Skip to main content

Advertisement

SpringerLink
Log in

Microproteinuria Predicts Organ Failure in Patients Presenting with Acute Pancreatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aims

The disease course of acute pancreatitis (AP) ranges from mild and self-limiting to severe inflammation, associated with significant morbidity and mortality. At present, there are no universally accepted and reliable predictors for severity. Microproteinuria has been associated with the presence of systemic inflammatory response syndrome as well as trauma, although its association with AP is not well understood. The aim of this study was to investigate the value of microproteinuria to predict development of organ failure in AP.

Methods

Consecutive AP patients were prospectively enrolled. Urine samples were collected upon admission, 12–24 h after admission, and 3 months post-discharge for calculation of urine α1-microglobulin-, albumin-, IgG-, and IgM/creatinine ratios. Data regarding AP etiology, severity, and development of organ failure were registered.

Results

Overall, 92 AP patients were included (14 % with organ failure; 6 % with severe AP). The α1-microglobulin-, albumin-, and IgG/creatinine ratios correlated with high-sensitivity C-reactive protein 48 h after admission (r = 0.47–0.61, p < 0.001 for all). They were also significantly higher in patients with versus without organ failure (p < 0.05 for all). The α1-microglobulin/creatinine ratio upon admission predicted organ failure [adjusted odds ratio 1.286, 95 % confidence interval (CI) 1.024–1.614] with similar accuracy (AUROC 0.81, 95 % CI 0.69–0.94) as the more complex APACHE II score (AUROC 0.86, 95 % CI 0.70–1.00).

Conclusion

The α1-microglobulin/creatinine ratio upon presentation with AP is related to inflammation and predicts development of organ failure. Further studies are warranted to evaluate its potential usefulness in predicting outcome for AP patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AP:

Acute pancreatitis

SIRS:

Systemic inflammatory response syndrome

CT:

Computed tomography

θ :

Fractional clearance

PTR:

Tubular protein reabsorption

GFB:

Glomerular filtration barrier

hsCRP:

High-sensitivity C-reactive protein

eGFR:

Estimated glomerular filtration rate

ERCP:

Endoscopic retrograde cholangiopancreatography

APACHE II:

The Acute Physiology and Chronic Health Evaluation II

NSAID:

Non-steroidal anti-inflammatory drugs

CCI:

Charlson Comorbidity Index

IQR:

Interquartile range

AUROC:

Area under the receiver operating characteristics curve

ROC:

Receiver operating characteristics

References

  1. Gloor B, Muller CA, Worni M, Martignoni ME, Uhl W, Buchler MW. Late mortality in patients with severe acute pancreatitis. Br J Surg. 2001;88:975–979.

    Article  CAS  PubMed  Google Scholar 

  2. Bertilsson S, Sward P, Kalaitzakis E. Factors that affect disease progression after first attack of acute pancreatitis. Clin Gastroenterol Hepatol. 2015;13:1662–1669.

    Article  PubMed  Google Scholar 

  3. Mounzer R, Langmead CJ, Wu BU, et al. Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology. 2012;142:1476–1482.

    Article  PubMed  Google Scholar 

  4. Gosling P, Sutcliffe AJ, Cooper MA, Jones AF. Burn and trauma associated proteinuria: the role of lipid peroxidation, renin and myoglobin. Ann Clin Biochem. 1988;25:53–59.

    Article  PubMed  Google Scholar 

  5. Haraldsson B, Nystrom J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. 2008;88:451–487.

    Article  CAS  PubMed  Google Scholar 

  6. Weber MH, Verwiebe R. Alpha 1-microglobulin (protein HC): features of a promising indicator of proximal tubular dysfunction. Eur J Clin Chem Clin Biochem. 1992;30:683–691.

    CAS  PubMed  Google Scholar 

  7. Shearman CP, Gosling P, Walker KJ. Is low proteinuria an early predictor of severity of acute pancreatitis? J Clin Pathol. 1989;42:1132–1135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zuidema MJ, van Santvoort HC, Besselink MG, et al. The predictive value of proteinuria in acute pancreatitis. Pancreatology. 2014;14:484–489.

    Article  CAS  PubMed  Google Scholar 

  9. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111.

    Article  PubMed  Google Scholar 

  10. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–829.

    Article  CAS  PubMed  Google Scholar 

  11. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–383.

    Article  CAS  PubMed  Google Scholar 

  12. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309–332.

    Article  PubMed  Google Scholar 

  13. Hartmann S, Aradottir S, Graf M, et al. Phosphatidylethanol as a sensitive and specific biomarker: comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin. Addict Biol. 2007;12:81–84.

    Article  CAS  PubMed  Google Scholar 

  14. Tencer J, Torffvit O, Thysell H, Rippe B, Grubb A. Proteinuria selectivity index based upon alpha 2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases. Technical note. Kidney Int. 1998;54:2098–2105.

    Article  CAS  PubMed  Google Scholar 

  15. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med. 1999;130:461–470.

    Article  CAS  PubMed  Google Scholar 

  16. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845.

    Article  CAS  PubMed  Google Scholar 

  17. Gosling P, Hughes EA, Reynolds TM, Fox JP. Microalbuminuria is an early response following acute myocardial infarction. Eur Heart J. 1991;12:508–513.

    CAS  PubMed  Google Scholar 

  18. Tofik R, Ekelund U, Torffvit O, Sward P, Rippe B, Bakoush O. Increased urinary IgM excretion in patients with chest pain due to coronary artery disease. BMC Cardiovasc Dis. 2013;13:72.

    Article  CAS  Google Scholar 

  19. Hegewald MJ, Isenberg G, Sterling RK, Cooper GS, Chak A, Sivak MV Jr. Evaluation of a rapid urine amylase test using post-ERCP hyperamylasemia as a model. Am J Gastroenterol. 2001;96:2640–2645.

    Article  CAS  PubMed  Google Scholar 

  20. Tencer J, Frick IM, Oquist BW, Alm P, Rippe B. Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways. Kidney Int. 1998;53:709–715.

    Article  CAS  PubMed  Google Scholar 

  21. Blamey SL, Imrie CW, O’Neill J, Gilmour WH, Carter DC. Prognostic factors in acute pancreatitis. Gut. 1984;25:1340–1346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nieminen A, Maksimow M, Mentula P, et al. Circulating cytokines in predicting development of severe acute pancreatitis. Crit Care. 2014;18:R104.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sward P, Rippe B. Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability. Acta Physiol. 2012;204:294–307.

    Article  CAS  Google Scholar 

  24. Oberg CM, Rippe B. A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll. Am J Physiol Renal Physiol. 2014;306:F844–F854.

    Article  CAS  PubMed  Google Scholar 

  25. Deen WM, Bridges CR, Brenner BM, Myers BD. Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. Am J Physiol. 1985;249:F374–F389.

    CAS  PubMed  Google Scholar 

  26. Sverrisson K, Axelsson J, Rippe A, Asgeirsson D, Rippe B. Acute reactive oxygen species (ROS)-dependent effects of IL-1beta, TNF-alpha, and IL-6 on the glomerular filtration barrier (GFB) in vivo. Am J Physiol. Renal Physiol. 2015;309:F800–F806.

    Article  CAS  PubMed  Google Scholar 

  27. Axelsson J, Mahmutovic I, Rippe A, Rippe B. Loss of size selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma. Am J Physiol Renal Physiol. 2009;297:F577–F582.

    Article  CAS  PubMed  Google Scholar 

  28. McCarthy ET, Sharma R, Sharma M, et al. TNF-alpha increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J Am Soc Nephrol. 1998;9:433–438.

    CAS  PubMed  Google Scholar 

  29. Tofik R, Sward P, Ekelund U, et al. Plasma pro-inflammatory cytokines, IgM-uria and cardiovascular events in patients with chest pain: a comparative study. Scand J Clin Lab Invest. 2015;75:638–645.

    Article  CAS  PubMed  Google Scholar 

  30. White SL, Polkinghorne KR, Cass A, Shaw JE, Atkins RC, Chadban SJ. Alcohol consumption and 5-year onset of chronic kidney disease: the AusDiab study. Nephrol Dial Transplant. 2009;24:2464–2472.

    Article  PubMed  Google Scholar 

  31. Schaeffner ES, Kurth T, de Jong PE, Glynn RJ, Buring JE, Gaziano JM. Alcohol consumption and the risk of renal dysfunction in apparently healthy men. Arch Int Med. 2005;165:1048–1053.

    Article  Google Scholar 

  32. Van Thiel DH, Gavaler JS, Little JM, Lester R. Alcohol: its effect on the kidney. Metabolism. 1977;26:857–866.

    Article  PubMed  Google Scholar 

  33. Walther L, de Bejczy A, Lof E, et al. Phosphatidylethanol is superior to carbohydrate-deficient transferrin and gamma-glutamyltransferase as an alcohol marker and is a reliable estimate of alcohol consumption level. Alcohol Clin Exp Res. 2015;39:2200–2208.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Sciences Lund, Gastroenterology and Hepatology, Faculty of Medicine, Lund University, Lund, Sweden

    Sara Bertilsson

  2. Department of Clinical Sciences Lund, Orthopaedics, Skane University Hospital, Lund University, Lund, Sweden

    Per Swärd

  3. Department of Clinical Sciences Lund, Psychiatry, Addiction Centre Malmö, Psychiatry Skane, Lund University, Lund, Sweden

    Anders Håkansson

  4. Department of Clinical Sciences Lund, Nephrology, Skane University Hospital, Lund University, Lund, Sweden

    Rafid Tofik & Bengt Rippe

  5. Digestive Disease Centre, Copenhagen University Hospital/Herlev, University of Copenhagen, 2730, Copenhagen, Denmark

    Evangelos Kalaitzakis

Authors
  1. Sara Bertilsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Per Swärd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anders Håkansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafid Tofik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bengt Rippe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Evangelos Kalaitzakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evangelos Kalaitzakis.

Ethics declarations

Conflict of interest

The authors disclose no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 30 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bertilsson, S., Swärd, P., Håkansson, A. et al. Microproteinuria Predicts Organ Failure in Patients Presenting with Acute Pancreatitis. Dig Dis Sci 61, 3592–3601 (2016). https://doi.org/10.1007/s10620-016-4335-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-016-4335-7

Keywords

Search

Navigation