Abstract
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Objective
Sepsis is a leading cause of acute kidney injury (sepsis-associated acute kidney injury, SA-AKI) and is associated with multiorgan failure, cardiovascular events, and increased mortality. While research has generally focused on critically ill patients in intensive care units (ICUs), most sepsis cases are managed outside the ICU. This study investigated renal dysfunction as an early risk marker in patients presenting to the emergency department (ED) with severe infection and at risk for early sepsis.
-
Methods
This post hoc analysis of patients presenting to the ED used data from the Acutelines cohort (2020–2023). Kaplan-Meier curves and univariable and multivariable Cox regression analyses were performed to assess the association between AKI and all-cause mortality, as well as in-hospital mortality and cardiovascular death, adjusting for potential confounders.
-
Results
In total, 2,045 patients presented with sepsis at the ED, of whom 246 (12%) had AKI. The overall mortality rate was 25% over a median follow-up of 346 days. AKI was associated with higher all-cause mortality (38% vs. 26% P<0.001). After adjustment for sex, age, comorbidities, and sepsis severity, AKI remained independently associated with all-cause mortality (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.14–1.82; P=0.003), in-hospital mortality (HR, 1.65; 95% CI, 1.16–2.34; P=0.006), and cardiovascular death (HR, 2.50; 95% CI, 1.39–4.48; P=0.001). Similar outcomes were observed in a subanalysis excluding ICU patients.
-
Conclusion
SA-AKI at ED presentation is independently associated with increased all-cause, in-hospital, and cardiovascular mortality. These findings underscore the need for earlier recognition across care settings and the implementation of structured follow-up to improve patient outcomes.
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Keywords: Acute kidney injury; Sepsis; Emergency department; Mortality; Survival
Capsule Summary
What is already known
Sepsis is a leading cause of acute kidney injury (sepsis-associated acute kidney injury, SA-AKI), a condition strongly associated with multiorgan failure, cardiovascular complications, and increased mortality. The detrimental impact of SA-AKI has been well characterized among critically ill patients in intensive care units (ICUs). However, more than half of sepsis cases are managed outside the ICU.
What is new in the current study
This study provides a comprehensive evaluation of SA-AKI identified at the time of emergency department presentation, a critical early point in the hospital course. Our findings demonstrate that early SA-AKI is independently associated with all-cause, in-hospital, and cardiovascular mortality. The study highlights the importance of recognizing and managing SA-AKI from the moment of hospital entry and offers practical implications for improving early care.
INTRODUCTION
Sepsis is the most prevalent cause of acute kidney injury (AKI), accounting for approximately half of all AKI cases [
1,
2]. The development of AKI in the context of sepsis, commonly termed sepsis-associated AKI (SA-AKI), results from a combination of pathophysiological mechanisms including systemic inflammation, tubular injury, endothelial dysfunction, and microvascular disturbances [
3]. SA-AKI is associated with higher mortality, increased risk of chronic kidney disease, and cardiovascular complications [
4,
5]. While these detrimental effects of AKI have been extensively described in critically ill patients admitted to intensive care units (ICUs) [
6,
7], up to 50%$–88% of individuals with sepsis are managed outside the ICU [
8,
9]. Consequently, existing data on SA-AKI outcomes primarily reflect preselected populations with advanced disease, leading to underrepresentation and limited understanding of SA-AKI across the broader clinical spectrum.
In this study, we aimed to determine whether SA-AKI identified at the ED is associated with increased mortality risk and deserves greater recognition in emergency and post-acute care. By focusing on the ED population, we capture SA-AKI at the earliest stage of the hospital trajectory, providing a clearer perspective on its clinical relevance across diverse care settings.
METHODS
Ethics statement
The Acutelines cohort study was approved by the medical ethics committee of the University Medical Center Groningen and registered at the ClinicalTrials.gov (identifier: NCT04615065) [
10]. Further details regarding the Acutelines protocol have been published elsewhere [
11]. The study protocol was additionally approved by the Central Ethical Consent Commission of the UMCG (2023/17226). All study procedures adhered to the principles of the Declaration of Helsinki. Participants were asked to provide written informed consent; when not possible, consent was obtained by proxy.
This cohort study is a retrospective analysis of prospectively collected data from September 2020 to January 2023 within the Acutelines cohort. Acutelines is a multidisciplinary, hospital-based prospective data and biobank initiative at the emergency department (ED) of the University Medical Center Groningen, a tertiary care teaching hospital in the Netherlands [
10,
11].
Adult patients presenting to the ED with sepsis and enrolled in Acutelines were screened for inclusion. To assess the impact of SA-AKI in a clinically relevant ED population, we included patients with early sepsis, defined as those presenting with a severe infection at risk of developing sepsis according to either the Sepsis-2 (systemic inflammatory response syndrome [SIRS] ≥2) or Sepsis-3 (quick Sequential Organ Failure Assessment [qSOFA] ≥2) criteria [
12]. The presence and site of infection were determined by an expert adjudication committee from Acutelines [
10], following the US Centers for Disease Control and Prevention (CDC) consensus definitions [
13]. Patients without a confirmed infection, as determined by adjudication, were excluded.
The primary outcome was all-cause mortality. Mortality data were obtained from electronic health records and municipal registries for all included patients. Cause of death was defined according to the International Classification of Diseases, 10th Revision [
14]. Two medical experts independently assessed the cause of death while blinded to study outcomes; a third expert resolved any disagreements. Consistent with previous mortality studies, causes of death were categorized as cardiovascular, respiratory, infectious, malignant, other, or unknown [
15,
16].
AKI was defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria [
17]. Baseline plasma creatinine was determined by averaging all available measurements obtained during the 12 months preceding ED admission. Urine output was not used as a diagnostic criterion because it is not routinely monitored in the ED setting. Due to limited sample size, AKI grades 2 and 3 were combined for the analyses.
The Charlson Comorbidity Index (CCI) quantifies comorbidity burden using a weighted score to estimate mortality risk [
18]. The National Early Warning Score 2 (NEWS2) is a clinical assessment tool used to evaluate illness severity and identify clinical deterioration [
19].
All statistical analyses were conducted using IBM SPSS ver. 28 (IBM Corp). Graphical visualizations were produced using GraphPad Prism ver. 7.03 (Dotmatics). Descriptive analyses employed the t-test for normally distributed variables and the Mann-Whitney U-test for non-normally distributed data. Because follow-up durations varied across patients, median (interquartile range, IQR) follow-up times were reported for both all-cause and cardiovascular mortality. In-hospital follow-up corresponded to length of stay, with death considered at discharge. Missing data were addressed through multiple imputation using chained equations in five iterations after initial model specification (
Suppl. 1). Kaplan-Meier analyses and log-rank tests were used to compare all-cause mortality, in-hospital mortality, and cardiovascular death between early sepsis patients with and without AKI. Cox regression analyses were performed to evaluate the association between AKI and these outcomes. Associations were tested first in univariable models and subsequently in multivariable models adjusted for potential confounders, including sex, age, comorbidities, and sepsis severity indicators: Glasgow Coma Scale (GCS), heart rate at triage, temperature, systolic blood pressure, respiratory rate, symptoms of respiratory failure, leukocyte count, hemoglobin, and platelet count at ED admission. Model stability was assessed using sensitivity analyses for all-cause mortality (
Suppl. 2). Stratified analyses were performed for patients requiring ICU admission. Competing risks analyses using the Gray test were applied to estimate cumulative cause-specific mortality. A significance threshold of α=0.05 was used for all statistical tests.
To satisfy the proportional hazards assumption, leukocyte count was natural log-transformed, hemoglobin was categorized as <7.5 or ≥7.5 mmol/L, the CCI was categorized by IQR, and GCS was categorized as alert (score, 14–15) or not alert (score <14). Because of potential collinearity between oxygen saturation (SpO2) and oxygen supplementation at the ED, a composite variable termed “symptoms of respiratory failure” was created, defined as either receiving oxygen supplementation in the ED or having SpO2 <93%. Notably, oxygen supplementation is not routinely administered in the Dutch healthcare setting and is reserved for patients with clear clinical indications.
RESULTS
Population
From September 2020 to January 2023, a total of 2,045 patients with early sepsis were included in the study (
Suppl. 3). Baseline characteristics are presented in
Table 1. Among these patients, 246 (12.0%) met the KDIGO criteria for AKI, of whom 154 (62.6%) had grade 1 AKI and 92 (37.4%) had grade 2 or 3 AKI. Patients with SA-AKI had a greater comorbidity burden, including higher rates of diabetes mellitus (31.3% vs. 20.6%, P<0.001) and preexisting kidney disease (n=201; 38% vs. 26%, P<0.001). The CCI distribution was similar between groups except for the highest quartile, which was more common among SA-AKI patients (23.6% vs. 17.6%, P=0.02). Baseline plasma creatinine concentrations were also higher in SA-AKI patients compared with those without AKI (98 µmol/L vs. 84 µmol/L, P<0.001). The primary site of infection in the overall study population was the pulmonary tract (46%), followed by the urogenital tract (18%) (
Suppl. 4). SA-AKI patients presented more severely ill at the ED, as indicated by a higher NEWS2 median score (5 vs. 4, P<0.001). Although SA-AKI patients were more frequently admitted to the ICU (24.0% vs. 7.6%, P<0.001), most were managed on general wards (
Table 2).
During a median follow-up of 346 days (IQR, 155–581 days), the all-cause mortality rate in the study population was 24.7% (n=505). Mortality was higher in SA-AKI patients than in those without AKI (37.8% vs. 22.9%, P<0.001) (
Fig. 1). This corresponded to a crude hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.55–2.43; P<0.001) and remained statistically significant after adjusting for potential confounders—age, sex, comorbidities, and sepsis severity—resulting in an adjusted HR of 1.44 (95% CI, 1.14–1.82; P=0.003) (
Table 3). The crude model results are available in the
Suppl. 5–
7. Sensitivity analyses produced consistent findings (adjusted HR, 1.40; 95% CI, 1.10–1.79; P=0.01) (
Suppl. 6).
The median length of hospital stay was 6 days (IQR, 4–11 days). The overall in-hospital mortality rate was 8% (n=168) and was higher among SA-AKI patients than those without AKI (20% vs. 7%, P<0.001) (
Fig. 1). This corresponded to a crude HR of 1.89 (95% CI, 1.36–2.65; P<0.001) for in-hospital mortality, which remained significant after adjustment for potential confounders (adjusted HR, 1.65; 95% CI, 1.16–2.34; P=0.006).
Causes of death were determined through comprehensive review of electronic health records and municipal registry data. Infection-related deaths predominated during the early phase, whereas cardiovascular- and malignancy-related deaths increased over time and became the leading long-term causes (
Suppl. 8). Cardiovascular mortality was significantly higher among SA-AKI patients than those without AKI (19% vs. 11%, P=0.03) (
Table 2,
Fig. 1C). Conversely, malignancy-related deaths were more frequent among patients without SA-AKI (38% vs. 19%, P<0.001). Other causes of death did not differ significantly between groups. Cumulative incidence curves demonstrated a higher proportion of cardiovascular deaths among SA-AKI patients compared with those without AKI (P=0.022), with a crude HR of 3.21 (95% CI, 1.84–5.61; P<0.001) and an adjusted HR of 2.50 (95% CI, 1.39–4.48; P=0.001).
Greater AKI severity (KDIGO grades 2–3) was independently associated with higher all-cause mortality (adjusted HR, 1.96; 95% CI, 1.40–2.74; P<0.001) and cardiovascular mortality (adjusted HR, 3.77; 95% CI, 1.79–7.96; P<0.001), but not with in-hospital mortality (adjusted HR, 1.59; 95% CI, 0.98–2.60; P=0.06) (
Table 4,
Fig. 2). Interestingly, less severe AKI (KDIGO grade 1) was independently associated with in-hospital mortality (adjusted HR, 1.69; 95% CI, 1.10–2.58; P=0.02), but not with all-cause mortality (adjusted HR, 1.20; 95% CI, 0.89–1.63; P=0.23) or cardiovascular death (adjusted HR, 1.81; 95% CI, 0.83–3.93; P=0.13).
A total of 196 patients (10%) with early sepsis were admitted to the ICU, of whom 59 (24%) had SA-AKI. In a stratified subanalysis based on ICU admission, AKI was associated with higher all-cause, in-hospital, and cardiovascular mortality (P<0.001) (
Suppl. 9). Among non-ICU patients, AKI remained an independent predictor of all-cause mortality (adjusted HR, 1.43; 95% CI, 1.10–1.87), in-hospital mortality (adjusted HR, 2.02; 95% CI, 1.28–3.17), and cardiovascular death (adjusted HR, 3.01; 95% CI, 1.59–6.18). In contrast, among ICU patients, AKI was not associated with all-cause or in-hospital mortality but remained a significant predictor of cardiovascular death (HR, 3.89; 95% CI, 2.06–7.35) (
Suppl. 10).
DISCUSSION
In this study, we examined whether the established association between AKI and mortality also applies to patients presenting with early-stage sepsis in the ED, including those not admitted to the ICU. Our objective was to determine whether early kidney dysfunction indicates future risk in patients with early-stage sepsis. We hypothesized that the current understanding of SA-AKI is incomplete, as most existing research has focused on critically ill populations, even though many patients are managed outside intensive care. Our findings demonstrate that AKI is associated with increased all-cause mortality, in-hospital mortality, and cardiovascular mortality in ED patients with early sepsis. These associations remained significant after adjustment for age, sex, comorbidities, and sepsis severity, and persisted even among patients managed exclusively outside the ICU. By focusing on the ED population, we captured SA-AKI at the earliest stage of the hospital course, providing an unbiased perspective across the full disease spectrum. This approach offers a more comprehensive understanding of the clinical relevance of SA-AKI in emergency care and underscores the importance of recognizing and addressing it early, as these patients may be underrecognized within current care pathways.
Survival among patients presenting to the ED with early sepsis was significantly reduced in those with SA-AKI, mirroring outcomes previously observed in critically ill populations. The in-hospital mortality rate of 8% among our early sepsis cohort lies at the lower end of the range reported in prior studies [
20]. This likely reflects the inclusion of patients with a wider range of illness severity, without preselection for ICU admission, and the use of Sepsis-2 criteria to identify early sepsis based on parameters measurable at the ED. In our cohort, the overall mortality rate for patients with SA-AKI was 37.8% after a median follow-up of 346 days, consistent with ICU-based studies reporting mortality rates of 20% to 50% [
4,
21]. Similarly, the 20% in-hospital mortality observed among SA-AKI patients aligns with the 20% to 60% range reported for ICU populations [
6,
7,
22]. Notably, even nonsevere SA-AKI (KDIGO grade 1) was independently associated with increased in-hospital mortality [
3,
23]. This finding cannot be attributed solely to loss of renal function [
24]. Prior studies have demonstrated distant organ interactions in SA-AKI, including macrophage infiltration and inflammatory crosstalk [
24,
25]. Consequently, the presence of even mild SA-AKI may indicate broader organ involvement in early sepsis, contributing to a higher in-hospital mortality risk. In our subgroup analysis of patients managed outside the ICU, AKI remained significantly associated with mortality, confirming that the observed associations were not driven by the 25% of SA-AKI patients requiring ICU care. By focusing on SA-AKI from the point of ED presentation, our study uniquely shows that the adverse prognostic implications of AKI extend across all care settings, highlighting the need for earlier recognition and proactive monitoring of all SA-AKI patients.
Our findings further demonstrate that AKI serves as an early warning signal, akin to a “canary in the coal mine,” for long-term adverse outcomes, including cardiovascular mortality, in patients with sepsis across all levels of care. The interrelationship between cardiovascular and renal outcomes is well established [
5,
26], as reflected in our cumulative incidence analyses showing that, following the acute phase, the probability of death from cardiovascular causes continues to rise (
Suppl. 8). The increased long-term mortality risk after AKI likely results from maladaptive repair processes in which persistent inflammation and fibrosis following sepsis-related injury cause enduring vascular and renal damage [
26–
28]. This maladaptive response is exacerbated by prolonged sepsis, recurrent AKI episodes, and advanced age [
28]. Importantly, maladaptive repair can often be identified during hospitalization. Previous studies have shown that survivors of SA-AKI who experience full renal recovery at discharge have similar long-term outcomes in kidney function and mortality as patients without AKI [
29,
30]. Thus, AKI in early sepsis—often presumed in the ED to be prerenal and transient, particularly in patients not requiring intensive care—actually represents a substantial risk factor for long-term and cardiovascular mortality. These patients may benefit from targeted in-hospital management and structured post-discharge follow-up to mitigate these risks.
Surviving sepsis is frequently followed by post-sepsis syndrome [
31,
32], characterized by an increased risk of rehospitalization, long-term organ dysfunction—particularly cardiac and renal—along with elevated mortality and persistent physical, cognitive, and psychological impairments [
31,
33,
34]. Despite growing awareness of these long-term consequences, many sepsis survivors receive inadequate post-discharge care, and evidence-based strategies to mitigate these outcomes remain limited [
35]. In an international survey, nearly 30% of sepsis survivors reported receiving no post-discharge care [
31]. Even when such care is provided, a German study showed that it is often poorly timed, insufficiently tailored, and misaligned with patients’ actual needs [
36]. Nevertheless, multiple studies have demonstrated that structured post-discharge care can improve long-term outcomes among sepsis survivors. A population-based study from Taiwan found a reduction in 10-year mortality among sepsis survivors referred to rehabilitation following ICU discharge [
37]. Similarly, improved 5-year survival rates were reported among patients with severe sepsis, sepsis, and severe infections, including those not meeting Sepsis-3 criteria, highlighting the broader benefits of post-discharge rehabilitation [
38]. Our findings indicate that SA-AKI present at ED admission is associated with long-term risks and should be incorporated into post-sepsis care strategies regardless of clinical trajectory. Although a standardized model for post-sepsis care has yet to be established, our results support actionable interventions such as in-hospital monitoring of kidney function recovery and structured outpatient follow-up that addresses both renal and cardiovascular health.
This study has several limitations. Its single-center design may limit external generalizability; however, the hospital serves a large geographical catchment area that includes both rural and urban populations, ensuring a diverse patient base encompassing academic and nonacademic care. Urine output was not included in AKI classification due to its limited availability in the ED setting. Subgroup analyses indicated potential overfitting because of small event numbers and covariate adjustments, though the main conclusions remained consistent across crude and stepwise models (
Suppl. 5,
6).
Future research should aim to develop patient-centered care models addressing the full continuum of sepsis survivorship, regardless of initial care setting, to enable sepsis-specific aftercare programs tailored to individual needs. Prospective studies, including randomized controlled trials, are necessary to determine whether specialized aftercare improves outcomes such as long-term mortality, functional recovery, and quality of life. Establishing dedicated outpatient clinics for structured follow-up could play a pivotal role in implementing these programs, improving patient education, and generating real-world data to evaluate their effectiveness.
Conclusions
SA-AKI identified at ED presentation is independently associated with increased all-cause mortality, in-hospital mortality, and cardiovascular mortality. Notably, these associations persist even among patients who do not require ICU care. This underscores the importance of recognizing SA-AKI across all clinical care settings and highlights the need for greater awareness of its prognostic significance. Patients presenting with SA-AKI may benefit from structured follow-up, including ongoing monitoring for cardiovascular and renal complications, and tailored post-discharge care aimed at improving long-term outcomes.
NOTES
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Author contributions
Conceptualization: TJvdA, MvL, HRB, SJLB; Data curation: TJvdA, RJvW, HRB, JCtM; Formal analysis: TJvdA, MvL, HRB; Investigation: TJvdA, MvL, HRB; Methodology: TJvdA, MvL, HRB, JCtM, SJLB; Project administration: MvL, HRB; Resources: MvL, HRB, JCtM; Software: RJvW; Supervision: MvL, HRB, JCtM, SJLB; Validation: MvL; Visualization: TJvdA; Writing–original draft: TJvdA; Writing–review & editing: all authors. All authors read and approved the final manuscript.
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Conflicts of interest
Tamar J. van der Aart is supported by an MD/PhD grant from the University of Groningen, University Medical Center Groningen. The authors have no other conflicts of interest to declare.
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Funding
The authors received no financial support for this study.
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Acknowledgments
The authors express their gratitude to the Acutelines research group for bedside patient inclusion at the University Medical Center Groningen. The authors thank the Acutelines mortality adjudication committees for their contribution to this article, especially A.D. Schoonhoven, I. Koliaki, and E. Aquazadeh. Lastly, the authors express their gratitude to the adjudication committee of Acutelines especially to M. Visser, J. van Everdink, and S. ter Horst.
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Data availability
Data analyzed from this study are not publicly available due to privacy and confidentiality restrictions imposed by European privacy regulations and the Central Ethical Consent Commission of the University Medical Center Groningen. The dataset includes identifiable information, such as hospitalization dates, date of death, and cause of death. However, reasonable requests for data or specific inquiries may be directed to the corresponding author, who will provide information consistent with institutional and ethical standards.
SUPPLEMENTARY MATERIAL
Fig. 1.Kaplan-Meier curve analyses for main mortality outcomes. (A) All-cause mortality. (B) In-hospital mortality. (C) Cardiovascular death. SA-AKI, sepsis-associated acute kidney injury.
Fig. 2.Kaplan-Meier curve analyses by sepsis-associated acute kidney injury (SA-AKI) severity according to KDIGO (Kidney Disease: Improving Global Outcomes) grade. (A) All-cause mortality. (B) In-hospital mortality.
Table 1.
Table 1.
|
Characteristic |
Total (n=2,045) |
SA-AKI (n=246) |
Sepsis without SA-AKI (n=1,799) |
P-value |
|
Age (yr) |
67 (55–75) |
68 (58–75) |
67 (55–75) |
0.24 |
|
Male sex |
1,175 (57.5) |
154 (62.6) |
1,021 (56.8) |
0.09 |
|
Body mass index (kg/m2) |
26.8±6.3 |
27.5±6.5 |
26.7±6.2 |
0.07 |
|
Comorbidity |
|
|
|
|
|
CCI score |
|
|
|
|
|
0–2 |
588 (28.8) |
60 (24.4) |
528 (29.4) |
0.11 |
|
2–4 |
594 (29.0) |
69 (28.0) |
525 (29.2) |
0.71 |
|
4–6 |
488 (23.9) |
59 (24.0) |
429 (23.8) |
0.96 |
|
>6 |
375 (18.3) |
58 (23.6) |
317 (17.6) |
0.02 |
|
Diabetes |
447 (21.9) |
77 (31.3) |
370 (20.6) |
<0.001 |
|
Cardiovascular disease |
582 (28.5) |
83 (33.7) |
499 (27.7) |
0.06 |
|
Malignancy |
626 (30.6) |
71 (28.9) |
555 (30.8) |
0.56 |
|
History of transplanted organ |
245 (12.0) |
48 (19.5) |
197 (11.0) |
<0.001 |
|
Preexisting renal disease |
369 (18.0) |
77 (31.3) |
292 (16.2) |
<0.001 |
|
Baseline creatinine (µmol/L) |
85 (69–115) |
98 (72–157) |
84 (68–111) |
<0.001 |
|
Clinical presentation |
|
|
|
|
|
NEWS2 score |
4 (2–6) |
5 (2–8) |
4 (2–6) |
<0.001 |
|
SOFA score |
2 (1–3) |
4 (2–7) |
2 (0–3) |
<0.001 |
|
Sepsis-3 (qSOFA ≥2) |
205 (10.0) |
55 (22.4) |
150 (8.3) |
<0.001 |
|
Heart rate (/min) |
99±21 |
101±21 |
99±23 |
0.39 |
|
Systolic blood pressure (mmHg) |
129±24 |
120±29 |
130±23 |
<0.001 |
|
Respiratory rate (breaths/min) |
22±6 |
22±6 |
22±6 |
0.15 |
|
Temperature (°C) |
37.4±1.1 |
37.2±1.4 |
37.4±1.1 |
0.01 |
|
Saturation |
96 (94–98) |
96 (94–98) |
96 (94–98) |
0.69 |
|
O2 supplementation |
628 (30.7) |
75 (30.5) |
553 (30.7) |
0.88 |
|
Symptoms of respiratory failure |
760 (37.2) |
94 (38.2) |
666 (37) |
0.73 |
|
GCS score (<14) |
107 (5.2) |
25 (10.2) |
82 (4.6) |
<0.001 |
|
Laboratory parameter |
|
|
|
|
|
Hemoglobin (mmol/L) |
7.2±1.5 |
6.7±1.7 |
7.4±1.5 |
<0.001 |
|
Leukocytes (×109/L) |
9.6 (6.8–14.8) |
10.6 (7.3–18.3) |
9.4 (6.7–14.6) |
0.01 |
|
Platelets (×109/L) |
214 (155–282) |
204 (135–272) |
216 (157–284) |
0.04 |
|
C-reactive protein (mg/L) |
80 (39–181) |
157 (59–276) |
76 (38–166) |
<0.001 |
|
Lactate (mmol/L) |
1.2 (0.8–1.7) |
1.3 (0.8–2.0) |
1.1 (0.8–1.6) |
0.02 |
|
Creatinine (µmol/L) |
89 (68–132) |
194 (135–348) |
84 (65–114) |
<0.001 |
|
AKI severity |
|
|
|
- |
|
AKI KDIGO grade 1 |
154 (7.5) |
154 (62.6) |
0 (0) |
|
|
AKI KDIGO grade 2 or 3 |
92 (4.5) |
92 (37.4) |
0 (0) |
|
Table 2.Summary of patient outcomes
Table 2.
|
Outcome |
Total (n=2,045) |
SA-AKI (n=246) |
Sepsis without SA-AKI (n=1,799) |
P-value |
|
Hospital outcome |
|
|
|
|
|
Length of hospital stay (day) |
6 (4–11) |
9 (5–16) |
6 (4–10) |
<0.001 |
|
ICU admission |
196 (9.6) |
59 (24.0) |
137 (7.6) |
<0.001 |
|
Renal replacement therapy |
14 (0.7) |
9 (3.7) |
5 (0.3) |
<0.001 |
|
Death |
|
|
|
|
|
In-hospital death |
167 (8.2) |
50 (20.3) |
117 (6.5) |
<0.001 |
|
All-cause mortality |
505 (24.7) |
93 (37.8) |
412 (22.9) |
<0.001 |
|
Follow-up time (day) |
346 (155–581) |
261 (36–513) |
363 (166–589) |
<0.001 |
|
Cause of death |
|
|
|
|
|
CV |
63/505 (12.5) |
18/93 (19.4) |
45/412 (10.9) |
0.03 |
|
Infection |
156/505 (30.9) |
35/93 (37.6) |
121/412 (29.4) |
0.12 |
|
Respiratory |
24/505 (4.8) |
5/93 (5.4) |
19/412 (4.6) |
0.75 |
|
Malignancy |
175/505 (34.7) |
18/93 (19.4) |
156/412 (37.9) |
<0.001 |
|
Other |
39/505 (7.7) |
9/93 (9.7) |
30/412 (7.3) |
0.43 |
|
Unknown |
48/505 (9.5) |
8/93 (8.6) |
41/412 (10.0) |
0.69 |
|
Non-CV cause of deatha)
|
394/505 (78.0) |
67/93 (72.0) |
326/412 (79.1) |
0.19 |
Table 3.Association between SA-AKI and mortality
Table 3.
|
Variable |
All-cause mortality |
In-hospital mortality |
Cardiovascular death |
|
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
|
Crude model |
1.94 (1.55–2.43) |
<0.001 |
1.89 (1.36–2.65) |
<0.05 |
3.21 (1.84–5.61) |
<0.05 |
|
Adjusted modela)
|
1.44 (1.14–1.82) |
0.003 |
1.65 (1.16–2.34) |
<0.05 |
2.50 (1.39–4.48) |
<0.05 |
Table 4.Association between SA-AKI KDIGO grades and mortality
Table 4.
|
AKI KDIGO grade |
No. of patients |
All-cause mortality |
In-hospital mortality |
Cardiovascular death |
|
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
|
Crude model |
|
|
|
|
|
|
|
|
Grade 1 |
154 |
1.75 (1.32–2.32) |
<0.05 |
1.82 (1.20–2.74) |
<0.05 |
2.36 (1.11–5.00) |
<0.05 |
|
Grades 2–3 |
92 |
2.27 (1.63–3.15) |
<0.05 |
2.00 (1.26–3.16) |
<0.05 |
4.72 (2.31–9.67) |
<0.05 |
|
Adjusted modela)
|
|
|
|
|
|
|
|
|
Grade 1 |
154 |
1.20 (0.89–1.63) |
0.23 |
1.69 (1.10–2.58) |
0.02 |
1.81 (0.83–3.93) |
0.13 |
|
Grades 2–3 |
92 |
1.96 (1.40–2.74) |
<0.001 |
1.59 (0.98–2.60) |
0.06 |
3.77 (1.79–7.96) |
<0.001 |
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, Jan C. ter Maaten1,2
