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Impact of angiotensin-converting enzyme inhibitors or receptor blockers on post-ICU discharge outcome in patients with acute kidney injury

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Abstract

Purpose

Acute kidney injury (AKI) is associated with the activation of the renin–angiotensin system. Whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) improve outcome in patients recovering from AKI remains unexplored. The purpose was to investigate the association between prescription of ACEi/ARB at intensive care unit (ICU) discharge and 1-year outcome in patients recovering from AKI.

Methods

Association between ACEi/ARB and 1-year mortality rate was explored in 1551 patients discharged from 21 European ICUs in an observational cohort. One-year all-cause mortality after ICU discharge was the primary endpoint. AKI was defined using the kidney disease improvement global outcome definition. Propensity score matching was used to consider the probability to receive ACEi/ARB at ICU discharge and included chronic heart failure, ACEi/ARB on ICU admission, Charlson Comorbidity Index, age, diabetes mellitus, chronic kidney disease, estimated glomerular filtration rate and arterial blood pressure at ICU discharge vasopressors and renal replacement therapy.

Results

Overall, 1-year mortality was 28 and 15% in patients with AKI (n = 611, 39%) and without AKI (n = 940), respectively. In patients with AKI, unadjusted, adjusted and propensity-score matched 1-year mortality rates were lower in patients treated with ACEi/ARB at ICU discharge [HR of 0.55 (0.35–0.89), HR of 0.45 (0.27–0.75), and HR of 0.48 (0.27–0.85, p < 0.001), respectively]. These results were consistent across sensitivity analysis. No association was observed in patients without AKI.

Conclusions

In patients discharged alive from the ICU after experiencing AKI, ACEi/ARB prescription at discharge is associated with a decrease in 1-year mortality.

Trial registration

ClinicalTrials.gov NCT01367093. Registered on 6 June 2011.

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Acknowledgements

The authors are particularly grateful to CRAs and healthcare providers of all the investigating centers. We also thank the Centre de Recherche Clinique (CRC) of Lariboisière University Hospital for his support.

Funding

FROG-ICU was funded by the Programme Hospitalier de la Recherche Clinique (AON 10-216) and by a research grant from the Société Française d’Anesthésie—Réanimation.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, Critical Care Medicine and Burn Unit, Saint Louis and Lariboisière University Hospitals, AP-HP, 2 rue A. Paré, 75010, Paris, France

    Etienne Gayat, Alexa Hollinger, Benjamin G. Chousterman, Marie-Céline Fournier, Alexandre Mebazaa & Matthieu Legrand

  2. Institut National de la Santé et de la Recherche Médicale (INSERM), Lariboisière Hospital and INI-CRCT Network, INSERM UMR-S942, Paris, France

    Etienne Gayat, Alexa Hollinger, Nicolas Deye, Marie-Céline Fournier, Alexandre Mebazaa & Matthieu Legrand

  3. University Paris Diderot, 75475, Paris, France

    Etienne Gayat, Alexandre Mebazaa & Matthieu Legrand

  4. Department of Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland

    Alexa Hollinger

  5. Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Alain Cariou

  6. Medical and Toxicological Intensive Care Unit, Lariboisière Hospital, Université Paris Sorbonne Cité, Paris Diderot, Assistance Publique des Hôpitaux de Paris, Paris, France

    Nicolas Deye

  7. Intensive Care Unit, University Hospital Ambroise Paré, Assistance Publique-Hopitaux de Paris, 26930, Boulogne-Billancourt, France

    Antoine Vieillard-Baron

  8. INSERM U-1018, CESP, Team 5, University of Versailles Saint-Quentin en Yvelines, Villejuif, France

    Antoine Vieillard-Baron

  9. Faculty of Medicine Paris Ile-de-France Ouest, University of Versailles Saint-Quentin en Yvelines, Saint-Quentin en Yvelines, France

    Antoine Vieillard-Baron

  10. Intensive Care Unit, Anaesthesia and Critical Care Department, Saint Eloi Teaching Hospital, Centre Hospitalier Universitaire Montpellier, Montpellier University, Montpellier, France

    Samir Jaber

  11. Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, UPMC Paris 6, Paris, France

    Qin Lu

  12. Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Pierre François Laterre

  13. Medical Intensive Care Unit, Bicêtre Hospital, Paris-Sud University Hospitals, Inserm UMR_S999, Paris-Sud University, Le Kremlin-Bicêtre, France

    Xavier Monnet

  14. Medical ICU, St-Louis Hospital, Université Paris Sorbonne Cité, Paris Diderot, Assistance Publique des Hôpitaux de Paris, Paris, France

    Michael Darmon

  15. Service d’anesthésie et de réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France

    Marc Leone

  16. Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France

    Bertrand Guidet

  17. Medical ICU, Bichat Hospital, Université Paris Sorbonne Cité, Paris Diderot, Assistance Publique des Hôpitaux de Paris, Paris, France

    Romain Sonneville

  18. Department of Anesthesiology, Critical Care, Emergency and Pain Medicine, Nimes University Hospital, 30029, Nîmes, France

    Jean-Yves Lefrant

  19. ECSTRA Team, INSERM, Service de biostatistique et information Médicale, Hôpitaux Universitaires St-Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, Paris, France

    Matthieu Resche-Rigon

Authors
  1. Etienne Gayat
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  2. Alexa Hollinger
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  3. Alain Cariou
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  4. Nicolas Deye
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  8. Qin Lu
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  9. Pierre François Laterre
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  10. Xavier Monnet
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  12. Marc Leone
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  17. Matthieu Resche-Rigon
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  18. Alexandre Mebazaa
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  19. Matthieu Legrand
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Consortia

On behalf of FROG-ICU investigators

Contributions

Study concept and design: Gayat, Legrand, Mebazaa; Acquisition of data: Gayat, Mebazaa, Vieillard-Baron, Cariou, Deye, Jaber, Chousterman, Lu, Laterre, Monnet, Leone, Guidet, Lefrant, Fournier, Legrand; Analysis and interpretation of data: Gayat, Legrand, Mebazaa; Drafting of the manuscript: Legrand, Gayat, Hollinger, Mebazaa; Critical revision of the manuscript for important intellectual content: all declared authors; Statistical analysis: Gayat; Obtained funding: Gayat, Mebazaa; Administrative, technical, or material support: Gayat, Mebazaa, Fournier; Study supervision: Gayat, Legrand, Mebazaa; All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Matthieu Legrand.

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Conflicts of interest

EG received research grants from Sphingotec, and consultancy fees from Magnisense and Roche Diagnostics. AM received speaker’s honoraria from Abbott, Novartis, Orion, Roche and Servier, and fees as a member of the advisory board and/or Steering Committee from Cardiorentis, Adrenomed, MyCartis, Neurotronik and Sphyngotec. ML received research grants from Sphingotec, consultancy fees from Astellas and Lecture fees from Gilead and Fresenius. The remaining authors declare that they have no competing interests.

Electronic supplementary material

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134_2018_5160_MOESM1_ESM.tiff

eFigure 1. Imbalance before (black square) and after (red bullet) propensity score matching for variables included in the propensity model with patients who developed AKI during ICU stay (TIFF 61 kb)

134_2018_5160_MOESM2_ESM.tiff

eFigure 2. Survival curves according to prescription of ACEi at ICU discharge in patients without AKI (Panel A) and Imbalance before (black square) and after (red bullet) propensity score matching for variables included in the propensity model with patients who didn’t developed AKI during ICU stay(Panel B) (TIFF 220 kb)

Supplementary material 3 (DOCX 110 kb)

Supplementary material 4 (DOCX 21 kb)

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Gayat, E., Hollinger, A., Cariou, A. et al. Impact of angiotensin-converting enzyme inhibitors or receptor blockers on post-ICU discharge outcome in patients with acute kidney injury. Intensive Care Med 44, 598–605 (2018). https://doi.org/10.1007/s00134-018-5160-6

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  • DOI: https://doi.org/10.1007/s00134-018-5160-6

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