Korean J Crit Care Med.  2017 May;32(2):142-153. 10.4266/kjccm.2017.00094.

Implications of Plasma Renin Activity and Plasma Aldosterone Concentration in Critically Ill Patients with Septic Shock

• Chung KS
• Song JH
• Jung WJ
• Kim YS
• Kim SK
• Chang J
• Park MS

• KMID: 2384039
• DOI: http://doi.org/10.4266/kjccm.2017.00094

Abstract

BACKGROUND
The renin-angiotensin-aldosterone system is closely associated with volume status and vascular tone in septic shock. The present study aimed to assess whether plasma renin activity (PRA) and plasma aldosterone concentration (PAC) measurements compared with conventional severity indicators are associated with mortality in patients with septic shock.
METHODS
We evaluated 105 patients who were admitted for septic shock. Plasma levels of the biomarkers PRA and PAC, the PAC/PRA ratio, C-reactive protein (CRP) level, and cortisol level on days 1, 3, and 7 were serially measured. During the intensive care unit stay, relevant clinical information and laboratory results were recorded.
RESULTS
Patients were divided into two groups according to 28-day mortality: survivors (n = 59) and non-survivors (n = 46). The survivor group showed lower PRA, PAC, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score than did the non-survivor group (all P < 0.05). The SOFA score was positively correlated with PRA (r = 0.373, P < 0.001) and PAC (r = 0.316, P = 0.001). According to receiver operating characteristic analysis, the areas under the curve of PRA and PAC to predict 28-day mortality were 0.69 (95% confidence interval [CI], 0.58 to 0.79; P = 0.001) and 0.67 (95% CI, 0.56 to 0.77; P = 0.003), respectively, similar to the APACHE II scores and SOFA scores. In particular, the group with PRA value ≥3.5 ng ml⁻¹ h⁻¹ on day 1 showed significantly greater mortality than did the group with PRA value <3.5 ng ml⁻¹ h⁻¹ (log-rank test, P < 0.001). According to multivariate analysis, SOFA score (hazard ratio, 1.11; 95% CI, 1.01 to 1.22), PRA value ≥3.5 ng ml⁻¹ h⁻¹ (hazard ratio, 3.25; 95% CI, 1.60 to 6.60), previous history of cancer (hazard ratio, 3.44; 95% CI, 1.72 to 6.90), and coronary arterial occlusive disease (hazard ratio, 2.99; 95% CI, 1.26 to 7.08) were predictors of 28-day mortality.
CONCLUSIONS
Elevated PRA is a useful biomarker to stratify the risk of critically ill patients with septic shock and is a prognostic predictor of 28-day mortality.

Keyword

aldosterone; mortality; renin; shock, septic

MeSH Terms

Aldosterone*
APACHE
Arterial Occlusive Diseases
Biomarkers
C-Reactive Protein
Critical Illness*
Humans
Hydrocortisone
Intensive Care Units
Mortality
Multivariate Analysis
Plasma*
Renin*
Renin-Angiotensin System
ROC Curve
Shock, Septic*
Survivors
Aldosterone
Biomarkers
C-Reactive Protein
Hydrocortisone
Renin

Figure

• 

  Figure 1. Flow chart of inclusion and exclusion of patients in the study. A total of 140 patients were enrolled between August and December 2008, and 105 patients were included in the analysis. Patients without available renin and aldosterone measurements (n = 2), those using an angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) (n = 12), those using an aldosterone antagonist (n = 5), those using steroids (≥15 mg/d) (n = 12), and those who had previous usual hemodialysis (n = 4) within 7 days were excluded. ICU: intensive care unit.

• 

  Figure 2. Time courses of PRA and PACs in non-survivors versus survivors. Levels of PRA (A) and PACs (B) were measured on days 1, 3, and 7 after admission. The circles and bars indicate the mean values and SEM, respectively. Significant differences between nonsurvivors and survivors are indicated by an asterisk (*P < 0.05, survivors versus non-survivors on each day). PRA: plasma renin activity; PAC: plasma aldosterone concentration; SEM: standard error of the mean.

• 

  Figure 3. Correlations between PRA or PAC, SOFA score, and APACHE II score on day 1. The PRA levels correlated with better with APACHE II score (A) or SOFA score (B) than the PAC levels (C, D) although there were weak correlations. The open circles indicate survivors, and the solid circles indicate non-survivors. APACHE: Acute Physiologic and Chronic Health Evaluation; PRA: plasma renin activity; SOFA: Sequential Organ Failure Assessment; PAC: plasma aldosterone concentration.

• 

  Figure 4. Receiver operating characteristic curves for PRA and PAC on day 1 for predicting 28-day mortality. The prognostic accuracy of PRA and PAC was not inferior to that of the APACHE II and SOFA scores. APACHE: Acute Physiologic and Chronic Health Evaluation; AUC: area under the curve; CI: confidence interval; SOFA: Sequential Organ Failure Assessment; PRA: plasma renin activity; PAC: plasma aldosterone concentration.

• 

  Figure 5. Kaplan-Meier survival curves for 28 days according to PRA. The cutoff value was the optimal cutoff limit that predicted 28-day mortality (PRA <3.5 ng/ml/h or ≥3.5 ng/ml/h). PRA: plasma renin activity; ICU: intensive care unit.

Reference

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