin”. Equimolar amounts of AVP and copeptin released from this precursor during prohormone processing. Unlike the AVP molecule, copeptin is stable at room and refrigerated temperatures. In the current study, our objective was to confirm that copeptin can serve as a sensitive surrogate marker for AVP release in diagnosis. Our laboratory validated the B·R·A·H·M·S™ Copeptin proAVP assay on the automated KRYPTOR® platform. The measuring principle of the assay is based on Time-Resolved Amplified Cryptate Emission (TRACE®) technology, which measures the signal that is emitted with time delay from an immunocomplex. The molecules of copeptin present in the patient samples are sandwiched between the antibodies of the immunoassay. The intensity of the signal is proportional to the amount of copeptin. Extensive comparison studies, between AVP and copeptin, were conducted during the assay validation process. Approximately 245 patient samples previously tested for AVP were also tested in the copeptin assay. Using the respective reference intervals (RI) for AVP and copeptin, there was a 78.3% clinical concordance between the 2 assays; 53 samples (21.6%) were clinically discordant. Of the 245 patients, 4.5% (11 ) were above the AVP RI and 22.9% (56) were above the copeptin RI. Correlation plots showed a large degree of scatter between AVP and copeptin, which likely reflects the dissimilar stabilities of the two analytes. In conclusion, validation data suggest that there is clinical concordance for most patients tested using copeptin and AVP assays.