Mortality and host response aberrations associated with transient and persistent acute kidney injury in critically ill patients with sepsis: a prospective cohort study

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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 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.

Electronic supplementary material

The online version of this article (10.1007/s00134-020-06119-x) contains supplementary material, which is available to authorized users.

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Most cited references 40

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Sepsis and septic shock.

Richard Hotchkiss, Lyle Moldawer, Steven M Opal … (2016)

For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.

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Acute kidney injury in sepsis.

Rinaldo Bellomo, John A. Kellum, Claudio Ronco … (2017)

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.

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Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes.

Sean Bagshaw, Shigehiko Uchino, Rinaldo Bellomo … (2007)

Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P = 0.83). Oliguria was more common in septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P < 0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P = 0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P < 0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] mumol/L; P = 0.01) and RRT dependence (9 versus 14%; P = 0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT.

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Author and article information

Contributors

Fabrice Uhel:

ORCID: http://orcid.org/0000-0003-4946-8184

dr.f.uhel@gmail.com

Journal

Journal ID (nlm-ta): Intensive Care Med

Journal ID (iso-abbrev): Intensive Care Med

Title: Intensive Care Medicine

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0342-4642

ISSN (Electronic): 1432-1238

Publication date (Electronic): 8 June 2020

Publication date PMC-release: 8 June 2020

Publication date (Print): 2020

Volume: 46

Issue: 8

Pages: 1576-1589

Affiliations

[1 ]GRID grid.7177.6, ISNI 0000000084992262, Center for Experimental and Molecular Medicine, , Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, ; Room G2-130; Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

[2 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, , Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, ; Amsterdam, The Netherlands

[3 ]GRID grid.7692.a, ISNI 0000000090126352, Department of Medical Microbiology, , University Medical Center Utrecht, ; Utrecht, The Netherlands

[4 ]GRID grid.7692.a, ISNI 0000000090126352, Julius Center for Health Sciences and Primary Care, , University Medical Center Utrecht, ; Utrecht, The Netherlands

[5 ]GRID grid.7692.a, ISNI 0000000090126352, Department of Intensive Care Medicine, , University Medical Center Utrecht, ; Utrecht, The Netherlands

[6 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Intensive Care Medicine, and Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), , Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, ; Amsterdam, The Netherlands

[7 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Mahidol-Oxford Tropical Medicine Research Unit (MORU), , Mahidol University, ; Bangkok, Thailand

[8 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of medicine, , University of Oxford, ; Oxford, UK

[9 ]GRID grid.7177.6, ISNI 0000000084992262, Division of Infectious Diseases, , Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, ; Amsterdam, The Netherlands

Author information

Fabrice Uhel http://orcid.org/0000-0003-4946-8184

Article

Publisher ID: 6119

DOI: 10.1007/s00134-020-06119-x

PMC ID: 7381452

PubMed ID: 32514599

SO-VID: 6a813360-d82b-4555-b815-c8edb4ce4a30

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 14 February 2020

Date accepted : 14 May 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100006020, Center for Translational Molecular Medicine;

Award ID: 04I-201

Funded by: FundRef http://dx.doi.org/10.13039/501100002997, Nierstichting;

Award ID: 19OK009

Award Recipient : Hessel Peters-Sengers

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: sepsis,acute kidney injury,host response,mortality,intensive care unit

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: sepsis, acute kidney injury, host response, mortality, intensive care unit

Mortality and host response aberrations associated with transient and persistent acute kidney injury in critically ill patients with sepsis: a prospective cohort study

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Most cited references 40

Sepsis and septic shock.

Acute kidney injury in sepsis.

Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes.

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