Higher plasma cystatin C is associated with mortality after acute respiratory distress syndrome: findings from a Fluid and Catheter Treatment Trial (FACTT) substudy.
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 populations of critically ill patients 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 risk.


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.
['Hendrickson|Carolyn M|CM|0000-0003-4662-2385', 'Kwong|Yuenting D|YD|', 'Belzer|Annika G|AG|', 'Shlipak|Michael G|MG|', 'Matthay|Michael A|MA|', 'Liu|Kathleen D|KD|']
D018806:APACHE D000328:Adult D000368:Aged D015415:Biomarkers D015331:Cohort Studies D000078331:Correlation of Data D055316:Cystatin C D005260:Female D006801:Humans D016015:Logistic Models D008297:Male D008875:Middle Aged D010949:Plasma D011446:Prospective Studies D012128:Respiratory Distress Syndrome D012189:Retrospective Studies
Cystatin C Acute respiratory distress syndrome (ARDS) Acute kidney injury (AKI)