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 Table of Contents  
Year : 2018  |  Volume : 5  |  Issue : 4  |  Page : 267-278

Urine albumin/creatinine ratio as an early predictor of outcome in critically ill patients with sepsis

1 Department of Critical Care, Helwan University, Helwan, Egypt
2 Department of Internal Medicine, Assuit University, Assuit, Egypt
3 Department of Clinical Pathology, Helwan University, Helwan, Egypt

Date of Submission07-Mar-2018
Date of Acceptance16-Apr-2018
Date of Web Publication13-Dec-2018

Correspondence Address:
Mohammed A.M Saeed
28th El Dhaher Street, Cairo, 11211
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/roaic.roaic_14_18

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Background Many scoring systems have been developed for the prognosis and outcome prediction in sepsis, so trying to find a prognostic marker confirming the scoring systems results and predicting outcome is very important to improve patient’s outcome.
Objective This study aimed to evaluate the urinary albumin/creatinine ratio (ACR) as a prognostic marker in sepsis.
Patients and methods Forty adult patients with sepsis were included in a prospective observational study.
Patients with pre-existing chronic kidney disease or Diabetes mellitus were excluded. Clinical evaluation was done first and then urine spot samples were collected on admission and 24 hrs later for ACR1 and ACR2 estimation.
Acute physiology and chronic Health Evaluation (APACHE) IV score done on admission and sepsis related organ failure Assessment score, with the highest recorded score of their daily estimation, were considered.
The need for mechanical ventilation, inotropic and for vasoactive support, renal replacement therapy and in hospital mortality were also evaluated in our study.
Results The mean age of the patients was 63 (55–71) years and 29 (72.5%) were male. We found that the ACR2 is correlated with the sepsis related organ Failure assessment [14 (4.8–16.8) vs 5 (3–8), P=0.01] of the ACR measures, none of them were correlated with APACHE IV Score.
In patients who needed mechanical ventilation and inotropic and/or vasoactive support, ACR2 was higher [140 (125–207) and 151 (127–218) mg/gm, respectively] compared with those who did not need [65 (47–174) and 74 (54–162/mg/g], P=0.01 and 0.009.
All of the measured parameters were not related to the need of renal replacement therapy. Predictors of mortality were ACR1, ACR2, APACHE IV and increasing ACR.
Area under the curve for mortality prediction was largest for APACHE IV (0.90) and the ACR2 (0.88). ACR2 of 110.5 mg/g was 100%. Sensitive and 86% specific to predict mortality.
Conclusion Urinary ACR can be used as a simple test for prognosis and mortality prediction in sepsis cases.

Keywords: microalbuminuria, mortality, sepsis, urinary albumin–creatinine ratio

How to cite this article:
Saeed MA, Mahdy RE, Mohammed SA. Urine albumin/creatinine ratio as an early predictor of outcome in critically ill patients with sepsis. Res Opin Anesth Intensive Care 2018;5:267-78

How to cite this URL:
Saeed MA, Mahdy RE, Mohammed SA. Urine albumin/creatinine ratio as an early predictor of outcome in critically ill patients with sepsis. Res Opin Anesth Intensive Care [serial online] 2018 [cited 2020 Feb 20];5:267-78. Available from: http://www.roaic.eg.net/text.asp?2018/5/4/267/247399

  Introduction Top

Overall, 25% of the ICU cases and 1–2% of all hospitalized patients complain of sepsis. Sepsis causes more than 200 000 deaths each year in the USA [1].

A severe host defense response occurs in sepsis with triggering of potent inflammatory cascades leading to release of a plenty of proinflammatory and anti-inflammatory molecules into the circulation [2]. Endothelial dysfunction is a cornerstone in sepsis pathogenesis.

Systemic capillary leak is the end result of endothelial barrier integrity which is an early feature of sepsis [3].

This increased capillary permeability causes increased glomerular excretion of albumin in the urine [4].

Several studies have reported that microalbuminuria occurs early after severe inflammatory process and persists in more severe cases [5],[6],[7],[8].

Early prediction of mortality among critically ill patients with sepsis and early institution of intensive therapy are of great importance.

Many ICU scoring systems like the Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE IV, and Simplified Acute Physiology Score II to predict mortality are in current use.

A large number of variables derived from the patient’s history, examination, and initial laboratory data are required for these scoring systems.

A promising predictor of organ failure, vasopressor requirement and mortality prediction was found to be microalbuminuria, and it was shown to be better than APACHE II and Sepsis-related Organ Failure Assessment (SOFA) scores in some studies [9],[10],[11],[12],[13],[14].

Evaluation of the prognostic value of urinary albumin/creatinine ratio (ACR) in patients with sepsis is the aim of our study together also to compare this prognostic value with the APACHE IV and SOFA Scoring systems.

  Patients and methods Top

This is a prospective observational study that recruited all adult critically ill patients admitted to the General (medical/surgical) ICU Department, Faculty of Medicine, Helwan University, from January 2017 to December 2017. Patients included in the study were those diagnosed as having sepsis syndrome with the presence of SIRS based on the diagnostic criteria of 1992 ACCP/SCCM [15] and its update in 2001 international sepsis Definition Conference [16], exhibiting two or more of the following signs:
  1. Temperature of more than 38° or less than 36°C.
  2. Pulse rate of more than 90 beats/min.
  3. Respiratory rate of more than 20 breaths/min or hyperventilation with a PCO2 of less than 32 mmHg.
  4. White blood cell count of more than 12 000 or less than 4000/μl, or more than 10% immature cells.

The presence of infection was defined according to the clinical and microbiological criteria of the Centers for Disease Control and Prevention definitions [17] and was held as a gold standard.

It was determined by two independent experts who examined the patients daily for the first 48 h admission.

Patients excluded from the study were patients younger than 18 years old; patients with anuria or hematuria, with pre-existing chronic kidney disease, with diabetes mellitus, with proteinuria due to renal or post renal causes, and with urinary tract infection; and patients with ICU length of stay (LOS) less than 24 h.

The study protocol was approved by the Ethical Committee of Helwan University.

Patients included in the study were subjected to clinical evaluation including history, physical examination, routine laboratory investigations (capillary blood glucose, coagulation profile, arterial blood gases, liver function tests, kidney function tests, and serum electrolytes), and cultures from suspected sources of infection, including sputum, urine, etc., together with at least two blood cultures acquired from different venipunctures obtained before antibiotic administration. APACHE IV score was calculated in an integral score from web-based computed by applying the worst values of the measurements observed during 24 h following ICU admission with a maximum score of 286 [18]. The score was previously validated in patients with sepsis [19].

SOFA score is a scoring system used to determine the extent of organ dysfunction [20].

SOFA score was evaluated daily until ICU discharge or up to a total of 28 days. The highest recorded SOFA score was considered for statistical analysis.

Disease severity parameters that were studied included need for mechanical ventilation, need for inotropic and/or vasoactive support, and need for renal replacement therapy (RRT). Outcome was evaluated by ICU-LOS and the in-hospital mortality.

Urinary albumin creatinine ratio

Urine spot samples were collected at the time of ICU admission for ACR1 and 24 h following ICU admission for ACR2.

Immunoturbidimetric method is used for urinary microalbumin assaying and modified Kinetic Jaffe reaction (Dimension RXL Max; Dade Behring Inc., Deerfield, Illinois, USA) for urinary creatinine.

Change from ACR1 to ACR2 represents the trends of microalbuminuria. Difference between those values represents the ΔACR and is calculated as follows: ΔACR=ACR2−ACR1. When ΔACR is negative, it is defined as decreasing ACR, and when it is positive, it is defined as increasing ACR.

Statistical methods

Data were collected prospectively and coded before analysis using the statistical package of social science version 16.0 (SPSS Inc., Chicago, Illinois, USA).

Different dependent variables normal in distribution in relation to their independent variables were studied. Shapiro–Wilk’s test was done for normality for all variables, with a P value of 0.05 indicating normality together with Z-value of skewness and Kurtosis between −1.96 and +1.96 [21].

Our variables were found to be non-normally distributed. Continuous variables were accordingly expressed as median (Q1–Q3).

Categorical variables were expressed as frequency and proportion.

Nonparametric test (Mann–Whitney U-test) was used for comparison between two groups regarding quantitative variable. χ2-test was used for comparison between two groups regarding qualitative data.

Exact test was used instead when the expected frequency is less than 5. Spearman’s correlation coefficient test (r) was used to test a positive or negative relationship between the two variables. Receiver operator characteristic (ROC) analysis was done to define a cutoff value of a variable.

Sensitivity was estimated as true positive/(true positive+false negative), and specificity was estimated as true negative/(true negative+false positive). Results were statistically significant if P value is less than 0.05.

  Results Top

Sixty-five patients with sepsis were enrolled initially in our study in the period from January 2017 to December 2017.

Forty patients continued in the study, whereas 25 patients were excluded.

Eight patients had pre-existing chronic kidney disease, 13 had diabetes mellitus, and four patients died within 24 h of admission.

The 40 patients with sepsis included had an age ranging from 28 to 87 with a median (Q1–Q3) of 63 (55–71) years. The patients comprised 29 (72.5%) male and 11 (27.6%) female.

[Table 1] shows the source of infection in our patients’ population. The highest SOFA score was 7.0 (4.0–14.0), ranging from 1 to 17, and APACHE IV score recorded within first 24 h of ICU admission was 77.5 (58.8–98.0), ranging from 46 to 118.
Table 1 Source of sepsis

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In all, 23 (57.5%) of the 40 patients eligible in our study needed ventilator support, 20 (50%) needed inotropic and/or vasoactive support to maintain hemodynamics, and only seven (17.5%) needed RRT. LOS was 7.0 (5.0–9.0) days ranging from 3 to 19 days. Eighteen patients died with mortality rate of 45%, whereas 22 (55%) patients survived their ICU course ([Figure 1]).
Figure 1 Mortality rate in the study.

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Albumin/creatinine ratio measurements

ACR measured on admission (ACR1) was 113.2 (83.7–163.5), with a range from 29 to 229 mg/g, and the 24-h ACR (ACR2) was 136.4 (63.7–195.3), ranging from 21 to 255 mg/g ([Figure 2]). The ACR was decreased in 17 (42.5%) patients by 30 (22.4–39.7) mg/g and it was increased in 23 (57.5%) by 37.9 (26.4−59) ([Figure 3]).
Figure 2 ACR value on admission and 24 h later. ACR, albumin/creatinine ratio.

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Figure 3 ACR trend over the first 24 h. ACR, albumin/creatinine ratio.

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Albumin/creatinine ratio in relation to disease severity

The ACR1 was not significantly correlated with SOFA (r=0.236, P=0.172) or APACHE IV (r=0.188, P=0.28) scores, whereas the ACR2 was positively correlated with SOFA score (r=0.366, P=0.031) but not with APACHE IV score (r=0.286, P=0.096).

The SOFA score was significantly higher in patients with increased ACR trend at 14 (4.75–16.75) than in patients with stationary or declining trend at 5 (3–8) (P=0.01).

At the same time, there was no significant difference in APACHE IV between patients with increased ACR trend at 81.5 (58.8–101.3) and those with stationary or declining ACR trend at 66 (56–86) (P=0.3) ([Table 2]).
Table 2 Correlation between ACR1, ACR2, and SOFA and APACHE IV scores and their relation to the ACR trend

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ACR1 was not statistically different in patients who needed and those who did not need mechanical ventilation [115.7 (98.5–186.4) vs. 85 (73.8–143.4) respectively, P=0.09], whereas ACR2 was significantly higher in patients who required mechanical ventilation compared with those who did not need [129.7 (15.3–207.6) vs. 65.0 (47.0–174.1) respectively, P=0.011)] ([Table 3]).
Table 3 ACR1 and ACR2 in need of mechanical ventilation, inotropic and/or vasoactive support and RRT

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Considering the change in ACR, we found that the increase in ACR was a predictor of need of mechanical ventilation. Of the 23 patients with increased ACR, 18 (78.3%) needed mechanical ventilation, whereas five (21.7%) did not (P=0.003).

A similar relation was found between ACR1 and ACR2 and the need of inotropic and/or vasoactive support.

ACR1 was not significantly different in patients who needed and those who did not need inotropic and/or vasoactive support [114.5 (99.8−202.7) vs. 99.5 (73.0–137.8) respectively, P=0.06], whereas ACR2 was significantly higher in patients who needed inotropic and/or vasoactive support compared with those who did not need [150.5 (126.9–218.2) vs. 74.8 (53.9–161.8), respectively, P=0.009] ([Table 3]). With the change in ACR, we reached to the conclusion that the increase in ACR was a predictor of need of inotropic and/or vasoactive support.

Of the 23 patients with increased ACR, 16 (69.6%) patients needed inotropic and/or vasoactive support, whereas seven (30.4%) patients did not (P = 0.01).

Neither ACR1 nor ACR2 was significantly related to the need for RRT in our patients.

ACR1 was 113.2 (98.5–142.0) versus 115.7 (80.9–176.0) for those who needed and did not need RRT, respectively (P=0.9) and ACR2 was 139.7 (123.7–166.7) versus 135 (57.4–196.0), respectively (P=0.58) ([Table 3]).

The increase in ACR over time was not significantly associated with the need for RRT.

Of the 23 patients with increased ACR, six (26.1%) patients needed RRT, whereas 17 (73.9%) patients did not (P=0.2).

Albumin/creatinine ratio and outcome

The ACR1 and ACR2 were significantly positively correlated with ICU-LOS (r=0.5, P=0.007 for ACR1 and r=0.4, P=0.05 for ACR2) ([Figure 4]).
Figure 4 Correlation between ACR and ICU-LOS. ACR, albumin/creatinine ratio; LOS, length of stay.

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Both ACR1 and ACR2 were a significant predictor for mortality in our patient population.

ACR1 and ACR2 were 121.3 (103.7–189.7) and 193.0 (137.8–219.9) mg/g, respectively, in nonsurvivors compared with 90.8 (72.3–128.4) and 69.1 (49.3–132.5) mg/g, respectively, for survivors (P=0.009 and <0.001 for ACR1 and ACR2, respectively) ([Figure 5] and [Figure 6]).
Figure 5 ACR1 and survival. ACR, albumin/creatinine ratio.

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Figure 6 ACR2 and survival. ACR, albumin/creatinine ratio.

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The increase in ACR after 24 h compared with admission ACR was associated with increased mortality.

Sixteen (88.9%) of the 18 nonsurvivors had an increased ACR, whereas only two (11.1%) had a stationary or decreased ACR.

Of the 22 survivors, 15 (68.2%) had a stationary or decreased ACR, whereas only seven (31.8%) had an increased ACR (P=0.001). The use of increased ACR to predict mortality had 89% sensitivity and 68% specificity.

ROC curve was examined for the use of APACHE IV and ACR concentrations as a predictor of ICU mortality ([Figure 7]). The area under the ROC curve (AUC) for APACHE IV to predict ICU mortality was the highest of the examined parameters (0.90).
Figure 7 Receiver operator characteristic curve for APACHE IV, ACR1, and ACR2 for mortality prediction. ACR, albumin/creatinine ratio; APACHE IV, Acute Physiology and Chronic Health Evaluation IV.

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The optimal cutoff value for APACHE IV to predict ICU mortality was 72.5 that had a sensitivity of 100% and a specificity of 80% for ICU mortality prediction, whereas an ACR2 cutoff of 110.5 mg/g was 100% sensitive and 86.2% specific ([Table 4]).
Table 4 AUC, their significance, cutoff values, and the sensitivity and specificity for mortality prediction

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The different cutoff values and their sensitivity and specificity for mortality prediction are seen in [Table 4].

  Discussion Top

Sepsis is not only a great health problem but also an important socioeconomic challenge worldwide. Patients’ living quality is lowered and mortality increased significantly by sepsis [1]. Identification of sepsis prognosis and outcome prediction is of great importance in the prediction of prognosis in ICU through the APACHE scores [18], which predict mortality, and the SOFA score [20], which predict morbidity.

All scoring systems are based on several physiological indices and chemical analyses, and at the same time, difficulty in estimation and several drawbacks and limitations have been shown in these scoring systems [22].

Microalbuminuria is a beneficial biomarker of disease severity and mortality prediction [9],[10] and indirectly quantifies the changes in systemic vascular permeability [4], especially in critically ill patients with severe endothelial and renal involvement. This was shown in several clinical trials. At the same time, microalbuminuria can be used as a significant prognostic marker of morbidity and mortality [14]. Within hours of an inflammatory insult, the level of microalbuminuria starts to increase against delayed increases in levels of many other mediators [23].

We aimed to evaluate in our study the prognostic value of urinary ACR in sepsis and to compare the prognostic value with the APACHE IV and SOFA scoring systems in the ICU.

Ours is a prospective study that included forty critically ill patients with sepsis syndrome admitted to the general ICU.

All were subjected to the assaying of urinary ACR on admission (ACR1) and 24 h/later (ACR2). APACHE IV score (in the first 24 h of ICU admission) and the highest SOFA score on daily basis measurements were recorded.

We excluded patients with diabetes mellitus and chronic kidney disease as they are common factors causing increased ACR.

Endothelial dysfunction arises from the effects of cytokines and other inflammation mediators released during the intense inflammatory responses, leading to systemic increase in capillary permeability, and this characterizes the sepsis syndrome [2]. Acute respiratory distress syndrome (ARDS) can occur secondary to increased capillary permeability in the pulmonary circulation [24] and sepsis-induced hypotension in systemic circulation [25], and increased amounts of albumin to escape into the glomerular ultrafiltrate this occurs in renal circulation, increased excretion of albumin in urine occurs because the tubular reabsorptive mechanism for albumin from the ultrafiltrate is exceeded above its threshold capacity [26].

Development of ARDS, hemodynamic compromise and acute kidney injury was supposed to relate to microalbuminuria as a marker of increased permeability [26], Basu et al. [27] accordingly evaluated the use of mechanical ventilation, inotropic and/or vasoactive support, and RRT as severity indicators.

In our study, no significant correlation was found between ACR1 on admission and either SOFA or APACHE IV scores, whereas ACR2 obtained 24 h later was significantly correlated with SOFA score but was not statistically significantly correlated with APACHE IV score. Moreover, SOFA but not APACHE IV score is higher in patients with an increasing trend of ACR.

Basu et al. [27] who studied the medical surgical critically ill patients found that ACR1 and 24 after admission was correlated with APACHE II score.

Many studies done on medical cases only found that increasing microalbuminuria had a good sensitivity and specificity to predict the occurrence of multiorgan failure.

Increasing microalbuminuria levels were correlated with a high APACHE II score [10]. Patients with increased trend of ACR over their ICU stay were found to have higher ACPACHE II and SOFA scores compared with patients with stationary or declining ACR level [10].

Increasing ACR is positively correlated with an increasing SOFA score in 55 postoperative patients with sepsis, and this was reported by de Gaudio et al. [5].

Moreover, de Gaudio et al. [28] who studied 40 patients with trauma reported that the degree of increase in microalbuminuria over the first 24 h following trauma was related to the severity of trauma.

In our study, ACR2 and the ΔACR and not the ACR1 were associated with a higher incidence of need of mechanical ventilation and need of inotropic and/or vasoactive support.

ACR is inversely associated with the PaO2/FiO2 ratio in post-trauma patients and was associated with significantly more direction of mechanical ventilation in patients with initially normal lung function, and this was found in many studies [29].

ACR done 8 h after admission was predictive of the occurrence of ARDS and this was found by Pallister et al. [30].

ACR on admission and 6 h later was higher in patients with vasoactive and inotropic support and strongly correlated with ventilator days; this was also concluded by many authors and studies [13].

Patients with increasing ACR had higher incidence of acute respiratory failure and multi organ dysfunction syndrome (MODS) compared with those with decreasing or stationary ACR; this was found by Abid et al. [10].

An inverse relationship between the degree of change in microalbuminuria and the lowest PaO2/FiO2 ratio; this also was found by Basu et al. [27].

Another study conducted on 25 patients with sepsis contradicted these results and showed that ACR did not correlate with extravascular lung water and PaO2/FiO2 ratio, reaching to the conclusion that microalbuminuria does not reflect increased systemic capillary permeability in septic shock [31], as they supposed that the pulmonary vascular permeability is not the only determinant of the extravascular lung water and that volume status, cardiac function, and severity of lung injury contribute to extravascular lung water. At the same time, the authors in that study criticized their conclusion by the very low serum albumin in their patient population that may influence urinary albumin excretion [31].

Seven (17.5%) patients in our study needed RRT, whereas 33 (82.5%) patients did not need RRT.

No relationship was found between ACR either on admission or 24 h late or even ΔACR and the need for RRT.

Zhang et al. [32] in patients with sepsis with normal kidney function found that ACR on second day of admission was higher in patients who developed acute kidney injury, and they also found that ACR on second day of admission 43 mg/g was 91.7% sensitive and 79.2% specific for predicting acute kidney injury in patients with sepsis [32].

Moreover, ACR on admission correlated with serum creatinine, and this was found by Gosling et al. [12], but they did not comment on the need for RRT.

Increasing microalbuminuria had a good sensitivity and specificity to predict development of acute renal failure, and this was found in a study based on medical cases only [10].

The presence of higher ACR on admission to ICU may be an early indicator of acute kidney injury in sepsis, and this was found in a study done by Basu et al. [27]. These findings were supported by an increase in urinary albumin excretion and was correlated with increases in systemic capillary leakage [33].

The kidneys receive ∼25% of the cardiac output, so small changes in glomerular permeability will lead to change in microalbuminburia, and so the kidneys are sensitive to permeability change [33].

Higher levels of microalbuminuria in sepsis are related to the defects in the glycocalyx layer of the fenestrated glomerular capillaries, induced by the inflammatory process. This was postulated by some authors, as this glycocalyx layer acts as a barrier to protein permeability, and degradation of this layer increases the passage of albumin across the glomerulus [34]. These pathologic changes occurring in the kidneys can be explained by the impairment of kidney function that occurs when ACR is increased. The lack of relation between the ACR and need for RRT study can be attributed to the small sample size and small number of patients who needed RRT (only seven patients). Compared with other studies, also we did not follow up and evaluate the development of acute kidney injury that did not reach the level of RRT, so we may lose an association between ACR and kidney involvement.

ICU-LOS of was on average in our study at 7.0 (5.0–9.0) days.

Positive correlation was found between ACR on admission and 24 h later and the ICU-LOS.

ACR values positively correlate with ICU-LOS, and this was found by Gosling and colleagues, and Zhang and colleagues. ACR was measured on admission and 6 h later in the study by Gosling and colleagues.

Patients with ACR more than or equal to 100 mg/g stayed for 5 days longer in the ICU, and this was found by Thorecvska et al. [11], among survivors of critically ill patients.

Correlation between ACR and ICU-LOS reflects their association with disease severity.

Predictors of mortality in our study were APACHE IV, ACR1, and ACR2.

Regarding ROC analysis, the AUC was highest for APACHE IV score (0.905), then ACR2 (0.876), and then ACR1 (0.755).

APACHE IV score of 72.5 have 100% sensitivity and 80% specificity, ACR1 of 86.3 mg/g to have 100% sensitivity and 50% specificity, and ACR2 of 110.5 mg/g have 100% sensitivity and 86.12% specificity to predict mortality.

Trend of ACR over time is a predictor of mortality with higher mortality with increase in ACR2 compared with ACR1; increase in ACR is associated with 89% sensitivity and 68% specificity for detection of mortality in patients with sepsis.

Gopal et al. [14] found that ACR may hold promise as a predictor of mortality. ROC curve and AUC found by Bhadade et al. [35], for prediction of mortality were highest for ACR2 (0.943) and changes in ACR overtime (0.943), followed by APACHE II (0.835), SOFA (0.788) and ACR1 (0.725).ACR2 is as good as APACHE II for prediction of mortality, and this was concluded by Basu and colleagues [27],[36].

ACR2 4 h after admission of 99.6 mg/g had sensitivity of 85% and specificity of 68%; this was also found by Basu et al. [27]. Moreover, he found absence of microabluminuria is a predictor of survival [27].

Similar results were found by Gosling et al. [12] in surgical trauma and burn patients but not medical patients.

In another study on surgical patients, ACR assayed on ICU admission was able to significantly differentiate survivors from nonsurvivors [6].

In the subgroup of surgical and trauma patients, Gosling et al. [12] found that ACR more than 5.9 mg/mmol (52.5 mg/g) predicted mortality with 100% sensitivity and 59% specificity, but in medical patients, they did not show any difference in ACR between survivors and nonsurvivors.

Another study done by Gosling et al. [13] reached to the conclusion that in both medical and surgical patients who died in the ICU, the median ACR failed to decrease significantly 6 h following admission.

Thorevska et al. [11], who studied 104 mixed patients, found that ACR value more than or equal to 100 mg/g on admission were 2.7 times likely to die compared with those with ACR less than 100, and they concluded that ACR had similar predictive value of APACHE II score as an independent predictor of mortality.

Many other studies like our study showed higher mortality among patient with increasing ACR levels than those with stationary or declining values [10],[11],[32].

APACHE IV score has performed better than ACR2 and ΔACR in our study as the AUC was higher for APACHE IV.

ACR2 as a predictor of mortality can be attributed to the presence of on-going inflammatory processes among those who died, with higher levels of ACR2 among them. In contrast, lower levels of ACR2 indicate a decrease in the inflammatory activity and explain improved survival. ΔACR has the ability of prediction of mortality where an increasing trend predicts a poor outcome. Decrease in the inflammatory processes leads to decrease in levels of ACR within 24 h of ICU admission as a result of treatment.

Early treatment might help in protection of the glycocalyx layer and prevent rise in capillary permeability [34]. Microalbuminuria has a role in checking the effect of treatment based on the observations [35].

ACR change overtime carries a great importance than depending on one measure this was also explained by the presence of chronic microalbuminuria with some diseases as diabetic or hypertensive nephropathy even if not previously diagnosed.

Although there was presence of significant values of APACHE IV and ACR2, no correlation was found between them in our study owing to the small sample size. The small sample size limits our study. Two measures of the ACR were considered on admission and 24 h later; however, other measures in between can be beneficial. Mechanical ventilation and RRT are indicators for ARDS and acute kidney injury, respectively. Estimation of the deterioration in PaO2/FiO2 ratio and the serum creatinine was not included in our study, so we might miss the association between ACR and some degrees of ARDS and acute kidney injury.

  Conclusion Top

Urinary ACR is a simple, rapid, noninvasive, inexpensive, and early to perform and interpret test for early diagnosis and prediction of mortality in patients with sepsis.

Late ACR after 24 h from ICU admissions and ACR trend overtime are more important than earlier admission ACR. Measurement of ACR on admission to ICU and 24 h later together with conventional illness severity scores can provide more informative data on patient outcome.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2], [Table 3], [Table 4]

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