Early reversible acute kidney injury is associated with improved survival in septic shock

doi:10.1016/j.jcrc.2014.04.003

Journal of Critical Care

Volume 29, Issue 5, October 2014, Pages 711-717

https://doi.org/10.1016/j.jcrc.2014.04.003 Get rights and content

Abstract

Introduction

The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤ 24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock.

Methods

Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality.

Results

During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI.

Conclusion

In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system.

Introduction

Acute kidney injury (AKI) is associated with adverse outcomes, universally increasing mortality, length of hospital stay and the risk of long term chronic kidney disease and kidney failure [1], [2], [3], [4], [5], [6], [7], [8], [9], [10]. In septic shock, AKI is especially common with the risk of worse outcomes increasing with the severity of injury [2], [4], [11], [12], [13], [14], [15], [16].

Current classification schemes for defining AKI, such as the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) system and the Acute Kidney Injury Network (AKIN) system define the stage and severity of AKI using criteria based on declining urine output and changes in serum creatinine compared to baseline [17], [18], [19], [20], [21]. AKI is then classified according to the most severe stage achieved at any time point, regardless of reversibility. Although this classification has been validated in large international AKI datasets, little is known regarding the impact of earl (≤ 24 hours) reversibility of AKI on outcomes [17], [18], [19]. In this retrospective analysis, we examined the effect of early reversibility of AKI on in-hospital mortality in septic shock.

Section snippets

Study population

The Cooperative Antimicrobial Therapy of Septic Shock (CATSS) database is an international, multicenter database of patients admitted with septic shock to an intensive care unit (ICU). The CATSS database, which has been described in detail previously, uses standardized case definitions and includes repeat serum creatinine measurements during the first 24 hours of admission [13], [22], [23]. The database captures information on consecutive adult (> 18 years old) patients admitted with septic

Results

During the study period, 709 (13.0%) exhibited reversible AKI, 2878 (54.9%) persistent AKI, 635 (11.7%) new AKI and 1221 (22.4%) no AKI. Improved AKI occurred in 1041 (19.1%) individuals. ICU and in-hospital morality occurred in 1851 (34.0%) and 2477 (45.5%), respectively. In hospital mortality occurred in 150 (21.2%) with reversible AKI, 1524 (53.0%) with persistent AKI, 389 (61.3%) with new AKI and 414 (33.9%) with no AKI. Table 1 outlines the study characteristics stratified by AKI status.

Discussion

In this large, international, observational cohort study of patients with septic shock admitted to the ICU, reversibility of AKI was associated with a decreased risk of mortality. Even without complete reversal of AKI, a survival benefit was noted with any improvement in AKI severity. Furthermore independent of AKI classification, individuals with the largest decline in creatinine with the first 24 hours of ICU admission demonstrated a similar survival benefit. These findings suggest that

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We searched three databases (PubMed, Web of Science, and Cochrane) for randomised controlled trials and cohort studies published up to March 28, 2022, and manually searched for relevant references. We included data from adults older than 18 years of age with sepsis-associated AKI. The Newcastle–Ottawa Scale and the Cochrane Risk of Bias tool were used for quality assessment. The primary outcome was 28-day mortality. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were used for meta-analysis.
There were a total of 3648 patients from four randomised controlled trials and eight cohort studies. The pooled results indicated that compared to delayed RRT, early RRT had a lower 28-day mortality (RR: 0.72; 95% CI: 0.59–0.88; P = 0.001; I² = 76%), and this result was robust according to sensitivity analysis, and no significant difference in 90-day mortality (RR: 0.80; 95% CI: 0.64–1.00; P = 0.05; I² = 82%),180-day mortality (RR: 1.07; 95% CI: 0.93–1.23; P = 0.36; I² = 0%), length of intensive care unit stay (MD − 0.94; 95% CI −2.43–0.55; P = 0.22; I² = 0%), length of hospital stay (MD − 1.02; 95% CI −4.21–2.17; P = 0.53; I² = 0%), and RRT dependence was found among survivors at 28 days (RR: 1.21; 95% CI: 0.73–2.00; P = 0.47; I² = 0%). Subgroup analysis of 28-day mortality showed that patients with sepsis-associated AKI who received early RRT at Kidney Disease: Improving Global Outcomes stage 2 or Sequential Organ Failure Assessment score ≤12 had a better chance of survival.
Early RRT may be beneficial to the 28-day short-term survival rate of patients with sepsis-associated AKI in Kidney Disease: Improving Global Outcomes stage 2 and having Sequential Organ Failure Assessment score less than or equal to 12 but has no significant effect on long-term survival, length of intensive care unit stay, the total length of hospital stay, and 28-day RRT dependence of survivors. These results still need to be confirmed by more large-scale randomised controlled studies.
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Overall AKI occurred in 59.2% in which two thirds developed stage 2–3 AKI. Recovery rate of AKI at hospital discharge was 80.8%. Patients who did not recover experienced the worst 15-year mortality compared to those who recovered and those without AKI (57.8% vs 45.2% vs 30.3%, p < 0.001). This pattern was also found in subgroups of patients with suspected sepsis-associated (57.1% vs 47.9% vs 36.5%, p < 0.001) and cardiac surgery-associated AKI (60.1% vs 41.8% vs 25.9%, p < 0.001). The rates of dialysis and transplantation at 15 years were low and not associated with recovery status.
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In experimental sepsis, functional and morphological effects of bone marrow-derived mononuclear cell (BMDMC) administration in lung tissue have been evaluated 1 and 7 days after therapy. However, to date no study has evaluated the early effects of BMDMCs in both lung and kidney in experimental polymicrobial sepsis.
Twenty-five female C57BL/6 mice were randomly divided into the following groups: 1) cecal ligation and puncture (CLP)-induced sepsis; and 2) Sham (surgical procedure without CLP). After 1 h, CLP animals received saline (NaCl 0.9%) (CLP-Saline) or 10⁶ BMDMCs (CLP-Cell) via the jugular vein. At 6, 12, and 24 h after saline or BMDMC administration, lungs and kidneys were removed for histology and molecular biology analysis.
In lungs, CLP-Saline, compared to Sham, was associated with increased lung injury score (LIS) and keratinocyte chemoattractant (KC) mRNA expression at 6, 12, and 24 h. BMDMCs were associated with reduced LIS and KC mRNA expression regardless of the time point of analysis. Interleukin (IL)− 10 mRNA content was higher in CLP-Cell than CLP-Saline at 6 and 24 h. In kidney tissue, CLP-Saline, compared to Sham, was associated with tubular cell injury and increased neutrophil gelatinase-associated lipocalin (NGAL) levels, which were reduced after BMDMC therapy at all time points. Surface high-mobility-group-box (HMGB)− 1 levels were higher in CLP-Saline than Sham at 6, 12, and 24 h, whereas nuclear HMGB-1 levels were increased only at 24 h. BMDMCs were associated with decreased surface HMGB-1 and increased nuclear HMGB-1 levels. Kidney injury molecule (KIM)− 1 and IL-18 gene expressions were reduced in CLP-Cell compared to CLP-Saline at 12 and 24 h.
In the present experimental polymicrobial sepsis, early intravenous therapy with BMDMCs was able to reduce lung and kidney damage in a time-dependent manner. BMDMCs thus represent a potential therapy in well-known scenarios of sepsis induction.
To evaluate early bone marrow-derived mononuclear cell (BMDMC) therapy on lung and kidney in experimental polymicrobial sepsis.
Twenty-five female C57BL/6 mice were randomly divided into the following groups: cecal ligation and puncture (CLP)-induced sepsis; and sham (surgical procedure without CLP). After 1 h, CLP animals received saline (CLP-saline) or 10⁶ BMDMCs (CLP-cell) via the jugular vein. Lungs and kidneys were evaluated for histology and molecular biology after 6, 12, and 24 h.
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Sepsis remains the most common cause of acute kidney injury (AKI) and is associated with a high mortality. This study aims to identify laboratory, clinical and demographic factors that are associated with the different stages of AKI in sepsis.
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We conducted a retrospective single-center analysis of 192 hospitalized COVID-19 patients from March to May of 2020. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (SCr) criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions.
In this cohort of COVID-19 patients, 55.2% developed AKI (n = 106). The majority of AKI patients had persistent AKI (n = 64, 60.4%). Overall, in-hospital mortality was 18.2% (n = 35) and was higher in AKI patients (28.3% vs. 5.9%, p < 0.001, unadjusted OR 6.03 (2.22–16.37), p < 0.001). In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02–1.11), p = 0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60–0.98), p = 0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37–22.72), p = 0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32–5.33), p = 0.006) were independent predictors of mortality.
AKI was frequent in hospitalized patients with COVID-19. Persistent AKI and higher severity of AKI were independent predictors of in-hospital mortality.
La incidencia de lesión renal aguda (LRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19) oscila entre el 0,5 y el 35% y se ha asociado a peor pronóstico. El propósito de este estudio fue evaluar la incidencia, gravedad, duración, factores de riesgo y pronóstico de la LRA en pacientes hospitalizados con COVID-19.
Realizamos un análisis retrospectivo de un solo centro de 192 pacientes con COVID-19 hospitalizados de marzo a mayo de 2020. La LRA se diagnosticó utilizando la clasificación Kidney Disease Improving Global Outcome (KDIGO) basada en criterios de creatinina sérica (SCr). La LRA persistente y la transitoria se definieron de acuerdo con las definiciones del grupo de trabajo de la Iniciativa de Calidad de Enfermedades Agudas (ADQI).
En esta cohorte de pacientes con COVID-19, el 55,2% desarrolló LRA (n = 106). La mayoría de los pacientes tenían LRA persistente (n = 64; 60,4%). En general, la mortalidad hospitalaria fue del 18,2% (n = 35) y fue mayor en los pacientes con LRA (28,3% frente a 5,9%; p < 0,001), (OR no ajustada 6,03; IC 95%: 2,22-16,37; p < 0,001). En este análisis multivariado, mayor edad (OR ajustada 1,07; IC 95%: 1,02-1,11; p = 0,004), menor nivel de Hb (OR ajustada 0,78; IC 95%: 0,60-0,98; p = 0,035), duración de la LRA (OR ajustada 7,34 para LRA persistente; IC 95%: 2,37-22,72; p = 0,001) y la gravedad de LRA (OR ajustada 2,65 por aumento en el estadio KDIGO; IC 95%: 1,32-5,33; p = 0,006) fueron predictores independientes de mortalidad.
La LRA fue frecuente en pacientes hospitalizados con COVID-19. La LRA persistente y su mayor gravedad fueron predictores independientes de mortalidad hospitalaria.

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^☆: All authors approved of this manuscript.

^☆☆

Conflict of Interest Statement: Anand Kumar received unrestricted grant funding from Pfizer, Lilly, Astellas, Bayer, and Merck for the initial development of the CATSS Database. Additional grant funding has been provided by the Manitoba Research Council, the Health Sciences Foundation and the Deacon Foundation. No other author has significant conflict of interest. This specific analysis has not been supported.

Manish Sood has salary support through the Jindal Research Chair for the Prevention of Kidney Disease at the University of Ottawa.

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Infection/SepsisEarly reversible acute kidney injury is associated with improved survival in septic shock☆,☆☆

Abstract

Introduction

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Am J Kidney Dis

Am J Kidney Dis

Int J Infect Dis

J Crit Care

Chest

Chest

Kidney Int

Am J Kidney Dis

J Crit Care

Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population based study

Crit Care

Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes

Clin J Am Soc Nephrol

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group

Crit Care

Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome

J Am Soc Nephrol

The effect of acute renal failure on mortality. A cohort analysis

JAMA

Acute renal failure in critically ill patients

JAMA

Acute kidney injury criteria predict outcomes of critically ill patients

Crit Care Med

Chronic dialysis and death among survivors of acute kidney injury requiring dialysis

JAMA

and the ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation

Crit Care

Infection/Sepsis
Early reversible acute kidney injury is associated with improved survival in septic shock☆,☆☆