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Higher Plasma Cystatin C is associated with Mortality after Acute Respiratory Distress Syndrome: Findings from a Fluid and Catheter Treatment Trial (FACTT) Substudy
Carolyn M. Hendrickson
University of California San Francisco
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4662-2385
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Critical Care.
Background: Cystatin C is a well validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous critically-ill populations and may be superior to creatinine in identifying kidney injury in critically-ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with Acute Respiratory Distress Syndrome (ARDS) would be associated with mortality.
Methods: In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by Acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
Results : Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9 – 1.9) mg/L vs. 0.8 (0.6 – 1.2) mg/L, p <0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2-2.6), p =0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0-2.4), p =0.048] and those without AKI [OR 2.4 (1.2-5.0), p =0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.
Conclusions : Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60-days in patients with ARDS with and without AKI identified by creatinine-based definitions . Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.
Keywords
Cystatin C, Acute Respiratory Distress Syndrome (ARDS), Acute Kidney, Injury (AKI)
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CURRENT STATUS: Published
Version 2
Posted 23 Jun, 2020
Published
On 11 Jul, 2020
No community comments so far
Editorial decision: Accept
On 23 Jun, 2020
Editor assigned
On 22 Jun, 2020
Submission checks complete
On 21 Jun, 2020
Editor invited
On 21 Jun, 2020
No comments provided
Editorial decision: Major revision
On 28 Apr, 2020
Review #2 received
Received 21 Apr, 2020
Review #1 received
Received 15 Apr, 2020
Reviewer #2 agreed
On 11 Apr, 2020
Reviewer #1 agreed
On 11 Apr, 2020
Reviewers invited
Invitations sent on 20 Feb, 2020
Editor assigned
On 17 Feb, 2020
Editor invited
On 16 Feb, 2020
Submission checks complete
On 15 Feb, 2020
First submitted
On 13 Feb, 2020
Metrics
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PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
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This preprint is under consideration at Critical Care. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Higher Plasma Cystatin C is associated with Mortality after Acute Respiratory Distress Syndrome: Findings from a Fluid and Catheter Treatment Trial (FACTT) Substudy
Carolyn M. Hendrickson
University of California San Francisco
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4662-2385
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 23 Jun, 2020
Published
On 11 Jul, 2020
No community comments so far
Editorial decision: Accept
On 23 Jun, 2020
Editor assigned
On 22 Jun, 2020
Submission checks complete
On 21 Jun, 2020
Editor invited
On 21 Jun, 2020
No comments provided
Editorial decision: Major revision
On 28 Apr, 2020
Review #2 received
Received 21 Apr, 2020
Review #1 received
Received 15 Apr, 2020
Reviewer #2 agreed
On 11 Apr, 2020
Reviewer #1 agreed
On 11 Apr, 2020
Reviewers invited
Invitations sent on 20 Feb, 2020
Editor assigned
On 17 Feb, 2020
Editor invited
On 16 Feb, 2020
Submission checks complete
On 15 Feb, 2020
First submitted
On 13 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Critical Care.
Background: Cystatin C is a well validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous critically-ill populations and may be superior to creatinine in identifying kidney injury in critically-ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with Acute Respiratory Distress Syndrome (ARDS) would be associated with mortality.
Methods: In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by Acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
Results : Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9 – 1.9) mg/L vs. 0.8 (0.6 – 1.2) mg/L, p <0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2-2.6), p =0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0-2.4), p =0.048] and those without AKI [OR 2.4 (1.2-5.0), p =0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.
Conclusions : Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60-days in patients with ARDS with and without AKI identified by creatinine-based definitions . Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.
Figure 1
Figure 2
Figure 3
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.