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[Intensive Care Monitor]: 危重病患儿及青年人的急性肾损伤流行病学
2017年03月08日 研究点评, 进展交流 暂无评论

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EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN CRITICALLY ILL CHILDREN AND YOUNG ADULTS.

Authors: Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL for the AWARE Investigators.

Reference: N Engl J Med, 2017; 376: 11-20

© Massachusetts Medical Society.

Level of evidence: 4

ICM ABSTRACT

Objective

To define the incremental risk of death and complications associated with severe acute kidney injury (AKI) in critically ill children and young adults.

Introduction

In adult patients, AKI is associated with increases in mortality, mechanical ventilation, and length of stay in the ICU. Outcomes data from small studies are supported by findings from a large, multinational, prospective study that used the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines to describe the epidemiology of adult AKI. By contrast, information about AKI in children is limited. The trial reported here is the Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) study that investigated outcomes in critically ill children and young adults.

Study design

Multinational, prospective, observational study.

Patients and methods

Screening for AKI was carried out during three consecutive months in 2014 and included all patients aged 3 months to 25 years entering 32 pediatric ICUs (PICUs) across Asia, Australia, Europe, and North America. KDIGO criteria were used to define AKI and the presence and severity of AKI was determined for the first 7 days in the ICU; severe AKI was defined as stage 2 or 3. The primary outcome was 28-day mortality. Secondary outcomes were: ICU length of stay and requirement for mechanical ventilation, extracorporeal membrane oxygenation or renal replacement therapy (RRT).

Results

There were 4683 patients with known status for both AKI and 28-day outcome. During the first 7 days after ICU admission, AKI developed in 1261 patients (26.9%; 95% CI: 25.6 to 28.2) and severe AKI developed in 543 (11.6%; 95% CI: 10.7 to 12.5). The maximum stage of AKI reached in this period was stage 1 in 718 patients (15.3%), stage 2 in 294 patients (6.3%), and stage 3 in 249 patients (5.3%). The daily prevalence of AKI increased from 14.5% to 20.4% over the 7 days. Those with stage 1 AKI on Day 1 were more likely to progress to stage 2 or 3 by Day 7 than patients without AKI on Day 1 (14.1% vs. 2.9%, p<0.001). Severe AKI was associated with an increased risk of death (OR: 1.77; 95% CI: 1.17 to 2.68). Death occurred in 60/543 patients (11.0%) with severe AKI as compared with 105/4140 patients (2.5%) without severe AKI (p<0.001). The risk of death associated with stage 3 AKI exceeded the risk associated with no AKI or stage 1 or 2 (p<0.001 all comparisons). When stage 3 AKI was defined by urine output rather than plasma creatinine level higher mortality rates were recorded. In 355 of the 528 patients who met the urine-output criteria for AKI, the diagnosis of AKI would have been missed if only the plasma creatinine criteria had been used. Mortality was higher among patients with low urine output than among those with normal urine output (7.8% vs. 2.9%, p=0.02). Increases in the severity of AKI were associated with increased use of mechanical ventilation, renal-replacement therapy and extracorporeal membrane oxygenation and longer duration of stay in the ICU. Use of renal-replacement therapy was a strong predictor of death by Day 28 (OR: 3.38; 95% CI: 1.74 to 6.54).

Discussion

This large, prospective, multinational study showed that AKI is common and associated with poor outcomes in critically ill children and young adults. It reinforces the need for systematic surveillance for AKI at the time of admission to the ICU and highlights the importance of using both plasma creatinine levels and urine output to define AKI.

ICM COMMENT 1

The AWARE Study is an important epidemiologic study of AKI in critically ill children and young adults (up to age 25). This large, multinational prospective study included 32 PICUs across 4 continents. It is a well done study looking at the prevalence of AKI over the first 7 days in the ICU. AKI occurred in over a quarter of the patients (1261 of 4683 patients, 26.9%) as defined by KDIGO guidelines according to plasma creatinine level and urine output. AKI was severe in 43% of those with AKI. Data were collected on creatinine and urine output; the mortality was higher when AKI was defined by urine output criteria than by creatinine, confirming what those of us who care for critically ill children know – oliguria is bad. AKI was defined by urine output criteria in 528 patients; of those, 355 had normal creatinine levels and the diagnosis of AKI would have been missed.

The authors report that the daily prevalence of AKI increased with each additional day in the PICU. AKI was associated with increased mortality, mechanical ventilation, RRT and PICU length of stay. Increasing severity of AKI was associated with increasing risk of mortality as well as increased length of stay.

Data on baseline creatinine levels up to 3 months prior to admission were also included. Nearly half had a baseline creatinine reported; the creatinine was assumed to be normal if it was not available. Interestingly, the 2533 patients without a reported baseline creatinine had shorter PICU lengths of stay and less RRT and mechanical ventilation that the 2451 patients with a reported baseline creatinine.

Previous studies of AKI in children have used different definitions. This study uses a standardized classification for AKI and is a valuable contribution to our care of critically ill children. The 26.9% rate of AKI in this study should give us pause and encourage us to look for ways to prevent AKI, including avoiding nephrotoxins and attending closely to fluid and electrolyte management. This study also brings home the importance of paying attention to the urine output, as reliance on the creatinine alone may lead us to miss many children with AKI. As we are making efforts to avoid urinary tract infections by limiting the use of bladder catheters, we will have to be even more diligent in our attention to urine output. The authors did not collect data on diuretic use, so we cannot determine from this study whether such therapies might avoid AKI, reduce its severity, or improve outcomes. Nonetheless, it is a valuable contribution to the literature.

The bottom line is that AKI is common in critically ill children and is associated with increased mortality and resource utilization. Urine output is an important factor to assess to identify children with AKI, as AKI may occur with normal creatinine. MMP.

 

ICM COMMENT 2

In the last decade, there has been a profound transformation in the field of AKI due to 4 important advancements: the recognition that even relatively small increments in serum creatinine are associated with mortality, the development and refinement of standardized definitions of AKI, the discovery of new biomarkers of AKI and the understanding that AKI is associated with serious short and long-term complications.

Most data stem from adults and less was known about paediatric AKI. It is on this background that the AWARE study was conducted. [1] It is the largest prospective international multicentre study to determine the incidence and outcome of AKI in critically ill children aged 3 months to 25 years. The key findings were that AKI was common and independently associated with an increased risk of 28-day mortality and need for mechanical ventilation and RRT after adjustment for 16 covariates. Although this observation mirrors results seen in adults [2], the low prevalence of chronic comorbid diseases in children means that AKI per se may be the key to the associated morbidity and mortality.

A second important finding is the confirmation that urine output criteria should not be ignored when determining the epidemiology of AKI. AKI stage 3 based on urine output values conferred a higher mortality risk than AKI stage 3 defined by serum creatinine results. [1] Importantly, in 67% of the patients who met the urine output criteria, the diagnosis of AKI would have been missed if only the serum creatinine criteria had been applied. This is relevant since many previous reports on the prevalence of AKI in adults and children are based on the serum creatinine criteria alone. [3, 4] The results by Kaddoura et al again mirror the findings of a large study conducted in adults. [5] Kellum and colleagues analysed >32,000 critically ill adult patients and showed that short- and long-term risk of death or RRT were greatest when patients met creatinine and urine criteria for AKI. Both studies emphasize the strong role of oliguria as a marker of renal function independent of age group.

Despite the impressive results, some important questions remain. The age span of participants was substantial (3 months to 25 years). Given that there are obvious differences between young infants, children, adolescents and young adults, it is unclear whether there are also differences in outcome between these age groups when affected by AKI and whether any groups are particularly at risk. Another question is whether children who survive an episode of AKI have similar long-term complications as adults, including chronic kidney disease, end stage renal failure, cardiovascular events and an increased risk of fractures. [2] Kaddourah and colleagues only reported follow-up data until day 28 but hopefully their large database will provide enough opportunities for further long-term and subgroup analyses.

In conclusion, Kaddourah and colleagues closed the gap between adult and paediatric critical care nephrology and confirmed that AKI is a serious condition independent of age and comorbidities.

The bottom line is that AKI is common among children and young adults admitted to PICUs and independently associated with increased mortality. MO.

References:

1. Kaddourah A et al. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 2017;376(1):11-20

2. Chawla LS et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371: 58-66

3. Selewski DT et al. Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med 2014;40:1481-1488

4. Sutherland SM et al. AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol 2015;10: 554-561

5. Kellum JA et al. Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 2015;26(9):2231–2238

 

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