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Published in: Critical Care 1/2020

01-12-2020 | Acute Kidney Injury | Research

Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients

Authors: François Dépret, Juliette Amzallag, Adrien Pollina, Laure Fayolle-Pivot, Maxime Coutrot, Maïté Chaussard, Karine Santos, Oliver Hartmann, Marion Jully, Alexandre Fratani, Haikel Oueslati, Alexandru Cupaciu, Mourad Benyamina, Lucie Guillemet, Benjamin Deniau, Alexandre Mebazaa, Etienne Gayat, Boris Farny, Julien Textoris, Matthieu Legrand, for the PRONOBURN group

Published in: Critical Care | Issue 1/2020

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Abstract

Background

Dipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients.

Methods

In this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI).

Results

One hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5–63) years, with a median total body surface area burned of 35% (25–53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7–11). Ninety-day mortality was 32%. The median DPP3admin was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8–103.5] versus 27.1 ng/mL [IQR 19.4–38.9]; p < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3admin but decreased levels on day 3. Patients with circulatory failure had higher DPP3admin (39.2 ng/mL [IQR 25.9–76.1] versus 28.4 ng/mL [IQR 19.8–39.6]; p = 0.001) as well as patients with AKI (49.7 ng/mL [IQR 30.3–87.3] versus 27.6 ng/mL [IQR 19.4–41.4]; p = 0.001). DPP3admin added prognostic value on top of ABSI (added chi2 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi2 4.9, p = 0.0268), and plasma lactate at admission (added chi2 6.9, p = 0.0086) to predict circulatory failure within the first 48 h.

Conclusions

Plasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.
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Literature
1.
go back to reference Soussi S, Dépret F, Benyamina M, Legrand M. Early hemodynamic management of critically ill burn patients. Anesthesiology. 2018;129:583–9.CrossRef Soussi S, Dépret F, Benyamina M, Legrand M. Early hemodynamic management of critically ill burn patients. Anesthesiology. 2018;129:583–9.CrossRef
2.
go back to reference Soussi S, Deniau B, Ferry A, Levé C, Benyamina M, Maurel V, et al. Low cardiac index and stroke volume on admission are associated with poor outcome in critically ill burn patients: a retrospective cohort study. Ann Intensive Care. 2016;6:87.CrossRef Soussi S, Deniau B, Ferry A, Levé C, Benyamina M, Maurel V, et al. Low cardiac index and stroke volume on admission are associated with poor outcome in critically ill burn patients: a retrospective cohort study. Ann Intensive Care. 2016;6:87.CrossRef
3.
go back to reference Soussi S, Taccori M, De Tymowski C, Depret F, Chaussard M, Fratani A, et al. Risk factors for acute mesenteric ischemia in critically ill burns patients—a matched case–control study. Shock. 2019;51:153–60.CrossRef Soussi S, Taccori M, De Tymowski C, Depret F, Chaussard M, Fratani A, et al. Risk factors for acute mesenteric ischemia in critically ill burns patients—a matched case–control study. Shock. 2019;51:153–60.CrossRef
4.
go back to reference Bak Z, Sjöberg F, Eriksson O, Steinvall I, Janerot-Sjoberg B. Cardiac dysfunction after burns. Burns. 2008;34:603–9.CrossRef Bak Z, Sjöberg F, Eriksson O, Steinvall I, Janerot-Sjoberg B. Cardiac dysfunction after burns. Burns. 2008;34:603–9.CrossRef
5.
go back to reference Zhan H, Yamamoto Y, Shumiya S, Kunimatsu M, Nishi K, Ohkubo I, et al. Peptidases play an important role in cataractogenesis: an immunohistochemical study on lenses derived from Shumiya cataract rats. Histochem J. 2001;33:511–21.CrossRef Zhan H, Yamamoto Y, Shumiya S, Kunimatsu M, Nishi K, Ohkubo I, et al. Peptidases play an important role in cataractogenesis: an immunohistochemical study on lenses derived from Shumiya cataract rats. Histochem J. 2001;33:511–21.CrossRef
6.
go back to reference Prajapati SC, Chauhan SS. Dipeptidyl peptidase III: a multifaceted oligopeptide N-end cutter: dipeptidyl peptidase III. FEBS J. 2011;278:3256–76.CrossRef Prajapati SC, Chauhan SS. Dipeptidyl peptidase III: a multifaceted oligopeptide N-end cutter: dipeptidyl peptidase III. FEBS J. 2011;278:3256–76.CrossRef
7.
go back to reference Pang X, Shimizu A, Kurita S, Zankov DP, Takeuchi K, Yasuda-Yamahara M, et al. Novel therapeutic role for dipeptidyl peptidase III in the treatment of hypertension. Hypertension. 2016;68:630–41.CrossRef Pang X, Shimizu A, Kurita S, Zankov DP, Takeuchi K, Yasuda-Yamahara M, et al. Novel therapeutic role for dipeptidyl peptidase III in the treatment of hypertension. Hypertension. 2016;68:630–41.CrossRef
9.
go back to reference Tobiasen J, Hiebert JM, Edlich RF. The abbreviated burn severity index. Ann Emerg Med. 1982;11:260–2.CrossRef Tobiasen J, Hiebert JM, Edlich RF. The abbreviated burn severity index. Ann Emerg Med. 1982;11:260–2.CrossRef
10.
go back to reference Bull JP, Squire JR. A study of mortality in a burns unit: standards for the evaluation of alternative methods of treatment. Ann Surg. 1949;130:160.CrossRef Bull JP, Squire JR. A study of mortality in a burns unit: standards for the evaluation of alternative methods of treatment. Ann Surg. 1949;130:160.CrossRef
11.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.CrossRef Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.CrossRef
13.
go back to reference Rich S, Sheikh A, Gallastegui J, Kondos GT, Mason T, Lam W. Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography. Am Heart J. 1982;104:603–6.CrossRef Rich S, Sheikh A, Gallastegui J, Kondos GT, Mason T, Lam W. Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography. Am Heart J. 1982;104:603–6.CrossRef
14.
go back to reference Kellum JA, Lameire N, For the KDIGO AKI guideline work group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Crit Care. 2013;17:204.CrossRef Kellum JA, Lameire N, For the KDIGO AKI guideline work group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Crit Care. 2013;17:204.CrossRef
15.
go back to reference Rehfeld L, Funk E, Jha S, Macheroux P, Melander O, Bergmann A. Novel methods for the quantification of dipeptidyl peptidase 3 (DPP3) concentration and activity in human blood samples. J Appl Lab Med. 2019;3:943–53.CrossRef Rehfeld L, Funk E, Jha S, Macheroux P, Melander O, Bergmann A. Novel methods for the quantification of dipeptidyl peptidase 3 (DPP3) concentration and activity in human blood samples. J Appl Lab Med. 2019;3:943–53.CrossRef
16.
17.
go back to reference Jeschke MG, Pinto R, Kraft R, Nathens AB, Finnerty CC, Gamelli RL, et al. Morbidity and survival probability in burn patients in modern burn care. Crit Care Med. 2015;43:808–15.CrossRef Jeschke MG, Pinto R, Kraft R, Nathens AB, Finnerty CC, Gamelli RL, et al. Morbidity and survival probability in burn patients in modern burn care. Crit Care Med. 2015;43:808–15.CrossRef
18.
go back to reference Legrand M, Guttormsen AB, Berger MM. Ten tips for managing critically ill burn patients: follow the RASTAFARI! Intensive Care Med. 2015;41:1107–9.CrossRef Legrand M, Guttormsen AB, Berger MM. Ten tips for managing critically ill burn patients: follow the RASTAFARI! Intensive Care Med. 2015;41:1107–9.CrossRef
19.
go back to reference Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet Lond Engl. 2019;394:1949–64.CrossRef Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet Lond Engl. 2019;394:1949–64.CrossRef
20.
go back to reference Wong BT, Chan MJ, Glassford NJ, Mårtensson J, Bion V, Chai SY, et al. Mean arterial pressure and mean perfusion pressure deficit in septic acute kidney injury. J Crit Care. 2015;30:975–81.CrossRef Wong BT, Chan MJ, Glassford NJ, Mårtensson J, Bion V, Chai SY, et al. Mean arterial pressure and mean perfusion pressure deficit in septic acute kidney injury. J Crit Care. 2015;30:975–81.CrossRef
21.
go back to reference Deniau B, Rehfeld L, Santos K, Dienelt A, Azibani F, Sadoune M, Kounde PR, Samuel JL, Tolpannen H, Lassus J, Harjola VP, Vodovar N, Bergmann A, Hartmann O, Mebazaa A, Blet A. Eur J Heart Fail. 2020;22(2):290–9. https://doi.org/10.1002/ejhf.1601. Deniau B, Rehfeld L, Santos K, Dienelt A, Azibani F, Sadoune M, Kounde PR, Samuel JL, Tolpannen H, Lassus J, Harjola VP, Vodovar N, Bergmann A, Hartmann O, Mebazaa A, Blet A. Eur J Heart Fail. 2020;22(2):290–9. https://​doi.​org/​10.​1002/​ejhf.​1601.
23.
go back to reference Chow JH, Abuelkasem E, Sankova S, Henderson RA, Mazzeffi MA, Tanaka KA. Reversal of vasodilatory shock: current perspectives on conventional, rescue, and emerging vasoactive agents for the treatment of shock. Anesth Analg. 2020;130:15–30.CrossRef Chow JH, Abuelkasem E, Sankova S, Henderson RA, Mazzeffi MA, Tanaka KA. Reversal of vasodilatory shock: current perspectives on conventional, rescue, and emerging vasoactive agents for the treatment of shock. Anesth Analg. 2020;130:15–30.CrossRef
24.
go back to reference Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419–30.CrossRef Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419–30.CrossRef
25.
go back to reference Wakefield BJ, Sacha GL, Khanna AK. Vasodilatory shock in the ICU and the role of angiotensin II. Curr Opin Crit Care. 2018;24:277–85.CrossRef Wakefield BJ, Sacha GL, Khanna AK. Vasodilatory shock in the ICU and the role of angiotensin II. Curr Opin Crit Care. 2018;24:277–85.CrossRef
Metadata
Title
Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients
Authors
François Dépret
Juliette Amzallag
Adrien Pollina
Laure Fayolle-Pivot
Maxime Coutrot
Maïté Chaussard
Karine Santos
Oliver Hartmann
Marion Jully
Alexandre Fratani
Haikel Oueslati
Alexandru Cupaciu
Mourad Benyamina
Lucie Guillemet
Benjamin Deniau
Alexandre Mebazaa
Etienne Gayat
Boris Farny
Julien Textoris
Matthieu Legrand
for the PRONOBURN group
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-02888-5

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