Copeptin levels and commonly used laboratory parameters in hospitalised patients with severe hypernatraemia - the “Co-MED study”

Abstract

BackgroundHypernatraemia is common in inpatients and is associated with substantial morbidity. Its differential diagnosis is challenging, and delayed treatment may have devastating consequences. The most important hormone for the regulation of water homeostasis is arginine vasopressin, and copeptin, the C-terminal portion of the precursor peptide of arginine vasopressin, might be a reliable new parameter with which to assess the underlying cause of hypernatraemia.MethodsIn this prospective, multicentre, observational study conducted in two tertiary referral centres in Switzerland, 92 patients with severe hyperosmolar hypernatraemia (Na+ > 155 mmol/L) were included. After a standardised diagnostic evaluation, the underlying cause of hypernatraemia was identified and copeptin levels were measured.ResultsThe most common aetiology of hypernatraemia was dehydration (DH) (n = 65 [71%]), followed by salt overload (SO) (n = 20 [22%]), central diabetes insipidus (CDI) (n = 5 [5%]) and nephrogenic diabetes insipidus (NDI) (n = 2 [2%]). Low urine osmolality was indicative for patients with CDI and NDI (P < 0.01). Patients with CDI had lower copeptin levels than patients with DH or SO (both P < 0.01) or those with NDI. Copeptin identified CDI with an AUC of 0.99 (95% CI 0.97–1.00), and a cut-off value ≤ 4.4pmol/L showed a sensitivity of 100% and a specificity of 99% to predict CDI. Similarly, urea values were lower in CDI than in DH or SO (P < 0.05 and P < 0.01, respectively) or NDI. The AUC for diagnosing CDI was 0.98 (95% CI 0.96–1.00), and a cut-off value < 5.05 mmol/L showed high specificity and sensitivity for the diagnosis of CDI (98% and 100%, respectively). Copeptin and urea could not differentiate hypernatraemia induced by DH from that induced by SO (P = 0.66 and P = 0.30, respectively).ConclusionsCopeptin and urea reliably identify patients with CDI and are therefore helpful tools for therapeutic management in patients with severe hypernatraemia.Trials registrationClinicalTrials.gov, NCT01456533. Registered on 20 October 2011.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-1955-7) contains supplementary material, which is available to authorized users.

Sevoflurane and nephrogenic diabetes insipidus on the rise: copeptin to the rescue?

“…One of their main findings was an evidently higher copeptin levels in nephrogenic diabetes insipidus (NDI), compared to central diabetes insipidus (CDI). When choosing a cutoff value of < 4.4 pmol/L, copeptin levels had a sensitivity of 100% and a specificity of 99% for diagnosing CDI, whereas the values for NDI were approximately 18 times higher [1]. These findings confirmed the results of an earlier study by Timper et al [2].…”

“…With interest, we read the recent paper by Nigro et al on the differential diagnosis of hypernatremia in intensive care unit (ICU) [1]. One of their main findings was an evidently higher copeptin levels in nephrogenic diabetes insipidus (NDI), compared to central diabetes insipidus (CDI).…”

“…Alternatively inorganic fluoride produced with hexafluoroisopropanolol during sevoflurane metabolism by cytochrome P450 may be toxic [4]. The differential diagnosis between NDI and CDI can be problematic as both groups may present with neurological problems [1]. Only a trial dose of desmopressin could differentiate as most but not all with NDI will remain unresponsive [3, 4].…”

“…Only a trial dose of desmopressin could differentiate as most but not all with NDI will remain unresponsive [3, 4]. Copeptin may resolve the diagnosis dilemma [1] allowing institution of appropriate treatment, either by removal of the cause (sevoflurane) or the treatment of the causality (brain edema, cerebral bleeding, etc.). In summary, as long as sevoflurane use increases and in the knowledge that 20% of these cases develop NDI, copeptin is a valuable tool permitting a rapid and definitive differential diagnosis between CDI and NDI.…”

Associations of cardiac stress biomarkers with incident type 2 diabetes and changes in glucose metabolism: KORA F4/FF4 study

“…Similarly, low MR-proANP levels were associated with incident T2D [ 8 , 11 ]. Conversely, copeptin, that is commonly known as a biomarker for diabetes insipidus [ 12 , 13 ], was positively associated with incident T2D in some studies [ 14 – 16 ], but others observed this positive association only in women [ 17 ]. In comparison to NT-proBNP, MR-proANP and copeptin have been less widely investigated regarding their roles in the development of T2D.…”