Serum estradiol levels predict survival and acute kidney injury in patients with septic shock--a prospective study.

Jia-Yih Feng,Po-Yi Tsai,Edward Abraham,Kuan-Ting Liu,Cordula M. Stover,Kuang-Yao Yang,Yu-Chin Lee,Cheng-Yu Chen,Yu-Chun Chen

doi:10.1371/journal.pone.0097967

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.

Highlights

Sepsis and septic shock involve dysregulated inflammatory responses caused by interaction between the host immune system and microorganisms
From January 2008 to December 2011, patients admitted to the medical intensive care unit (ICU) and respiratory ICU were screened for the presence of septic shock associated with pneumonia
Patients who had underlying malignancy, autoimmune disorders, were taking sex hormone supplements, were less than 18 years old, were premenopausal women, had acute respiratory distress syndrome (ARDS) caused by non-pulmonary infection, and presented to ICUs with hypotension for more than 24 hours were excluded from enrollment

Summary

Introduction

Sepsis and septic shock involve dysregulated inflammatory responses caused by interaction between the host immune system and microorganisms. Despite recent progress in care, sepsis and septic shock remain associated with high morbidity and mortality [1], as well as diminished organ function or failure, including the kidneys, lungs, and bone marrow [2]. 60–70% develop acute kidney injury (AKI), which is associated with elevated in-hospital mortality rates that approach 50% [3,4,5]. RIFLE classifications were found to correlate well with disease severity and clinical outcomes, including mortality [4,7]. Sex hormones have been reported to have regulatory effects on immune responses. Limited clinical studies demonstrated the potential association between serum sex hormones levels and the occurrence and treatment outcomes of septic shock [13,14]. Information concerning the association between sex hormones and sepsis-related multi-organs dysfunctions are lacking

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