Context: Diffused endothelial dysfunction in sepsis leads to an increase in systemic capillary permeability, the renal component manifesting as microalbuminuria. The degree of microalbuminuria correlates with the severity of the acute insult, the quantification of which may serve to predict sepsis and mortality in critically ill patients.
Aims: To evaluate whether the degree of microalbuminuria could differentiate patients with sepsis from those without and predict mortality in critically ill patients.
Settings and Design: Prospective, non-interventional study in a 20-bed Intensive Care Unit (ICU) of a tertiary care hospital.
Methods and Materials: After exclusions, between Jan-May2007, 94 consecutive adult patients were found eligible. Albumin-creatinine ratio (ACR, mg/g) was measured in urine samples collected on ICU admission (ACR1) and at 24 hours (ACR2).
Results: Patients were classified into two groups: those with sepsis, severe sepsis and septic shock (n = 30) and those without sepsis [patients without systemic inflammatory response syndrome (SIRS) and with SIRS due to noninfectious causes] (n = 64). In the sepsis group, median ACR1 [206.5 (IQR129.7-506.1)] was significantly higher compared to the non sepsis group [76.4 (IQR29-167.1)] (P = 0.0016, Mann Whitney). The receiver operating characteristics (ROC) curve analysis showed that at a cut off value 124 mg/g, ACR1 may be able to discriminate between patients with and without sepsis with a sensitivity of 80%, specificity of 64.1%, positive predictive value (PPV) of 51.1% and negative predictive value (NPV) of 87.3%. The median ACR2 [154 (IQR114.4-395.3)] was significantly higher (P = 0.004) in nonsurvivors (n = 13) as compared to survivors [50.8 (IQR 21.6-144.7)]. The ROC curve analysis revealed that ACR2 at a cut-off of 99.6 mg/g could predict ICU mortality with sensitivity of 85%, specificity of 68% with a NPV of 97% and PPV of 30%.
Conclusion: Absence of significant microalbuminuria on ICU admission is unlikely to be associated with sepsis. At 24 hours, absence of elevated levels of microalbuminuria is strongly predictive of ICU survival, equivalent to the time-tested APACHE II scores.
Angus DC, Linde-Zwirble WT, Lidicker J. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-10.
Todi S, Chatterjee S, Bhattacharyya M. Epidemiology of severe sepsis in India. Crit Care 2007;11:65.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
Wheeler AP, Steingrub J, Linde-Zwirble W, McCollam JS, Zeckel M. Prompt administration of drotrecogin alfa (activated) is associated with improved survival. Crit Care Med 2003;12:A120.
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-50.
Aird William C. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003;101:3765-77.
Gosling P. Microalbuminuria: A marker of systemic disease. Br J Hosp Med 1995;54:285-90.
Berton G, Citro T, Palmieri R, Petucco S, De Toni R, Palatini P. Albumin excretion rate increases during acute myocardial infarction and strongly predicts early mortality. Circulation 1997;96:3338-45.
De Gaudio AR, Spina R, Di Filippo A, Feri M. Glomerular permeability and trauma: A correlation between microalbuminuria and injury severity score. Crit Care Med 1999;27:2105-8.
De Gaudio AR, Adembri C, Grechi S, Novelli GP. Microalbuminuria as an early index of impairment of glomerular permeability in postoperative septic patients. Intensive Care Med 2000;26:1364-8.
Szakmany T, Molnar Z. Increased glomerular permeability and pulmonary dysfunction following major surgery: Correlation of microalbuminuria and PaO2/FiO2 ratio. Acta Anaesthesiol Scand 2004;48:704-10.
Yew WS, Pal SK. Correlation of microalbuminuria and outcome in patients with extensive burns. Br J Anaesth 2006;97:499-502.
Terao Y, Takada M, Tanabe T, Ando Y, Fukusaki M, Sumikawa K. Microalbuminuria is a prognostic predictor in aneurysmal subarachnoid hemorrhage. Intensive Care Med 2007;33:1000-6.
MacKinnon KL, Molnar Z, Lowe D, Watson ID, Shearer E. Use of microalbuminuria as a predictor of outcome in critically ill patients. Br J Anaesth 2000;84:239-41.
Abid O, Sun Q, Sugimoto K, Mercan D, Vincent JL. Predictive value of microalbuminuria in medical ICU patients: Results of a pilot study. Chest 2001;120:1984-8.
Gosling P, Brudney S, McGrath L, Riseboro S, Manji M. Mortality prediction at admission to intensive care: A comparison of microalbuminuria with acute physiology scores after 24 hours. Crit Care Med 2003;31:98-103.
Thorevska N, Sabahi R, Upadya A, Manthous C, Amoateng-Adjepong Y. Microalbuminuria in critically ill medical patients: Prevalence, predictors, and prognostic significance. Crit Care Med 2003;31:1075-81.
Gosling P, Czyz J, Nightingale P, Manji M. Microalbuminuria in the intensive care unit: Clinical correlates and association with outcomes in 431 patients. Crit Care Med 2006;34:2158-66.
Gopal S, Carr B, Nelson P. Does microalbuminuria predict illness severity in critically ill patients on the intensive care unit? A systematic review. Crit Care Med 2006;34:1805-10.
Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: What is useful? Crit Care Med 2006;22:503-19.
Boldt J, Muller M, Kuhn D, Linke LC, Hempelmann G. Circulating adhesion molecules in the critically ill: A comparison between trauma and sepsis patients. Intensive Care Med 1996;22:122-8.
Bossuyt PM, Reitsma JE, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD initiative. Clin Chem 2003;49:1-18.
Members of the American College of Chest Physicians, Society of Critical Care Medicine: American College of Chest Physicians-Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-75.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 2003;31:1250-6.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med 1985;13:818-29.
Jorge IF, Salluh P, Bozza T. Biomarkers of sepsis: Lost in translation? Crit Care Med 2008;36:2192-4.
Shawn CD, George S, Maryam T. Toward resolving the challenges of sepsis diagnosis. Clin Chem 2004;50:1-14.
Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: Clinical utility and limitations. Crit Care Med 2008;36:941-52.
Bakker AJ. Detection of microalbuminuria. Receiver operating characteristic curve analysis favors microalbuminuria-to-creatinine ratio over albumin concentration. Diabetes Care 1999;22:307-13.
Molnar Z, Szakmany T, Koszegi T, Tekeres M. Microalbuminuria and serum procalcitonin levels following oesophagectomy. Eur J Anaesthesiol 2000;17:464-5.
Dziedzic T, Slowik A, Szczudlik A. Urine albumin excretion in acute ischaemic stroke is related to serum interleukin-6. Clin Chem Lab Med 2004;42:182-5.
Singh A, Satchell SC, Neal CR, McKenzie EA, Tooke JE, Mathieson PW. Glomerular endothelial glycocalyx constitutes a barrier to protein permeability. J Am Soc Nephrol 2007;18:2885-93.
Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, et al. TNF-α induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol 2009;104:78-89.
Spapen HD, Diltoer MW, Nguyen DN, Hendriks I, Huygens LP. Effects of N-acetylcysteine on microalbuminuria and organ failure in acute severe sepsis. Chest 2005;127:1413-9.
Rinaldi S, Adembri C, Grechi S, De Gaudio R. Low dose hydrocortisone during severe sepsis: Effects on microalbuminuria. Crit Care Med 2006;34:2334-9.
Wincour PH, Marshall SM. Microalbuminuria biochemistry, epidemiology and clinical practice. Cambridge: Cambridge University Press; 1998.
Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, et al Microalbuminuria in the US population: Third national health and nutrition examination Survey. Am J Kidney Dis 2002;39:445-59.