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

Nicole Nigro, Bettina Winzeler, Isabelle Suter-Widmer, Philipp Schuetz, Birsen Arici, Martina Bally, Julie Refardt, Matthias Betz, Gani Gashi, Sandrine A Urwyler, Lukas Burget, Claudine A Blum, Andreas Bock, Andreas Huber, Beat Müller, Mirjam Christ-Crain, Nicole Nigro, Bettina Winzeler, Isabelle Suter-Widmer, Philipp Schuetz, Birsen Arici, Martina Bally, Julie Refardt, Matthias Betz, Gani Gashi, Sandrine A Urwyler, Lukas Burget, Claudine A Blum, Andreas Bock, Andreas Huber, Beat Müller, Mirjam Christ-Crain

Abstract

Background: Hypernatraemia 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.

Methods: In 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.

Results: The 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).

Conclusions: Copeptin and urea reliably identify patients with CDI and are therefore helpful tools for therapeutic management in patients with severe hypernatraemia.

Trials registration: ClinicalTrials.gov, NCT01456533 . Registered on 20 October 2011.

Keywords: Copeptin; Differential diagnosis; Severe hypernatraemia; Symptoms and characteristics.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Basel and Aarau. Informed consent was obtained from all patients or their next of kin before enrolment.

Consent for publication

Not applicable.

Competing interests

PS, BM and MCC have received speaker’s honoraria and research support from Thermo Scientific Biomarkers. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Copeptin levels in the differential diagnosis of hypernatraemia
Fig. 2
Fig. 2
Urea levels in the differential diagnosis of hypernatraemia

References

    1. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010;36(2):304–11. doi: 10.1007/s00134-009-1692-0.
    1. Hoorn EJ, Betjes MG, Weigel J, Zietse R. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant. 2008;23(5):1562–8. doi: 10.1093/ndt/gfm831.
    1. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493–9. doi: 10.1056/NEJM200005183422006.
    1. Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124(2):197–203. doi: 10.7326/0003-4819-124-2-199601150-00002.
    1. Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients: a heterogeneous, morbid, and iatrogenic entity. Ann Intern Med. 1987;107(3):309–19. doi: 10.7326/0003-4819-107-2-309.
    1. Mandal AK, Saklayen MG, Hillman NM, Markert RJ. Predictive factors for high mortality in hypernatremic patients. Am J Emerg Med. 1997;15(2):130–2. doi: 10.1016/S0735-6757(97)90082-6.
    1. Alshayeb HM, Showkat A, Babar F, Mangold T, Wall BM. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci. 2011;341(5):356–60. doi: 10.1097/MAJ.0b013e31820a3a90.
    1. Greenberg A, Verbalis JG, Amin AN, et al. Current treatment practice and outcomes: report of the Hyponatremia Registry. Kidney Int. 2015;88(1):167–77. doi: 10.1038/ki.2015.4.
    1. Chakko S, Woska D, Martinez H, et al. Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care. Am J Med. 1991;90(3):353–9. doi: 10.1016/0002-9343(91)80016-F.
    1. Chassagne P, Druesne L, Capet C, Menard JF, Bercoff E. Clinical presentation of hypernatremia in elderly patients: a case control study. J Am Geriatr Soc. 2006;54(8):1225–30. doi: 10.1111/j.1532-5415.2006.00807.x.
    1. Arampatzis S, Exadaktylos A, Buhl D, Zimmermann H, Lindner G. Dysnatraemias in the emergency room: undetected, untreated, unknown? Wien Klin Wochenschr. 2012;124(5-6):181–3. doi: 10.1007/s00508-011-0108-7.
    1. Morgenthaler NG, Muller B, Struck J, Bergmann A, Redl H, Christ-Crain M. Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock. Shock. 2007;28(2):219–26. doi: 10.1097/SHK.0b013e318033e5da.
    1. Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005;26(12):2500–4. doi: 10.1016/j.peptides.2005.04.019.
    1. Jochberger S, Morgenthaler NG, Mayr VD, et al. Copeptin and arginine vasopressin concentrations in critically ill patients. J Clin Endocrinol Metab. 2006;91(11):4381–6. doi: 10.1210/jc.2005-2830.
    1. Szinnai G, Morgenthaler NG, Berneis K, et al. Changes in plasma copeptin, the C-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects. J Clin Endocrinol Metab. 2007;92(10):3973–8. doi: 10.1210/jc.2007-0232.
    1. Morgenthaler NG, Struck J, Jochberger S, Dunser MW. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab. 2008;19(2):43–9. doi: 10.1016/j.tem.2007.11.001.
    1. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006;52(1):112–9. doi: 10.1373/clinchem.2005.060038.
    1. Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract. 2012;120(4):c179–84.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1).
    1. B∙R∙A∙H∙M∙S. Copeptin—the better vasopressin. . Accessed Aug 2016.
    1. Toor MR, Singla A, DeVita MV, Rosenstock JL, Michelis MF. Characteristics, therapies, and factors influencing outcomes of hospitalized hypernatremic geriatric patients. Int Urol Nephrol. 2014;46(8):1589–94. doi: 10.1007/s11255-014-0721-2.
    1. Bataille S, Baralla C, Torro D, et al. Undercorrection of hypernatremia is frequent and associated with mortality. BMC Nephrol. 2014;15(1):37. doi: 10.1186/1471-2369-15-37.
    1. Phillips PA, Rolls BJ, Ledingham JG, et al. Reduced thirst after water deprivation in healthy elderly men. N Engl J Med. 1984;311(12):753–9. doi: 10.1056/NEJM198409203111202.
    1. Rolls BJ, Phillips PA. Aging and disturbances of thirst and fluid balance. Nutr Rev. 1990;48(3):137–44. doi: 10.1111/j.1753-4887.1990.tb02915.x.
    1. AlZahrani A, Sinnert R, Gernsheimer J. Acute kidney injury, sodium disorders, and hypercalcemia in the aging kidney: diagnostic and therapeutic management strategies in emergency medicine. Clin Geriatr Med. 2013;29(1):275–319. doi: 10.1016/j.cger.2012.10.007.
    1. Rowe JW, Shock NW, DeFronzo RA. The influence of age on the renal response to water deprivation in man. Nephron. 1976;17(4):270–8. doi: 10.1159/000180731.
    1. Beck N, Yu BP. Effect of aging on urinary concentrating mechanism and vasopressin-dependent cAMP in rats. Am J Physiol. 1982;243(2):F121–5.
    1. Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med. 1987;83(5):905–8. doi: 10.1016/0002-9343(87)90649-8.
    1. Fenske W, Quinkler M, Lorenz D, et al. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome—revisiting the direct and indirect water deprivation tests. J Clin Endocrinol Metab. 2011;96(5):1506–15. doi: 10.1210/jc.2010-2345.
    1. Winzeler B, Zweifel C, Nigro N, et al. Postoperative copeptin concentration predicts diabetes insipidus after pituitary surgery. J Clin Endocrinol Metab. 2015;100(6):2275–82. doi: 10.1210/jc.2014-4527.
    1. Katan M, Fluri F, Morgenthaler NG, et al. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol. 2009;66(6):799–808. doi: 10.1002/ana.21783.
    1. Maisel A, Xue Y, Shah K, et al. Increased 90-day mortality in patients with acute heart failure with elevated copeptin: secondary results from the Biomarkers in Acute Heart Failure (BACH) study. Circ Heart Fail. 2011;4(5):613–20. doi: 10.1161/CIRCHEARTFAILURE.110.960096.
    1. Timper K, Fenske W, Kuhn F, et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. J Clin Endocrinol Metab. 2015;100(6):2268–74. doi: 10.1210/jc.2014-4507.
    1. Comtois R, Bertrand S, Beauregard H, Vinay P. Low serum urea level in dehydrated patients with central diabetes insipidus. CMAJ. 1988;139(10):965–9.
    1. Rocha AS, Kudo LH. Water, urea, sodium, chloride, and potassium transport in the in vitro isolated perfused papillary collecting duct. Kidney Int. 1982;22(5):485–91. doi: 10.1038/ki.1982.201.
    1. Kokko JP. The role of the collecting duct in urinary concentration. Kidney Int. 1987;31(2):606–10. doi: 10.1038/ki.1987.41.

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