Microalbuminuria: A novel biomarker of sepsis

Abstract

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-May 2007, 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.

Keywords: Capillary permeability; critically ill; intensive care units; microalbuminuria; mortality; sepsis.

Figure 1

Box whisker plots comparing albumin:creatinine ratio (ACR) at ICU admission (ACR1), between patients with sepsis and without sepsis. Significant difference was found between the two groups (P = 0.0016). Open squares indicate outliers while the closed circles indicate extreme values. Similar difference was found in the ∆ ACR values of the patients with and without sepsis (P = 0.0048).

Figure 2

Comparison of Receiver Operating Characteristic (ROC) curves of ACR1 (straight line), ACR2 (dashed line) and the change of ACR2 from ACR1 (∆ ACR, dotted line) to discriminate between patients with and without sepsis admitted to intensive care unit. Of the three, ACR1 had the highest area under the curve.

Figure 3

Change in urine albumin on intensive care unit admission (albumin-creatinine ratio [ACR] 1) and after 24 hours (ACR 2) in survivors (solid line) and nonsurvivors (dashed line) (Wilcoxon's signed rank test).