Background
Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU), but incidence rates depend upon the burn population studied and AKI definition used [
1,
2]. Consensus definitions of AKI are developed to include all severities of AKI and allow comparison between studies; these are the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) [
3]; Acute Kidney Injury Network (AKIN) [
4]; and Kidney Disease: Improving Global Outcomes (KDIGO) criteria [
5].
Several risk factors for AKI are identified in burn patients such as high age, burn injury extent and/or mechanism, and presence of multiple organ failure and/or sepsis [
2]. However, the results of prophylactic strategies have so far mostly been disappointing [
6]. AKI is a heterogeneous condition ranging from subclinical decline in kidney function to need of renal replacement therapy (RRT). Despite development of international treatment guidelines [
5], the practical handling of AKI, and use of RRT, varies substantially across the world [
7].
AKI in burn patients is associated with increased mortality [
2,
8] and probably also increased length of stay (LOS) [
2]. From other patient groups, it has become evident that survivors of AKI are prone to developing chronic kidney disease (CKD) and have increased long-term morbidity and mortality [
9]. AKI may also be a burden to the health care system, leading to substantially increased treatment costs, especially related to use of RRT [
10].
The purpose of the present study was to review incidence, risk factors, and outcomes of AKI in burn patients admitted to the ICU. Secondary aims were to review the use of renal replacement therapy (RRT) and impact on health care costs.
Discussion
This systematic review reveals that AKI occurs in approximately 38% of burn patients admitted to the ICU, with use of RRT in 12% of all patients. Burn patients at risk for AKI have high age, chronic hypertension, diabetes mellitus, high TBSA percent burnt, high ABSI score, inhalation injury, rhabdomyolysis, surgery, high APACHE II score, high SOFA score, sepsis, and mechanical ventilation. Development of AKI after burn is associated with prolonged stay in ICU and hospital, and reduced chance of survival. Kidney function seems to recover well in most burn patients with AKI. Notably, no study reported the economic consequences of AKI after burns.
A previous study of mixed ICU patients observed that 57% of the patients experienced AKI according to the KDIGO criteria, and 13.5% underwent RRT [
59]. In a meta-analysis of burn patients assessed by the RIFLE criteria, AKI was present in 30–66% of the patients, and RRT used in 5% [
8]. In comparison, this systematic review using several criteria revealed 38% with AKI and 12% treated with RRT. The incidence of AKI and use of RRT varied widely among the included studies; this may partly be explained by large differences in burn populations. It is likely, however, that many of the studies in this systematic review underreported the incidence of AKI due to the use of modified AKI criteria.
High age, chronic hypertension, and diabetes mellitus are known risk factors for AKI [
12,
59]. An earlier meta-analysis found that inhalation injury, high TBSA percent burnt, and high ABSI score were risk factors for AKI after burn [
2]. Our data suggest that rhabdomyolysis and surgery are additional burn-related risk factors. AKI is often present in the most severely ill patients as indicated by high APACHE II and SOFA scores [
2,
12]. Sepsis and use of mechanical ventilation have also previously been associated with increased risk of AKI in critically ill patients [
2,
60,
61].
AKI in ICU patients is often part of multiple organ failure [
1,
62,
63]. In line with this, we observed that patients with AKI had more than one week longer ICU and hospital LOS compared to non-AKI patients. A similar observation was recently observed in a meta-analysis of major trauma patients [
12]. The effect on LOS in our systematic review may be underestimated, since patients with AKI might have a high early mortality not adjusted for in many of the included studies.
In the present study, AKI after burns was associated with several-fold increased mortality that was worsened with the severity of AKI disease. A previous systematic review of burn patients with AKI according to the RIFLE criteria reported a mortality rate of 35% [
8]. When applying several AKI criteria, we found that 43% of burn patients with AKI died, and 74% of patients undergoing RRT. In comparison, mortality was 27% in a study of general ICU patients with AKI [
59].
Evaluation of renal recovery is challenging because the definition may vary from full recovery of functional reserve to RRT independence [
64]. In our systematic review, only two studies with consecutive sampling of patients reported renal recovery; these reported that all patients except two had normal kidney function at discharge. This finding should be interpreted with caution due to limited number of patients and insufficient follow-up time to evaluate long-term effects. Previous research suggests that ICU patients with AKI have increased risk of CKD and all-cause mortality compared to patients without AKI [
9].
None of the studies reported the economic consequences of AKI after burns. Despite this, one would assume that both prolonged LOS and use of RRT would increase treatment costs [
65].
This systematic review has a number of clinical limitations. The included studies had large clinical heterogeneity because the study participations and outcome variables varied widely. AKI incidence may be underestimated since many studies used modified AKI criteria. Creatinine levels and urine output are influenced by fluid and/or diuretic therapy not reported in most of the studies. Data on hospital and ICU outcomes are influenced by the local policy for transfer of patients, withholding or withdrawing therapy. The handling of AKI, and particularly the use of RRT, probably varied across sites [
66]. Finally, the applicability of the results on renal recovery may be impaired by variable case definitions and short follow-up times.
Methodological limitations are that some publications may have been missed due to language limitation of the literature search. Complete datasets could not be obtained from five studies. Many of our meta-analyses are characterised by substantial statistical heterogeneity, and hence, many summary estimates are uncertain with wide confidence intervals. This heterogeneity is probably caused by heterogeneity in study populations and study design. We have carried out a large number of subgroup analyses aiming to explore what causes the heterogeneity, but it was impossible to single out factors of particular importance. It seems likely that many factors play a role and that the uncertainty would be reduced if we were able to control for confounding variables and present adjusted summary estimates. Unfortunately, this was not possible without access to individual patient data. We did not formally evaluate potential bias that may be caused by use of means and SDs for skewed variables in our analyses of risk factors. Finally, we were unable to include data on economic costs because of missing data.
Strengths of this systematic review are the high number of included studies and patients. Further, the literature search, study selection, and data extraction were determined and published before study start. Two independent collaborators in duplicate screened studies for eligibility, evaluated quality, and extracted data according to pre-set criteria. Finally, we contacted authors twice by e-mail in order to retrieve complete data from eligible publications.
An implication of this systematic review for clinical practice is that health care personnel should be aware of burn patients at risk for AKI, for instance elderly patients with chronic hypertension, diabetes mellitus, and extensive burn injuries. Future studies should explore long-term patient outcomes and treatment costs of AKI among burn victims. There is a clear need for development of uniform standards of reporting in AKI, especially a consensus definition of renal recovery [
64,
67].
Conclusions
The present systematic review reveals that AKI and use of RRT is common in ICU patients with burn injuries. Patients with high age, chronic hypertension, diabetes mellitus, high TBSA percent burnt, high ABSI score, inhalation injury, rhabdomyolysis, surgery, high APACHE II score, high SOFA score, sepsis, and need for mechanical ventilation are at risk for post-burn AKI. Development of AKI after burn has a negative impact on short-time morbidity and mortality, but we lack data on long-term patient outcomes and economic consequences. Limited data suggests that most survivors of AKI regain their kidney function.
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