Higher urine desmosine levels are associated with mortality in patients with acute lung injury

1 Cardiovascular Research Institute and 3 Division of Occupational and Environmental Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, California; 2 University of Texas Health Center at Tyler, Department of Biochemistry, Tyler, Texas; 4 Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, and 5 Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts Submitted 31 October 2005 ; accepted in final form 4 May 2006 Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0 , 1 , and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline ( day 0 ) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02–1.82, P = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3 , but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group ( P = 0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury. acute respiratory distress syndrome; extracellular matrix; stretch injury Address for reprint requests and other correspondence: D. McClintock, Cardiovascular Research Institute, Univ. of California, San Francisco, 505 Parnassus Ave., San Francisco, CA 94143-0130 (e-mail: dana.mcclintock{at}ucsf.edu )