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

Dana E. McClintock, Barry Starcher, Mark D. Eisner, B. Taylor Thompson, Doug L. Hayden, Gwynne D. Church, Michael A. Matthay, Herbert P. Wiedemann, Alejandro C. Arroliga, Charles J. Fisher, John J. Komara, Patricia Periz-Trepichio, Polly E. Parsons, Carolyn Welsh, William J. Fulkerson, Neil MacIntyre, Lee Mallatratt, Mark Sebastian, John Davies, Elizabeth Van DyneJoseph Govert, Jonathan Sevransky, Stacey Murray, Roy G Brower, David Thompson, Henry Eric Fessler, Alan H. Morris, Terry Clemmer, Robin Davis, James Orme, Lindell Weaver, Colin Grissom, Frank Thomas, Martin Gleich, Charles Lawton, Janice D'Hulst, Joel R. Peerless, Carolyn Smith, Richard Kallet, John M. Luce, Jonathan Gottlieb, Pauline Park, Aimee Girod, Lisa Yannarell, Michael A. Matthay, Mark D. Eisner, Brian Daniel, Edward Abraham, Fran Piedalue, Rebecca Jagusch, Paul Miller, Robert McIntyre, Kelley E. Greene, Henry J. Silverman, Carl Shanholtz, Wanda Corral, Galen B. Toews, Deborah Arnoldi, Robert H. Bartlett, Ron Dechert, Charles Watts, Paul N. Lanken, Harry Anderson, Barbara Finkel, C. William Hanson, Richard Barton, Mary Mone, Leonard D. Hudson, Greg Carter, Claudette Lee Cooper, Annemieke Hiemstra, Ronald V. Maier, Kenneth P. Steinberg, Tracy Hill, Phil Thaut, Arthur P. Wheeler, Gordon Bernard, Brian Christman, Susan Bozeman, Linda Collins, Teresa Swope, Lorraine B. Ware, David A. Schoenfeld, B. Taylor Thompson, Marek Ancukiewicz, Douglas Hayden, Francine Molay, Nancy Ringwood, Gail Wenzlow, Ali S. Kazeroonin, Dorothy B. Gail, Andrea Harabin, Pamela Lew, Myron Waclawiw, Gordon R. Bernard, Roger G. Spragg, James Boyett, Jason Kelley, Kenneth Leeper, Marion Gray Secundy, Arthur Slutsky, Joe G N Garcia, Scott S. Emerson, Susan K. Pingleton, Michael D. Shasby, William J. Sibbald

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number4
DOIs
StatePublished - 2006

Fingerprint

Desmosine
Acute Lung Injury
Urine
Mortality
Tidal Volume
Creatinine
Body Weight
Elastin
Adult Respiratory Distress Syndrome
Mechanical Ventilators
Radioimmunoassay
Extracellular Matrix

Keywords

  • Acute respiratory distress syndrome
  • Extracellular matrix
  • Stretch injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Higher urine desmosine levels are associated with mortality in patients with acute lung injury. / McClintock, Dana E.; Starcher, Barry; Eisner, Mark D.; Thompson, B. Taylor; Hayden, Doug L.; Church, Gwynne D.; Matthay, Michael A.; Wiedemann, Herbert P.; Arroliga, Alejandro C.; Fisher, Charles J.; Komara, John J.; Periz-Trepichio, Patricia; Parsons, Polly E.; Welsh, Carolyn; Fulkerson, William J.; MacIntyre, Neil; Mallatratt, Lee; Sebastian, Mark; Davies, John; Van Dyne, Elizabeth; Govert, Joseph; Sevransky, Jonathan; Murray, Stacey; Brower, Roy G; Thompson, David; Fessler, Henry Eric; Morris, Alan H.; Clemmer, Terry; Davis, Robin; Orme, James; Weaver, Lindell; Grissom, Colin; Thomas, Frank; Gleich, Martin; Lawton, Charles; D'Hulst, Janice; Peerless, Joel R.; Smith, Carolyn; Kallet, Richard; Luce, John M.; Gottlieb, Jonathan; Park, Pauline; Girod, Aimee; Yannarell, Lisa; Matthay, Michael A.; Eisner, Mark D.; Daniel, Brian; Abraham, Edward; Piedalue, Fran; Jagusch, Rebecca; Miller, Paul; McIntyre, Robert; Greene, Kelley E.; Silverman, Henry J.; Shanholtz, Carl; Corral, Wanda; Toews, Galen B.; Arnoldi, Deborah; Bartlett, Robert H.; Dechert, Ron; Watts, Charles; Lanken, Paul N.; Anderson, Harry; Finkel, Barbara; Hanson, C. William; Barton, Richard; Mone, Mary; Hudson, Leonard D.; Carter, Greg; Cooper, Claudette Lee; Hiemstra, Annemieke; Maier, Ronald V.; Steinberg, Kenneth P.; Hill, Tracy; Thaut, Phil; Wheeler, Arthur P.; Bernard, Gordon; Christman, Brian; Bozeman, Susan; Collins, Linda; Swope, Teresa; Ware, Lorraine B.; Schoenfeld, David A.; Thompson, B. Taylor; Ancukiewicz, Marek; Hayden, Douglas; Molay, Francine; Ringwood, Nancy; Wenzlow, Gail; Kazeroonin, Ali S.; Gail, Dorothy B.; Harabin, Andrea; Lew, Pamela; Waclawiw, Myron; Bernard, Gordon R.; Spragg, Roger G.; Boyett, James; Kelley, Jason; Leeper, Kenneth; Secundy, Marion Gray; Slutsky, Arthur; Garcia, Joe G N; Emerson, Scott S.; Pingleton, Susan K.; Shasby, Michael D.; Sibbald, William J.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 4, 2006.

Research output: Contribution to journalArticle

McClintock, DE, Starcher, B, Eisner, MD, Thompson, BT, Hayden, DL, Church, GD, Matthay, MA, Wiedemann, HP, Arroliga, AC, Fisher, CJ, Komara, JJ, Periz-Trepichio, P, Parsons, PE, Welsh, C, Fulkerson, WJ, MacIntyre, N, Mallatratt, L, Sebastian, M, Davies, J, Van Dyne, E, Govert, J, Sevransky, J, Murray, S, Brower, RG, Thompson, D, Fessler, HE, Morris, AH, Clemmer, T, Davis, R, Orme, J, Weaver, L, Grissom, C, Thomas, F, Gleich, M, Lawton, C, D'Hulst, J, Peerless, JR, Smith, C, Kallet, R, Luce, JM, Gottlieb, J, Park, P, Girod, A, Yannarell, L, Matthay, MA, Eisner, MD, Daniel, B, Abraham, E, Piedalue, F, Jagusch, R, Miller, P, McIntyre, R, Greene, KE, Silverman, HJ, Shanholtz, C, Corral, W, Toews, GB, Arnoldi, D, Bartlett, RH, Dechert, R, Watts, C, Lanken, PN, Anderson, H, Finkel, B, Hanson, CW, Barton, R, Mone, M, Hudson, LD, Carter, G, Cooper, CL, Hiemstra, A, Maier, RV, Steinberg, KP, Hill, T, Thaut, P, Wheeler, AP, Bernard, G, Christman, B, Bozeman, S, Collins, L, Swope, T, Ware, LB, Schoenfeld, DA, Thompson, BT, Ancukiewicz, M, Hayden, D, Molay, F, Ringwood, N, Wenzlow, G, Kazeroonin, AS, Gail, DB, Harabin, A, Lew, P, Waclawiw, M, Bernard, GR, Spragg, RG, Boyett, J, Kelley, J, Leeper, K, Secundy, MG, Slutsky, A, Garcia, JGN, Emerson, SS, Pingleton, SK, Shasby, MD & Sibbald, WJ 2006, 'Higher urine desmosine levels are associated with mortality in patients with acute lung injury', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 291, no. 4. https://doi.org/10.1152/ajplung.00457.2005
McClintock, Dana E. ; Starcher, Barry ; Eisner, Mark D. ; Thompson, B. Taylor ; Hayden, Doug L. ; Church, Gwynne D. ; Matthay, Michael A. ; Wiedemann, Herbert P. ; Arroliga, Alejandro C. ; Fisher, Charles J. ; Komara, John J. ; Periz-Trepichio, Patricia ; Parsons, Polly E. ; Welsh, Carolyn ; Fulkerson, William J. ; MacIntyre, Neil ; Mallatratt, Lee ; Sebastian, Mark ; Davies, John ; Van Dyne, Elizabeth ; Govert, Joseph ; Sevransky, Jonathan ; Murray, Stacey ; Brower, Roy G ; Thompson, David ; Fessler, Henry Eric ; Morris, Alan H. ; Clemmer, Terry ; Davis, Robin ; Orme, James ; Weaver, Lindell ; Grissom, Colin ; Thomas, Frank ; Gleich, Martin ; Lawton, Charles ; D'Hulst, Janice ; Peerless, Joel R. ; Smith, Carolyn ; Kallet, Richard ; Luce, John M. ; Gottlieb, Jonathan ; Park, Pauline ; Girod, Aimee ; Yannarell, Lisa ; Matthay, Michael A. ; Eisner, Mark D. ; Daniel, Brian ; Abraham, Edward ; Piedalue, Fran ; Jagusch, Rebecca ; Miller, Paul ; McIntyre, Robert ; Greene, Kelley E. ; Silverman, Henry J. ; Shanholtz, Carl ; Corral, Wanda ; Toews, Galen B. ; Arnoldi, Deborah ; Bartlett, Robert H. ; Dechert, Ron ; Watts, Charles ; Lanken, Paul N. ; Anderson, Harry ; Finkel, Barbara ; Hanson, C. William ; Barton, Richard ; Mone, Mary ; Hudson, Leonard D. ; Carter, Greg ; Cooper, Claudette Lee ; Hiemstra, Annemieke ; Maier, Ronald V. ; Steinberg, Kenneth P. ; Hill, Tracy ; Thaut, Phil ; Wheeler, Arthur P. ; Bernard, Gordon ; Christman, Brian ; Bozeman, Susan ; Collins, Linda ; Swope, Teresa ; Ware, Lorraine B. ; Schoenfeld, David A. ; Thompson, B. Taylor ; Ancukiewicz, Marek ; Hayden, Douglas ; Molay, Francine ; Ringwood, Nancy ; Wenzlow, Gail ; Kazeroonin, Ali S. ; Gail, Dorothy B. ; Harabin, Andrea ; Lew, Pamela ; Waclawiw, Myron ; Bernard, Gordon R. ; Spragg, Roger G. ; Boyett, James ; Kelley, Jason ; Leeper, Kenneth ; Secundy, Marion Gray ; Slutsky, Arthur ; Garcia, Joe G N ; Emerson, Scott S. ; Pingleton, Susan K. ; Shasby, Michael D. ; Sibbald, William J. / Higher urine desmosine levels are associated with mortality in patients with acute lung injury. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2006 ; Vol. 291, No. 4.
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abstract = "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.",
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T1 - Higher urine desmosine levels are associated with mortality in patients with acute lung injury

AU - McClintock, Dana E.

AU - Starcher, Barry

AU - Eisner, Mark D.

AU - Thompson, B. Taylor

AU - Hayden, Doug L.

AU - Church, Gwynne D.

AU - Matthay, Michael A.

AU - Wiedemann, Herbert P.

AU - Arroliga, Alejandro C.

AU - Fisher, Charles J.

AU - Komara, John J.

AU - Periz-Trepichio, Patricia

AU - Parsons, Polly E.

AU - Welsh, Carolyn

AU - Fulkerson, William J.

AU - MacIntyre, Neil

AU - Mallatratt, Lee

AU - Sebastian, Mark

AU - Davies, John

AU - Van Dyne, Elizabeth

AU - Govert, Joseph

AU - Sevransky, Jonathan

AU - Murray, Stacey

AU - Brower, Roy G

AU - Thompson, David

AU - Fessler, Henry Eric

AU - Morris, Alan H.

AU - Clemmer, Terry

AU - Davis, Robin

AU - Orme, James

AU - Weaver, Lindell

AU - Grissom, Colin

AU - Thomas, Frank

AU - Gleich, Martin

AU - Lawton, Charles

AU - D'Hulst, Janice

AU - Peerless, Joel R.

AU - Smith, Carolyn

AU - Kallet, Richard

AU - Luce, John M.

AU - Gottlieb, Jonathan

AU - Park, Pauline

AU - Girod, Aimee

AU - Yannarell, Lisa

AU - Matthay, Michael A.

AU - Eisner, Mark D.

AU - Daniel, Brian

AU - Abraham, Edward

AU - Piedalue, Fran

AU - Jagusch, Rebecca

AU - Miller, Paul

AU - McIntyre, Robert

AU - Greene, Kelley E.

AU - Silverman, Henry J.

AU - Shanholtz, Carl

AU - Corral, Wanda

AU - Toews, Galen B.

AU - Arnoldi, Deborah

AU - Bartlett, Robert H.

AU - Dechert, Ron

AU - Watts, Charles

AU - Lanken, Paul N.

AU - Anderson, Harry

AU - Finkel, Barbara

AU - Hanson, C. William

AU - Barton, Richard

AU - Mone, Mary

AU - Hudson, Leonard D.

AU - Carter, Greg

AU - Cooper, Claudette Lee

AU - Hiemstra, Annemieke

AU - Maier, Ronald V.

AU - Steinberg, Kenneth P.

AU - Hill, Tracy

AU - Thaut, Phil

AU - Wheeler, Arthur P.

AU - Bernard, Gordon

AU - Christman, Brian

AU - Bozeman, Susan

AU - Collins, Linda

AU - Swope, Teresa

AU - Ware, Lorraine B.

AU - Schoenfeld, David A.

AU - Thompson, B. Taylor

AU - Ancukiewicz, Marek

AU - Hayden, Douglas

AU - Molay, Francine

AU - Ringwood, Nancy

AU - Wenzlow, Gail

AU - Kazeroonin, Ali S.

AU - Gail, Dorothy B.

AU - Harabin, Andrea

AU - Lew, Pamela

AU - Waclawiw, Myron

AU - Bernard, Gordon R.

AU - Spragg, Roger G.

AU - Boyett, James

AU - Kelley, Jason

AU - Leeper, Kenneth

AU - Secundy, Marion Gray

AU - Slutsky, Arthur

AU - Garcia, Joe G N

AU - Emerson, Scott S.

AU - Pingleton, Susan K.

AU - Shasby, Michael D.

AU - Sibbald, William J.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - Acute respiratory distress syndrome

KW - Extracellular matrix

KW - Stretch injury

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