Skip to main content
Top
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

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

Authors: 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

Published in: Critical Care | Issue 1/2018

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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.CrossRef 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.CrossRef
2.
go back to reference 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.CrossRef 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.CrossRef
3.
4.
go back to reference Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124(2):197–203.CrossRef Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124(2):197–203.CrossRef
5.
go back to reference Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients: a heterogeneous, morbid, and iatrogenic entity. Ann Intern Med. 1987;107(3):309–19.CrossRef Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients: a heterogeneous, morbid, and iatrogenic entity. Ann Intern Med. 1987;107(3):309–19.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference Morgenthaler NG, Struck J, Jochberger S, Dunser MW. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab. 2008;19(2):43–9.CrossRef Morgenthaler NG, Struck J, Jochberger S, Dunser MW. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab. 2008;19(2):43–9.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract. 2012;120(4):c179–84. Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract. 2012;120(4):c179–84.
19.
go back to reference 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). 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).
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference Bataille S, Baralla C, Torro D, et al. Undercorrection of hypernatremia is frequent and associated with mortality. BMC Nephrol. 2014;15(1):37.CrossRef Bataille S, Baralla C, Torro D, et al. Undercorrection of hypernatremia is frequent and associated with mortality. BMC Nephrol. 2014;15(1):37.CrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference Rolls BJ, Phillips PA. Aging and disturbances of thirst and fluid balance. Nutr Rev. 1990;48(3):137–44.CrossRef Rolls BJ, Phillips PA. Aging and disturbances of thirst and fluid balance. Nutr Rev. 1990;48(3):137–44.CrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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.PubMed 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.PubMed
28.
go back to reference Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med. 1987;83(5):905–8.CrossRef Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med. 1987;83(5):905–8.CrossRef
29.
go back to reference 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.CrossRef 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.CrossRef
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.CrossRef 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.CrossRef
32.
go back to reference 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.CrossRef 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.CrossRef
33.
go back to reference 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.CrossRef 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.CrossRef
34.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
35.
go back to reference 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.CrossRef 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.CrossRef
36.
go back to reference Kokko JP. The role of the collecting duct in urinary concentration. Kidney Int. 1987;31(2):606–10.CrossRef Kokko JP. The role of the collecting duct in urinary concentration. Kidney Int. 1987;31(2):606–10.CrossRef
Metadata
Title
Copeptin levels and commonly used laboratory parameters in hospitalised patients with severe hypernatraemia - the “Co-MED study”
Authors
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
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-1955-7

Other articles of this Issue 1/2018

Critical Care 1/2018 Go to the issue