Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

Alexa Hollinger, Xavier Wittebole, Bruno François, Peter Pickkers, Massimo Antonelli, Etienne Gayat, Benjamin Glen Chousterman, Jean Baptiste Lascarrou, Thierry Dugernier, Salvatore Di Somma, Joachim Struck, Andreas Bergmann, Albertus Beishuizen, Jean Michel Constatin, Charles Damoisel, Nicolas Deye, Stéphane Gaudry, Vincent Huberlant, Gernot Marx, Emanuelle MercierHaikel Oueslati, Oliver Hartmann, Romain Sonneville, Pierre François Laterre, Alexandre Mebazaa, Matthieu Legrand

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients.

Original languageEnglish
Pages (from-to)1424-1433
Number of pages10
JournalKidney International Reports
Volume3
Issue number6
DOIs
Publication statusPublished - Nov 1 2018

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Septic Shock
Acute Kidney Injury
Sepsis
Biomarkers
Kidney
Intensive Care Units
Confidence Intervals
proenkephalin
Adrenomedullin
Renal Replacement Therapy
Mortality
Luminescence
Critical Illness
Observational Studies
Registries
Shock
Creatinine
Odds Ratio

Keywords

  • acute kidney injury
  • biomarker
  • diagnosis
  • sepsis

ASJC Scopus subject areas

  • Nephrology

Cite this

Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury : The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. / Hollinger, Alexa; Wittebole, Xavier; François, Bruno; Pickkers, Peter; Antonelli, Massimo; Gayat, Etienne; Chousterman, Benjamin Glen; Lascarrou, Jean Baptiste; Dugernier, Thierry; Di Somma, Salvatore; Struck, Joachim; Bergmann, Andreas; Beishuizen, Albertus; Constatin, Jean Michel; Damoisel, Charles; Deye, Nicolas; Gaudry, Stéphane; Huberlant, Vincent; Marx, Gernot; Mercier, Emanuelle; Oueslati, Haikel; Hartmann, Oliver; Sonneville, Romain; Laterre, Pierre François; Mebazaa, Alexandre; Legrand, Matthieu.

In: Kidney International Reports, Vol. 3, No. 6, 01.11.2018, p. 1424-1433.

Research output: Contribution to journalArticle

Hollinger, A, Wittebole, X, François, B, Pickkers, P, Antonelli, M, Gayat, E, Chousterman, BG, Lascarrou, JB, Dugernier, T, Di Somma, S, Struck, J, Bergmann, A, Beishuizen, A, Constatin, JM, Damoisel, C, Deye, N, Gaudry, S, Huberlant, V, Marx, G, Mercier, E, Oueslati, H, Hartmann, O, Sonneville, R, Laterre, PF, Mebazaa, A & Legrand, M 2018, 'Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study', Kidney International Reports, vol. 3, no. 6, pp. 1424-1433. https://doi.org/10.1016/j.ekir.2018.08.006
Hollinger, Alexa ; Wittebole, Xavier ; François, Bruno ; Pickkers, Peter ; Antonelli, Massimo ; Gayat, Etienne ; Chousterman, Benjamin Glen ; Lascarrou, Jean Baptiste ; Dugernier, Thierry ; Di Somma, Salvatore ; Struck, Joachim ; Bergmann, Andreas ; Beishuizen, Albertus ; Constatin, Jean Michel ; Damoisel, Charles ; Deye, Nicolas ; Gaudry, Stéphane ; Huberlant, Vincent ; Marx, Gernot ; Mercier, Emanuelle ; Oueslati, Haikel ; Hartmann, Oliver ; Sonneville, Romain ; Laterre, Pierre François ; Mebazaa, Alexandre ; Legrand, Matthieu. / Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury : The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. In: Kidney International Reports. 2018 ; Vol. 3, No. 6. pp. 1424-1433.
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abstract = "Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22{\%} (95{\%} confidence interval [CI] 19{\%}−25{\%}). Of the patients, 293 (50.3{\%}) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95{\%} CI = 1.8–6.0], 3.9 [95{\%} CI = 2.1–7.2], and 3.4 [95{\%} CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients.",
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author = "Alexa Hollinger and Xavier Wittebole and Bruno Fran{\cc}ois and Peter Pickkers and Massimo Antonelli and Etienne Gayat and Chousterman, {Benjamin Glen} and Lascarrou, {Jean Baptiste} and Thierry Dugernier and {Di Somma}, Salvatore and Joachim Struck and Andreas Bergmann and Albertus Beishuizen and Constatin, {Jean Michel} and Charles Damoisel and Nicolas Deye and St{\'e}phane Gaudry and Vincent Huberlant and Gernot Marx and Emanuelle Mercier and Haikel Oueslati and Oliver Hartmann and Romain Sonneville and Laterre, {Pierre Fran{\cc}ois} and Alexandre Mebazaa and Matthieu Legrand",
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TY - JOUR

T1 - Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury

T2 - The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

AU - Hollinger, Alexa

AU - Wittebole, Xavier

AU - François, Bruno

AU - Pickkers, Peter

AU - Antonelli, Massimo

AU - Gayat, Etienne

AU - Chousterman, Benjamin Glen

AU - Lascarrou, Jean Baptiste

AU - Dugernier, Thierry

AU - Di Somma, Salvatore

AU - Struck, Joachim

AU - Bergmann, Andreas

AU - Beishuizen, Albertus

AU - Constatin, Jean Michel

AU - Damoisel, Charles

AU - Deye, Nicolas

AU - Gaudry, Stéphane

AU - Huberlant, Vincent

AU - Marx, Gernot

AU - Mercier, Emanuelle

AU - Oueslati, Haikel

AU - Hartmann, Oliver

AU - Sonneville, Romain

AU - Laterre, Pierre François

AU - Mebazaa, Alexandre

AU - Legrand, Matthieu

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients.

AB - Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients.

KW - acute kidney injury

KW - biomarker

KW - diagnosis

KW - sepsis

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