Urinary protein profiling in hyperactive delirium and non-delirium cardiac surgery ICU patients

Mark van den Boogaard, Rachel Pl van Swelm, Frans Gm Russel, Suzanne Heemskerk, Johannes G van der Hoeven, Rosalinde Masereeuw, Peter Pickkers, Mark van den Boogaard, Rachel Pl van Swelm, Frans Gm Russel, Suzanne Heemskerk, Johannes G van der Hoeven, Rosalinde Masereeuw, Peter Pickkers

Abstract

Background: Suitable biomarkers associated with the development of delirium are still not known. Urinary proteomics has successfully been applied to identify novel biomarkers associated with various disease states, but its value has not been investigated in delirium patients.

Results: In a prospective explorative study hyperactive delirium patients after cardiac surgery were included for urinary proteomic analyses. Delirium patients were matched with non-delirium patients after cardiac surgery on age, gender, severity of illness score, LOS-ICU, Euro-score, C-reactive protein, renal function and aorta clamping time. Urine was collected within 24 hours after the onset of delirium. Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) was applied to detect differences in the urinary proteome associated with delirium in these ICU patients. We included 10 hyperactive delirium and 10 meticulously matched non-delirium post-cardiac surgery patients. No relevant differences in the urinary excretion of proteins could be observed.

Conclusions: We conclude that MALDI-TOF MS of urine does not reveal a clear hyperactive delirium proteome fingerprint in ICU patients.

Trial registration: Clinical Trial Register number: NCT00604773.

Figures

Figure 1
Figure 1
Protein spectra and hierarchical cluster after profiling with CM10 beads. A. Protein spectra of masterpool urine (upper panel), a non-delirium patient (middle panel) and a delirium patient (lower panel). The x-axis depicts m/z values in Dalton; the y-axis shows the relative peak intensity. B. Unsupervised hierarchical clustering determines whether patient groups can be differentiated solely based on their urine protein profile. On the right hand side the samples are represented. The lengths of the horizontal lines represent the resemblance of the spectra; the shortest lines represent the most alikeness between samples. In this hierarchic cluster our masterpool can be clearly distinguished from the ICU patients, but there is no distinction between delirium and non-delirium patients.

References

    1. Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T. et al.The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001;27:1892–900. doi: 10.1007/s00134-001-1132-2.
    1. Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK. et al.Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc. 2006;54:479–84. doi: 10.1111/j.1532-5415.2005.00621.x.
    1. Maclullich AM, Ferguson KJ, Miller T, de Rooij SE, Cunningham C. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008;65:229–38. doi: 10.1016/j.jpsychores.2008.05.019.
    1. Marcantonio ER, Rudolph JL, Culley D, Crosby G, Alsop D, Inouye SK. Serum biomarkers for delirium. J Gerontol A Biol Sci Med Sci. 2006;61:1281–6.
    1. Zhu P, Bowden P, Zhang D, Marshall JG. Mass spectrometry of peptides and proteins from human blood. Mass Spectrom. 2011. in press .
    1. Sultana R, Reed T, Perluigi M, Coccia R, Pierce WM, Butterfield DA. Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: a regional study. J Cell Mol Med. 2007;11:839–51. doi: 10.1111/j.1582-4934.2007.00065.x.
    1. Biroccio A, Del BP, Panella M, Bernardini S, Di IC, Gambi D. et al.Differential post-translational modifications of transthyretin in Alzheimer's disease: a study of the cerebral spinal fluid. Proteomics. 2006;6:2305–13. doi: 10.1002/pmic.200500285.
    1. van Munster BC, van Breemen MJ, Moerland PD, Speijer D, de Rooij SE, Pfrommer CJ. et al.Proteomic profiling of plasma and serum in elderly patients with delirium. J Neuropsychiatry Clin Neurosci. 2009;21:284–91.
    1. Xi L, Junjian Z, Yumin L, Yunwen L, Hongbin W. Serum biomarkers of vascular cognitive impairment evaluated by bead-based proteomic technology. Neurosci Lett. 2009;463:6–11. doi: 10.1016/j.neulet.2009.07.056.
    1. Geng T, Seitz PK, Thomas ML, Xu B, Soman KV, Kurosky A. et al.Use of surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) to study protein expression in a rat model of cocaine withdrawal. J Neurosci Methods. 2006;158:1–12. doi: 10.1016/j.jneumeth.2006.04.025.
    1. Papale M, Pedicillo MC, Thatcher BJ, Di PS, Lo ML, Bufo P. et al.Urine profiling by SELDI-TOF/MS: monitoring of the critical steps in sample collection, handling and analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;856:205–13. doi: 10.1016/j.jchromb.2007.06.001.
    1. Decramer S, Gonzalez de PA, Breuil B, Mischak H, Monsarrat B, Bascands JL. et al.Urine in clinical proteomics. Mol Cell Proteomics. 2008;7:1850–62. doi: 10.1074/mcp.R800001-MCP200.
    1. Vanhoutte KJ, Laarakkers C, Marchiori E, Pickkers P, Wetzels JF, Willems JL. et al.Biomarker discovery with SELDI-TOF MS in human urine associated with early renal injury: evaluation with computational analytical tools. Nephrol Dial Transplant. 2007;22:2932–43. doi: 10.1093/ndt/gfm170.
    1. van Munster BC, Bisschop PH, Zwinderman AH, Korevaar JC, Endert E, Wiersinga WJ. et al.Cortisol, interleukins and S100B in delirium in the elderly. Brain Cogn. 2010;74(1):18–23. doi: 10.1016/j.bandc.2010.05.010.
    1. van Munster BC, korevaar JC, Korse CM, Bonfrer JM, Zwinderman AH, de Rooij SE. Serum S100B in elderly patients with and without delirium. Int J Geriatr Psychiatry. 2010;25(3):234–9. doi: 10.1002/gps.2326.
    1. Fliser D, Novak J, Thongboonkerd V, Argiles A, Jankowski V, Girolami MA. et al.Advances in urinary proteome analysis and biomarker discovery. J Am Soc Nephrol. 2007;18:1057–71. doi: 10.1681/ASN.2006090956.
    1. Wahlberg E, Dimuzio PJ, Stoney RJ. Aortic clamping during elective operations for infrarenal disease: The influence of clamping time on renal function. J Vasc Surg. 2002;36:13–8. doi: 10.1067/mva.2002.123679.
    1. Vreeswijk R, Toornvliet A, Honing M, Bakker K, de Man T, Daas G. et al.Validation of the Dutch version of the Confusion Assessment Method (CAM-ICU) for delirium screening in the Intensive Care Unit. Netherlands Journal of Critical Care. 2009;13:73–8.
    1. van den Boogaard M, Pickkers P, van der Hoeven H, Roodbol G, van Achterberg T, Schoonhoven L. Implementation of a delirium assessment tool in the ICU can influence haloperidol use. Crit Care. 2009;13:R131. doi: 10.1186/cc7991.
    1. Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for intensive care delirium: A systematic review. Intensive Crit Care Nurs. 2008;24:98–107. doi: 10.1016/j.iccn.2007.08.005.
    1. Fiedler GM, Baumann S, Leichtle A, Oltmann A, Kase J, Thiery J. et al.Standardized peptidome profiling of human urine by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Clin Chem. 2007;53:421–8. doi: 10.1373/clinchem.2006.077834.
    1. Swinkels DW, Girelli D, Laarakkers C, Kroot J, Campostrini N, Kemna EH. et al.Advances in quantitative hepcidin measurements by time-of-flight mass spectrometry. PLoS One. 2008;3:e2706. doi: 10.1371/journal.pone.0002706.
    1. Kroot JJ, Hendriks JC, Laarakkers CM, Klaver SM, Kemna EH, Tjalsma H. et al.(Pre)analytical imprecision, between-subject variability, and daily variations in serum and urine hepcidin: implications for clinical studies. Anal Biochem. 2009;389:124–9. doi: 10.1016/j.ab.2009.03.039.
    1. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276:7806–10. doi: 10.1074/jbc.M008922200.

Source: PubMed

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