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Bhattarai A, Shah S, Baidya S, Thapa R, Bhandari S, Tuladhar ET, Acharya SP, Sah R. Association of copeptin levels with patient prognosis and survival in sepsis syndromes: a meta-analysis. Int J Surg 2024; 110:2355-2365. [PMID: 38668663 PMCID: PMC11019991 DOI: 10.1097/js9.0000000000001069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 12/24/2023] [Indexed: 04/29/2024]
Abstract
BACKGROUND Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis. OBJECTIVE To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality. METHODS Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model. RESULTS Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81-2.16, P<0.0001), (SMD: 1.94, 95% CI: 0.34-3.54, P=0.02), and (SMD: 2.17, 95% CI: 0.68-3.66, P=0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: -1.73; 95% CI: -2.41 to -1.06, P<0.001). CONCLUSION AND RELEVANCE Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients' prognosis.
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Affiliation(s)
| | | | | | | | | | - Eans T. Tuladhar
- Department of Biochemistry, Institute of Medicine, Tribhuvan University
| | | | - Ranjit Sah
- Department of Microbiology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
- Department of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
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Gergics M, Pham-Dobor G, Kurdi C, Montskó G, Mihályi K, Bánfai G, Kanizsai P, Kőszegi T, Mezősi E, Bajnok L. Apelin-13 as a Potential Biomarker in Critical Illness. J Clin Med 2023; 12:4801. [PMID: 37510916 PMCID: PMC10381233 DOI: 10.3390/jcm12144801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/11/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND The adrenocortical system and copeptin as prognostic markers were intensively investigated in critical illness. The potential predictive power of apelin-13 as a biomarker is largely unknown. We aimed to investigate the prognostic role of apelin-13 in relation to free cortisol, aldosterone, CRH, and copeptin in critically ill patients. METHODS In this prospective observational study, 124 critically ill patients (64 men, 60 women, median age: 70 (59-78) years) were consecutively enrolled at the time of admission. All routinely available clinical and laboratory parameters were evaluated and correlated to hormonal changes. RESULTS Serum apelin-13 was 1161 (617-2967) pg/mL in non-survivors vs. 2477 (800-3531) pg/mL in survivors (p = 0.054). The concentrations of apelin-13 and CRH had strong positive correlations (r = 0.685, p < 0.001) and were significantly higher in surviving non-septic patients (Apelin-13 (pg/mL): 2286 (790-3330) vs. 818 (574-2732) p < 0.05; CRH (pg/mL) 201 (84-317) vs. 89 (74-233) p < 0.05). Apelin-13 and free cortisol were independent determinants of survival in the multivariate Cox regression analysis, while copeptin, CRH, or aldosterone were not. CONCLUSIONS Beyond free cortisol, serum apelin-13 may also help refine prognostic predictions in the early phase of critical illness, especially in non-septic patients.
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Affiliation(s)
- Marin Gergics
- 1st Department of Internal Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Gréta Pham-Dobor
- 1st Department of Internal Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Csilla Kurdi
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Gergely Montskó
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Krisztina Mihályi
- Department of Emergency Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Gábor Bánfai
- Department of Emergency Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Péter Kanizsai
- Department of Emergency Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Tamás Kőszegi
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Emese Mezősi
- 1st Department of Internal Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - László Bajnok
- 1st Department of Internal Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
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Abdelmageed M, Güzelgül F. Copeptin: Up-to-date diagnostic and prognostic role highlight. Anal Biochem 2023:115181. [PMID: 37247750 DOI: 10.1016/j.ab.2023.115181] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 05/03/2023] [Accepted: 05/04/2023] [Indexed: 05/31/2023]
Abstract
Arginine Vasopressin (AVP) is one of the key hormones in the human body. AVP is clinically important because it maintains body fluid balance and vascular tone. Unfortunately, AVP laboratory measurements are always difficult and with low accuracy. Copeptin, the C-terminal of the AVP precursor, is released in equal amounts with AVP, making it a sensitive marker of AVP release. Despite being a non-specific biomarker, copeptin earned a lot of attention as a novel biomarker due to easy and quick laboratory measurements. Recent studies have reported the critical role of copeptin as a clinical indicator, especially in the diagnosis and prognosis of many diseases. Besides, it was reported that the combination between copeptin and gold standard biomarkers improved the prognostic values of those biomarkers. In this review, the role of copeptin as a new predictive diagnostic and prognostic biomarker of various diseases is highlighted according to the most recent studies. In addition, the importance of using copeptin as a marker in different medical departments and the impact of this on improving healthcare service was discussed.
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Affiliation(s)
- Marwa Abdelmageed
- Tokat Gaziosmanpasa University, Faculty of Medicine, Department of Medical Biochemistry, Tokat City, Turkiye.
| | - Figen Güzelgül
- Tokat Gaziosmanpasa University, Faculty of Pharmacy, Department of Biochemistry, Tokat City, Turkiye.
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Saleh NY, Aboelghar HM, Garib MI, Rizk MS, Mahmoud AA. Pediatric sepsis diagnostic and prognostic biomarkers: pancreatic stone protein, copeptin, and apolipoprotein A-V. Pediatr Res 2023:10.1038/s41390-023-02499-0. [PMID: 36755189 PMCID: PMC10382317 DOI: 10.1038/s41390-023-02499-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 11/21/2022] [Accepted: 12/27/2022] [Indexed: 02/10/2023]
Abstract
BACKGROUND We assessed serum concentrations of pancreatic stone protein (PSP), copeptin, and apolipoprotein A-V (APOA5) biomarkers for the diagnosis and prognosis of pediatric sepsis, a condition associated with high mortality. METHODS This prospective study included 180 children admitted to the Pediatric Intensive Care Unit and 100 healthy controls at Menoufia University Hospital. Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality-2 (PIM2), and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated. Serum PSP, copeptin and APOA5 were measured once within 24 h of admission. RESULTS PSP, copeptin, and APOA5 were significantly higher in the patients than in the controls (p < 0.001). PSP and copeptin were increased among children who required mechanical ventilation (MV), had multiple organ dysfunctions, and were non-survivors, but APOA5 was decreased in those children. Logistic regression analyses showed that high pSOFA, high PSP and copeptin, low APOA5, and use of MV were associated with mortality. The receiver operating characteristic revealed that the area under the curve (AUC) for APOA5, copeptin, and PSP (0.965, 0.960, and 0.868, respectively) demonstrated high sensitivity (96%, 94%, and 80%) for sepsis diagnosis. The AUC values for PSP, copeptin, and APOA5 were 0.709, 0.705, and 0.571, respectively, with sensitivities of 74%, 58%, and 58% for mortality prediction. CONCLUSIONS PSP, copeptin, and APOA5 are promising diagnostic biomarkers for pediatric sepsis but inadequate predictors of mortality. IMPACT Apolipoprotein A-V (APOA5), copeptin, and pancreatic stone protein (PSP) are acute-phase proteins with diagnostic value in evaluating critically ill pediatric patients with sepsis and detecting sepsis severity. PSP and copeptin had the power to discriminate non-survivors from survivors. APOA5 was less powerful than the other biomarkers in discriminating between survivors and non-survivors.
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Affiliation(s)
- Nagwan Y Saleh
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt.
| | - Hesham M Aboelghar
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
| | - Mohamed I Garib
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
| | - Mohammed S Rizk
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
| | - Asmaa A Mahmoud
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
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5
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STANCIOIU F, IVANESCU B, DUMITRESCU R. Perspectives on the Immune System in Sepsis. MAEDICA 2022; 17:404-414. [PMID: 36032596 PMCID: PMC9375866 DOI: 10.26574/maedica.2022.17.2.395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Beyond the modifications shown by the biochemistry labs, profound and ample modifications are seen in septic patients at a molecular level stemming from DNA translation and gene expression, manifested as unique profiles of mRNA (messenger), as well as non-coding, functional RNAs: miRNA (micro) and lncRNAs (long non-coding). Counteracting these modifications requires treatment with pleiotropic molecules and/or combination of molecules and opens the possibility of future treatments with arrays of siRNAs and/or specific panels of small molecules tailored for each patient subpopulation.
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Affiliation(s)
| | | | - Radu DUMITRESCU
- University of Bucharest, Medicover Hospital, Bucharest, Romania
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Mu D, Ma C, Cheng J, Zou Y, Qiu L, Cheng X. Copeptin in fluid disorders and stress. Clin Chim Acta 2022; 529:46-60. [PMID: 35143773 DOI: 10.1016/j.cca.2022.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 12/16/2022]
Abstract
Copeptin, a glycosylated peptide of 39 amino acids, is the C-terminal segment of arginine vasopressin (AVP) precursor peptide, which is consisted of two other fragments, vasopressin and neurophysin Ⅱ. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis and regulation of the endocrine stress response. Numerous studies have demonstrated that the endogenous AVP in plasma is a meaningful biomarker to guide diagnosis and therapy of diseases associated with fluids disorders and stress. However, due to its instability, short half-time life in circulation and lack of readily available AVP assays, clinical measurement of AVP is restricted. In contrast to AVP, copeptin which is released in an equimolar mode with AVP from the pituitary, has emerged as a stable and simple-to-measure surrogate marker of AVP and displays excellent potential in diagnosis, differentiation and prognosis of various diseases. This review will discuss the studies on the clinical value of copeptin in different diseases, especially in AVP-dependent fluids disorders, as well as issues and prospects of the application of this potential biomarker.
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Affiliation(s)
- Danni Mu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Chaochao Ma
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Jin Cheng
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Yutong Zou
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Ling Qiu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xinqi Cheng
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China.
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Alba-Patiño A, Vaquer A, Barón E, Russell SM, Borges M, de la Rica R. Micro- and nanosensors for detecting blood pathogens and biomarkers at different points of sepsis care. Mikrochim Acta 2022; 189:74. [PMID: 35080669 PMCID: PMC8790942 DOI: 10.1007/s00604-022-05171-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 12/26/2021] [Indexed: 12/29/2022]
Abstract
Severe infections can cause a dysregulated response leading to organ dysfunction known as sepsis. Sepsis can be lethal if not identified and treated right away. This requires measuring biomarkers and pathogens rapidly at the different points where sepsis care is provided. Current commercial approaches for sepsis diagnosis are not fast, sensitive, and/or specific enough for meeting this medical challenge. In this article, we review recent advances in the development of diagnostic tools for sepsis management based on micro- and nanostructured materials. We start with a brief introduction to the most popular biomarkers for sepsis diagnosis (lactate, procalcitonin, cytokines, C-reactive protein, and other emerging protein and non-protein biomarkers including miRNAs and cell-based assays) and methods for detecting bacteremia. We then highlight the role of nano- and microstructured materials in developing biosensors for detecting them taking into consideration the particular needs of every point of sepsis care (e.g., ultrafast detection of multiple protein biomarkers for diagnosing in triage, emergency room, ward, and intensive care unit; quantitative detection to de-escalate treatment; ultrasensitive and culture-independent detection of blood pathogens for personalized antimicrobial therapies; robust, portable, and web-connected biomarker tests outside the hospital). We conclude with an overview of the most utilized nano- and microstructured materials used thus far for solving issues related to sepsis diagnosis and point to new challenges for future development.
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Affiliation(s)
- Alejandra Alba-Patiño
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
- Department of Chemistry, University of the Balearic Islands, Palma, Spain
| | - Andreu Vaquer
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
- Department of Chemistry, University of the Balearic Islands, Palma, Spain
| | - Enrique Barón
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
| | - Steven M Russell
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Marcio Borges
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
- Multidisciplinary Sepsis Unit, ICU, Son Llàtzer University Hospital, Palma, Spain
| | - Roberto de la Rica
- Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
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8
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Velissaris D, Zareifopoulos N, Karamouzos V, Karanikolas E, Pierrakos C, Koniari I, Karanikolas M. Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis. Cureus 2021; 13:e15019. [PMID: 34150378 PMCID: PMC8202808 DOI: 10.7759/cureus.15019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited by year of publication so all articles archived in the database would be retrieved. No article from before 2010 was identified. A total of 57 publications of the last decade were included, all of which support the use of presepsin as a biomarker for the assessment of septic patients. It has been used alone or in combination with commonly used biomarkers in the evaluation of patients with sepsis in settings such as the emergency department and the intensive care unit. It is useful in the initial workup of patients with suspected sepsis in the emergency setting and may be a predictive factor of mortality and the most severe complication of sepsis. Presepsin seems to be a valuable tool for the laboratory workup of sepsis, especially when used in conjunction with other biomarkers and clinical rating scores with an established role in this population. Further research is needed to evaluate the clinical implications of utilizing presepsin measurements in the workup of sepsis.
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Affiliation(s)
- Dimitrios Velissaris
- Department of Internal Medicine, General University Hospital of Patras, Patras, GRC
| | - Nicholas Zareifopoulos
- Department of Psychiatry, General Hospital of Nikaia, Piraeus "Agios Panteleimon", Athens, GRC.,Department of Internal Medicine, University of Patras School of Health Sciences, Patras, GRC
| | | | | | - Charalampos Pierrakos
- Intensive Care Unit, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, BEL
| | - Ioanna Koniari
- Department of Electrophysiology and Device, University Hospital of South Manchester NHS Foundation Trust, Manchester, GBR
| | - Menelaos Karanikolas
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA
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Gregoriano C, Molitor A, Haag E, Kutz A, Koch D, Haubitz S, Conen A, Bernasconi L, Hammerer-Lercher A, Fux CA, Mueller B, Schuetz P. Activation of Vasopressin System During COVID-19 is Associated With Adverse Clinical Outcomes: An Observational Study. J Endocr Soc 2021; 5:bvab045. [PMID: 34056499 PMCID: PMC7989362 DOI: 10.1210/jendso/bvab045] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Indexed: 12/26/2022] Open
Abstract
Background Activation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular, and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured levels of copeptin on admission and after days 3/4, 5/6, and 7/8 in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and acute or chronic bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. Results Median admission copeptin levels in COVID-19 patients were almost 4-fold higher in nonsurvivors compared with survivors (49.4 pmol/L [iterquartile range (IQR) 24.9–68.9 pmol/L] vs 13.5 pmol/L [IQR 7.0–26.7 pmol/L]), resulting in an age- and gender-adjusted odds ratio of 7.0 (95% confidence interval [CI] 1.2–40.3), p < 0.03 for mortality. Higher copeptin levels in nonsurvivors persisted during the short-term follow-up. Compared with the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels. Conclusions A pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections.
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Affiliation(s)
- Claudia Gregoriano
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Alexandra Molitor
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Ellen Haag
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Alexander Kutz
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Daniel Koch
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Sebastian Haubitz
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Department of Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Anna Conen
- Department of Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Medical Faculty, University of Basel, 4056 Basel, Switzerland
| | - Luca Bernasconi
- Institute of Laboratory Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | | | - Christoph A Fux
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Department of Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Beat Mueller
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Medical Faculty, University of Basel, 4056 Basel, Switzerland
| | - Philipp Schuetz
- Medical University Department of Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Medical Faculty, University of Basel, 4056 Basel, Switzerland
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10
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Gomes DA, de Almeida Beltrão RL, de Oliveira Junior FM, da Silva Junior JC, de Arruda EPC, Lira EC, da Rocha MJA. Vasopressin and copeptin release during sepsis and septic shock. Peptides 2021; 136:170437. [PMID: 33181268 DOI: 10.1016/j.peptides.2020.170437] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 10/23/2020] [Accepted: 10/26/2020] [Indexed: 12/22/2022]
Abstract
Sepsis is defined as a potentially fatal organ dysfunction caused by a dysregulated host response to infection. Despite tremendous progress in the medical sciences, sepsis remains one of the leading causes of morbidity and mortality worldwide. The host response to sepsis and septic shock involves changes in the immune, autonomic, and neuroendocrine systems. Regarding neuroendocrine changes, studies show an increase in plasma vasopressin (AVP) concentrations followed by a decline, which may be correlated with septic shock. AVP is a peptide hormone derived from a larger precursor (preprohormone), along with two peptides, neurophysin II and copeptin. AVP is synthesized in the hypothalamus, stored and released from the neurohypophysis into the bloodstream by a wide range of stimuli. The measurement of AVP has limitations due to its plasma instability and short half-life. Copeptin is a more stable peptide than AVP, and its immunoassay is feasible. The blood concentrations of copeptin mirror those of AVP in many physiological states; paradoxically, during sepsis-related organ dysfunction, an uncoupling between copeptin and AVP blood levels appears to happen. In this review, we focus on clinical and experimental studies that analyzed AVP and copeptin blood concentrations over time in sepsis. The findings suggest that AVP and copeptin behave similarly in the early stages of sepsis; however, we did not find a proportional decrease in copeptin concentrations as seen with AVP during septic shock. Copeptin levels were higher in nonsurvivors than in survivors, suggesting that copeptin may work as a marker of severity or sepsis-related organ dysfunction.
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Affiliation(s)
- Dayane Aparecida Gomes
- Department of Physiology and Pharmacology, Bioscience Center, Federal University of Pernambuco, Brazil.
| | | | | | | | | | - Eduardo Carvalho Lira
- Department of Physiology and Pharmacology, Bioscience Center, Federal University of Pernambuco, Brazil
| | - Maria José Alves da Rocha
- Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Brazil
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11
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Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent JL. Biomarkers of sepsis: time for a reappraisal. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2020; 24:287. [PMID: 32503670 PMCID: PMC7273821 DOI: 10.1186/s13054-020-02993-5] [Citation(s) in RCA: 321] [Impact Index Per Article: 64.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 05/14/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. METHODS Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included. RESULTS We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. CONCLUSIONS The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
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Affiliation(s)
- Charalampos Pierrakos
- Intensive Care Department, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | | | - Max Bisdorff
- Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium
| | - John C Marshall
- Surgery/Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
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12
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Salvo F, Luppi F, Lucchesi DM, Canovi S, Franchini S, Polese A, Santi F, Trabucco L, Fasano T, Ferrari AM. Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients. BMC Emerg Med 2020; 20:14. [PMID: 32093639 PMCID: PMC7041089 DOI: 10.1186/s12873-020-00310-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 02/11/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. METHODS This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. RESULTS One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 (P 0.0015), and in predicting hospital admission (P 0.0002) and blood transfusion (P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. CONCLUSIONS In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.
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Affiliation(s)
- Fulvio Salvo
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy. .,Present address: Respiratory and Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
| | - Francesco Luppi
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Davide M Lucchesi
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Simone Canovi
- Clinical Chemistry and Endocrinology Laboratory, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Stefano Franchini
- Emergency Department, Ospedale San Raffaele, via Olgettina 60, 20132, Milan, Italy
| | - Alessandra Polese
- Clinical Chemistry and Endocrinology Laboratory, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Francesca Santi
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Laura Trabucco
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Tommaso Fasano
- Clinical Chemistry and Endocrinology Laboratory, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
| | - Anna Maria Ferrari
- Department of Emergency Medicine Azienda USL-IRCCS di Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy
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Gille J, Schmidt J, Kremer T, Sablotzki A. Evaluation of MR-proANP and copeptin for sepsis diagnosis after burn injury. J Crit Care 2019; 52:149-155. [DOI: 10.1016/j.jcrc.2019.04.031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 04/11/2019] [Accepted: 04/29/2019] [Indexed: 01/02/2023]
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Schneider C, Remmler J, Netto J, Seehofer D, Engelmann C, Berg T, Thiery J, Kaiser T. Copeptin – a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease. ACTA ACUST UNITED AC 2019; 57:1897-1905. [DOI: 10.1515/cclm-2019-0023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 05/09/2019] [Indexed: 12/29/2022]
Abstract
Abstract
Background
For many patients with end-stage liver disease, liver transplantation represents the only curative therapy. Transplant recipients are scored and ranked using the model for end-stage liver disease (MELD/MELD-Na). Circulatory impairment is known to deteriorate outcomes; however, it is not incorporated into the current allocation system’s score. The aim of our study is to analyze the predictive value of copeptin as a biomarker of circulatory impairment and increased short-term mortality risk in patients with end-stage liver disease.
Methods
We conducted a retrospective observational study of 615 patients with end-stage liver disease. Patients were recruited using assessments performed during the evaluation process for liver transplantation. Copeptin values were analyzed in comparison to MELD-Na, interleukin 6 (IL-6), and C-reactive protein (CRP).
Results
Elevated levels of copeptin, IL-6 and CRP, as well as high MELD-Na scores, were significantly correlated with mortality. In a comparison of copeptin-tertiles, patients in group T3 (16.3 pmol/L or more) showed a significantly higher mortality risk (hazard ratio 11.2, p < 0.001). After adjusting for MELD-Na, copeptin remains an independent predictor of mortality. It shows its greatest prognostic strength in short-term mortality, where it performs comparable to MELD-Na (AUROC for 7 day-mortality, 0.941/0.939; p = 0.981) and shows an additional predictive value to MELD-Na for short-term mortality (7 days, p: 0.046; 30 days, p: 0.006).
Conclusions
Copeptin presents a valuable individual biomarker in detecting patients at risk for short-term mortality. Further studies should be performed to confirm our findings.
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Affiliation(s)
- Christoph Schneider
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany
| | - Johannes Remmler
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany
| | - Jeffrey Netto
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany
| | - Daniel Seehofer
- Department of Visceral, Transplant, Thoracic and Vascular, Surgery , University Hospital Leipzig , Leipzig , Germany
| | - Cornelius Engelmann
- Section of Hepatology, Clinic for Gastroenterology , University Clinic Leipzig , Leipzig , Germany
| | - Thomas Berg
- Section of Hepatology, Clinic for Gastroenterology , University Clinic Leipzig , Leipzig , Germany
| | - Joachim Thiery
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany
| | - Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany
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Largeau B, Le Tilly O, Sautenet B, Salmon Gandonnière C, Barin-Le Guellec C, Ehrmann S. Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link? Mol Neurobiol 2019; 56:6792-6806. [PMID: 30924075 DOI: 10.1007/s12035-019-1553-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 03/13/2019] [Indexed: 12/12/2022]
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by a typical brain edema. Its pathogenesis is still debated through hypoperfusion and hyperperfusion theories, which have many limitations. As PRES occurs almost exclusively in clinical situations with arginine vasopressin (AVP) hypersecretion, such as eclampsia and sepsis, we hypothesize that AVP plays a central pathophysiologic role. In this review, we discuss the genesis of PRES and its symptoms through this novel approach. We theorize that AVP axis stimulation precipitates PRES development through an increase in AVP secretion or AVP receptor density. Activation of vasopressin V1a receptors leads to cerebral vasoconstriction, causing endothelial dysfunction and cerebral ischemia. This promotes cytotoxic edema through hydromineral transglial flux dysfunction and may increase endothelial permeability, leading to subsequent vasogenic brain edema. If our hypothesis is confirmed, it opens new perspectives for better patient monitoring and therapies targeting the AVP axis in PRES.
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Affiliation(s)
- Bérenger Largeau
- CHRU de Tours, Laboratoire de Biochimie et Biologie Moléculaire, Tours, France.
| | - Olivier Le Tilly
- CHRU de Tours, Laboratoire de Biochimie et Biologie Moléculaire, Tours, France
| | - Bénédicte Sautenet
- Université de Tours, Université de Nantes, INSERM, Methods in patients-centered outcomes and health research (SPHERE) - UMR 1246, CHRU de Tours, Service de Néphrologie-Hypertension artérielle, Dialyses et Transplantation Rénale, Tours, France
| | | | - Chantal Barin-Le Guellec
- Université de Tours, Université de Limoges, INSERM, Individual profiling and prevention of risks with immunosuppressive therapies and transplantation (IPPRITT) - UMR 1248, CHRU de Tours, Laboratoire de Biochimie et Biologie Moléculaire, Tours, France
| | - Stephan Ehrmann
- Université de Tours, INSERM, Centre d'étude des pathologies respiratoires (CEPR) - UMR 1100, CHRU de Tours, Service de Médecine Intensive Réanimation, CIC 1415, réseau CRICS-TRIGGERSEP, Tours, France
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16
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Morello F, Oddi M, Cavalot G, Ianniello A, Giachino F, Nazerian P, Battista S, Magnino C, Tizzani M, Settanni F, Mengozzi G, Lupia E. Prospective diagnostic and prognostic study of copeptin in suspected acute aortic syndromes. Sci Rep 2018; 8:16713. [PMID: 30425269 PMCID: PMC6233166 DOI: 10.1038/s41598-018-35016-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 10/03/2018] [Indexed: 01/16/2023] Open
Abstract
Acute aortic syndromes (AAS) are cardiovascular emergencies with unmet diagnostic needs. Copeptin is released upon stress conditions and is approved for rule-out of myocardial infarction (MI). As MI and AAS share presenting symptoms, stress mechanisms and necessity for rapid diagnosis, copeptin appears as an attractive biomarker also for AAS. We thus performed a diagnostic and observational study in Emergency Department (ED) outpatients. Inclusion criteria were chest/abdominal/back pain, syncope and/or perfusion deficit, plus AAS in differential diagnosis. Blood samples were obtained in the ED. 313 patients were analyzed and 105 (33.5%) were diagnosed with AAS. Median copeptin was 38.91 pmol/L (interquartile range, IQR, 16.33-173.4) in AAS and 7.51 pmol/L (IQR 3.58-15.08) in alternative diagnoses (P < 0.001). Copeptin (≥10 pmol/L) had a sensitivity of 80.8% (95% confidence interval, CI, 72.2-87.2) and a specificity of 63.6% (CI 56.9-69.9) for AAS. Within 6 hours, the sensitivity and specificity were 88.7% (CI 79.3-94.2) and 52.4% (CI 42.9-61.8) respectively. Combination with D-dimer did not increase the diagnostic yield. Furthermore, copeptin ≥25 pmol/L predicted mortality in patients with alternative diagnoses but not with AAS. In conclusion, copeptin increases in most patients with AAS within the first hours, but the accuracy of copeptin for diagnosis AAS is suboptimal.
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Affiliation(s)
- Fulvio Morello
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy.
| | - Matteo Oddi
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Giulia Cavalot
- S.C.U. Medicina Interna 2, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Alice Ianniello
- S.C. Biochimica Clinica, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Francesca Giachino
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | | | - Stefania Battista
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Corrado Magnino
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Maria Tizzani
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Fabio Settanni
- S.C. Biochimica Clinica, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Giulio Mengozzi
- S.C. Biochimica Clinica, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
| | - Enrico Lupia
- S.C.U. Medicina d'Urgenza, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Torino, Italy
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Tasneem M, Mannix C, Wong A, Zhang J, Rangan G. Is serum copeptin a modifiable biomarker in autosomal dominant polycystic kidney disease? World J Nephrol 2018; 7:51-57. [PMID: 29527508 PMCID: PMC5838414 DOI: 10.5527/wjn.v7.i2.51] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 01/29/2018] [Accepted: 02/28/2018] [Indexed: 02/06/2023] Open
Abstract
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]. However, serum copeptin is strongly correlated with creatinine, and its additional value as a prognostic biomarker over estimated glomerular filtration rate and TKV is not certain. It has also been suggested that copeptin could be a predictive biomarker to select ADPKD patients who are most likely to benefit from AVP-modifying therapies, but prospective data to validate this assumption are required. In this regard, long-term randomised clinical trials evaluating the effect of prescribed water intake on renal cyst growth may contribute to addressing this hypothesis. In conclusion, although serum copeptin is aligned with the basic pathogenesis of ADPKD, further rigorous studies are needed to define if it will contribute to enabling the delivery of personalised care in ADPKD.
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Affiliation(s)
- Moomal Tasneem
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Carly Mannix
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Annette Wong
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Jennifer Zhang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Gopala Rangan
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
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18
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The Circadian Rhythm of Copeptin, the C-Terminal Portion of Arginine Vasopressin. J Biomark 2017; 2017:4737082. [PMID: 28656120 PMCID: PMC5471567 DOI: 10.1155/2017/4737082] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 05/02/2017] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Several studies have investigated copeptin as a prognostic marker of different acute diseases and as a diagnostic marker in disorders of water and salt homeostasis. However, no data of the normal circadian rhythm of copeptin in healthy subjects are available. AIM To investigate the circadian rhythm of copeptin in healthy subjects under standardized conditions. METHODS 19 healthy volunteers aged 18 to 53 years, male and female, were studied in a prospective observational study. In all 19 participants, blood samples for copeptin were taken in regular intervals of 30 minutes for 24 hours after a fasting period of minimum 8 hours. RESULTS The mean values of copeptin showed a circadian rhythm, similar to that described for AVP release, with a trend towards higher levels (5.9 ± 1 pmol/L) at night and early morning between 4 am and 6 am and lowest levels (2.3 ± 0.2 pmol/L) in the late afternoon between 5 pm and 7 pm. This finding was only observed in individuals with initial higher copeptin levels, whereas in individuals with lower basal copeptin levels no circadian rhythm was observed. CONCLUSION There is evidence for a circadian rhythm in copeptin release during 24 hours, however, of minor extent. These findings suggest that copeptin levels can be determined irrespectively of the time of the day.
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Liu Y, Hou JH, Li Q, Chen KJ, Wang SN, Wang JM. Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis. SPRINGERPLUS 2016; 5:2091. [PMID: 28028489 PMCID: PMC5153391 DOI: 10.1186/s40064-016-3591-5] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Accepted: 10/20/2016] [Indexed: 12/25/2022]
Abstract
Background Sepsis is one of the most common diseases that seriously threaten human health. Although a large number of markers related to sepsis have been reported in the last two decades, the diagnostic accuracy of these biomarkers remains unclear due to the lack of similar baselines among studies. Therefore, we conducted a large systematic review and meta-analysis to evaluate the diagnostic value of biomarkers from studies that included non-infectious systemic inflammatory response syndrome patients as a control group. Methods We searched Medline, Embase and the reference lists of identified studies beginning in April 2014. The last retrieval was updated in September 2016. Results Ultimately, 86 articles fulfilled the inclusion criteria. Sixty biomarkers and 10,438 subjects entered the final analysis. The areas under the receiver operating characteristic curves for the 7 most common biomarkers, including procalcitonin, C-reactive protein, interleukin 6, soluble triggering receptor expressed on myeloid cells-1, presepsin, lipopolysaccharide binding protein and CD64, were 0.85, 0.77, 0.79, 0.85, 0.88, 0.71 and 0.96, respectively. The remaining 53 biomarkers exhibited obvious variances in diagnostic value and methodological quality. Conclusions Although some biomarkers displayed moderate or above moderate diagnostic value for sepsis, the limitations of the methodological quality and sample size may weaken these findings. Currently, we still lack an ideal biomarker to aid in the diagnosis of sepsis. In the future, biomarkers with better diagnostic value as well as a combined diagnosis using multiple biomarkers are expected to solve the challenge of the diagnosis of sepsis. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-3591-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yong Liu
- Intensive Care Unit, Suining Central Hospital, Deshengxi Road 127, Chuanshan District, Suining, 629000 Sichuan People's Republic of China
| | - Jun-Huan Hou
- Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042 People's Republic of China.,State Key Laboratory of Trauma, Burn and Combined Injury, Trauma Center, Chongqing, 400042 People's Republic of China
| | - Qing Li
- Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042 People's Republic of China.,State Key Laboratory of Trauma, Burn and Combined Injury, Trauma Center, Chongqing, 400042 People's Republic of China
| | - Kui-Jun Chen
- Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042 People's Republic of China.,State Key Laboratory of Trauma, Burn and Combined Injury, Trauma Center, Chongqing, 400042 People's Republic of China
| | - Shu-Nan Wang
- Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Jian-Min Wang
- Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042 People's Republic of China.,State Key Laboratory of Trauma, Burn and Combined Injury, Trauma Center, Chongqing, 400042 People's Republic of China
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