Serum Estradiol Levels Predict Survival and Acute Kidney Injury in Patients with Septic Shock- A Prospective Study

Abstract

Sex hormones have diverse immunomodulatory effects that may be involved in the pathogenesis of sepsis. However, the roles of serum sex hormones in predicting outcomes and the severity of organ dysfunction, especially acute kidney injury (AKI), in septic shock patients remains controversial. We prospectively enrolled 107 clinically diagnosed pneumonia-related septic shock patients and serum sex hormone levels were measured on the day of shock onset. The aim of the present study was to investigate the predictive values of serum sex hormones levels for 28-day mortality and organs dysfunction, especially AKI. Compared with survivors, serum levels of progesterone (p<0.001) and estradiol (p<0.001) were significantly elevated in non-survivors. In multivariate Cox regression analysis, serum level of estradiol >40 pg/mL (p = 0.047) and APACHE II score ≥25 (p = <0.001) were found to be independent predictors of day 28 mortality. Inclusion of estradiol levels further enhanced the ability of APACHE II scores to predict survival in patients with high mortality risk. A serum level of estradiol >40 pg/mL was also an independent predictor of concomitant AKI (p = 0.002) and correlated well with severity of renal dysfunction using RIFLE classification. Elevated serum estradiol levels also predicted the development of new AKI within 28 days of shock onset (p = 0.013). In conclusion, serum estradiol levels appear to have value in predicting 28-day mortality in septic shock patients. Increased serum estradiol levels are associated with higher severity of concomitant AKI and predict development of new AKI.

Systematic review regarding metabolic profiling for improved pathophysiological understanding of disease and outcome prediction in respiratory infections

“…Table 1 depicts the strong association between increased serum estradiol and progesterone levels and 28-day mortality in patients suffering from pneumonia-related septic shock, whereas serum testosterone levels are not noticeably different between survivors and non-survivors after a 28-day follow-up [ 67 ]. A prospective clinical study of elderly men who were free of cardiovascular disease at the time of blood sample collection, revealed a significant inverse association between dehydrotestosterone (DHT) and calculated free DHT levels with all-cause mortality during a follow-up period of 9 years, whereas total testosterone and calculated free testosterone showed no significant correlation with mortality [ 68 ].…”

Serum Estradiol Level at Intensive Care Unit Admission and Mortality in Critically Ill Patients

“…During stress, gonadal synthesis of estradiol is inhibited by Class I cytokines and tumor necrosis factor alpha, whereas there is an activation of the peripheral estradiol production by enzyme aromatase in adipose tissue, regardless of gender of the patients. [ 1 2 3 6 ] Estradiol causes changes in the immune response such as inhibition of the action of T-cells and activation of B-cell and macrophages inducing the production of interleukin 2 and interferon-α, mainly. [ 7 8 ]…”

“…Different studies in animal models have shown that changes in the immune response induced by estradiol produce an inflammatory response and modify the survival. [ 3 5 6 7 8 ] In humans, some authors have shown that, in clinical settings such as trauma or surgical patients, the increase in the serum level of estradiol was associated with increased severity of disease and mortality, regardless of the gender of patients, and was proposed as a tool for predicting mortality. [ 1 3 5 8 9 10 ] All this evidence has been documented in specific groups of patients and used different cutoffs of serum estradiol levels to predict mortality.…”

Time-dependent association of glucocorticoids with adverse outcome in community-acquired pneumonia: a 6-year prospective cohort study

“…Endogenous adrenocortical function is of prognostic value in critical illness and sepsis [7–14], of which community-acquired pneumonia (CAP) is a major source [15–17]. Morbidity in CAP is still high also, owing to higher risk for cardiovascular events [18, 19].…”

“…Morbidity in CAP is still high also, owing to higher risk for cardiovascular events [18, 19]. Researchers in multiple studies have investigated the adrenal steroid metabolism in relation to CAP-associated outcomes [14, 20–25]. In observational trials, researchers have reported increased admission cortisol levels to be independent predictors of disease severity and short-term mortality in patients across the spectrum of mild to severe CAP [20–24].…”