Mortality and host response aberrations associated with transient and persistent acute kidney injury in critically ill patients with sepsis: a prospective cohort study
MARS Consortium
(2020) Intensive Care Medicine, volume 46, issue 8, pp. 1576 - 1589
(Article)
Abstract
PURPOSE: Sepsis is the most frequent cause of acute kidney injury (AKI). The "Acute Disease Quality Initiative Workgroup" recently proposed new definitions for AKI, classifying it as transient or persistent. We investigated the incidence, mortality, and host response aberrations associated with transient and persistent AKI in sepsis patients. METHODS: A
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total of 1545 patients admitted with sepsis to 2 intensive care units in the Netherlands were stratified according to the presence (defined by any urine or creatinine RIFLE criterion within the first 48 h) and evolution of AKI (with persistent defined as remaining > 48 h). We determined 30-day mortality by logistic regression adjusting for confounding variables and analyzed 16 plasma biomarkers reflecting pathways involved in sepsis pathogenesis (n = 866) and blood leukocyte transcriptomes (n = 392). RESULTS: AKI occurred in 37.7% of patients, of which 18.4% was transient and 81.6% persistent. On admission, patients with persistent AKI had higher disease severity scores and more frequently had severe (injury or failure) RIFLE AKI stages than transient AKI patients. Persistent AKI, but not transient AKI, was associated with increased mortality by day 30 and up to 1 year. Persistent AKI was associated with enhanced and sustained inflammatory and procoagulant responses during the first 4 days, and a more severe loss of vascular integrity compared with transient AKI. Baseline blood gene expression showed minimal differences with respect to the presence or evolution of AKI. CONCLUSION: Persistent AKI is independently associated with sepsis mortality, as well as with sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient AKI.
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Keywords: Acute kidney injury, Host response, Intensive care unit, Mortality, Sepsis, Critical Care and Intensive Care Medicine, Journal Article
ISSN: 0342-4642
Publisher: Springer-Verlag
Note: Funding Information: The authors acknowledge all members of the Molecular Diagnosis and Risk Stratification of Sepsis consortium for the participation in data collection and especially acknowledge: Friso M. de Beer, M.D., Lieuwe D. J. Bos, Ph.D., Gerie J. Glas, M.D., Roosmarijn T. M. van Hooijdonk, M.D., Ph.D., Janneke Horn, M.D., Ph.D.,Laura R. A. Schouten, M.D., Marleen Straat, M.D., Luuk Wieske, M.D., Ph.D., Esther Witteveen, M.D., Department of Intensive Care, Academic Medical Center, University of Amsterdam, The Netherlands; Arie J. Hoogendijk, PhD, Mischa A. Huson, M.D., Maryse A. Wiewel, M.D., Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, and Center of Infection and Immunity Amsterdam (CINIMA), Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Peter M.C. Klein Klouwenberg, M.D., Ph.D., David S.Y. Ong, M.D., Ph.D., Department of Medical Microbiology, Department of Intensive Care Medicine, and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Jos F. Frencken, M.D., Maria E. Koster-Brouwer, MSc, Kirsten van de Groep, M.D., Diana M. Verboom, M.D., Department of Intensive Care Medicine and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. Funding Information: This research was performed within the framework of the Center for Translational Molecular Medicine (CTMM) ( www.ctmm.nl ), project Molecular Diagnosis and Risk Stratification of Sepsis (Grant 04I-201). The sponsor CTMM was not involved in the design and conduction of the study; nor was the sponsor involved in collection, management, analysis, and interpretation of the data or preparation, review or approval of the article. H.P.S. was supported by a grant from the Dutch Kidney Foundation (Kolff Grant Nr. 19OK009). Decision to submit the article was not dependent on the sponsor. Acknowledgements Publisher Copyright: © 2020, The Author(s).
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