Importance of duration of acute kidney injury after severe trauma: a cohort study

Background

Acute kidney injury (AKI) occurs in up to half of critically injured patients and is one of the most common manifestations of organ failure after severe trauma.1 2 Post-traumatic AKI is associated with prolonged length of stay, discharge to a destination other than home, and increased mortality.1 3–8 Despite the known consequences of AKI, little progress has been made in the treatment and prevention of AKI after trauma. Interventions that would be expected to have a positive impact on AKI have not demonstrated the predicted effects. For example, damage control resuscitation strategies that have been shown to improve the clinical course of trauma patients have repeatedly failed to show improvement in traditional AKI metrics such as incidence and need for renal replacement therapy.9–11 One reason may be that reporting of AKI incidence has been plagued by changing definitions and lack of standardization of reference creatinine estimates for diagnoses. Another reason may be that there is a spectrum of severity of AKI that is not captured by these traditional metrics. AKI stage and duration are more granular metrics than incidence that may be more useful for testing interventions to improve outcomes.12 Stage of AKI has previously been shown to be associated with poor outcomes after severe trauma.2 However, the prognostic significance of AKI duration has not been evaluated after trauma.

Given the impact of post-traumatic AKI on patient outcomes and resource utilization, quality improvement efforts have focused on AKI prevention including bundles that incorporate judicious fluid management and avoidance of nephrotoxins.13 14 However, the success of these initiatives is predicated on the goal of preventing post-traumatic AKI. Given that many patients arrive with AKI at admission, rapid treatment to shorten the duration and severity of AKI may be a worthy alternative goal of quality improvement efforts.15 It has been previously proposed that physicians should be using AKI duration to measure the effectiveness of an intervention instead of the binary outcome of AKI incidence.16 However, in patients who have suffered severe trauma, the most important metric to capture the burden of AKI remains unknown. In addition to the previously established relationship between AKI incidence and stage with poor outcome, we hypothesized that AKI duration is independently associated with mortality, discharge destination other than home, and prolonged hospitalization.

Methods

A retrospective cohort study was conducted at the Red Duke Trauma Institute at Memorial Hermann Hospital, Texas Medical Center, a high-volume, level 1 trauma center in Houston, Texas, USA. Adult (≥16 years) trauma patients requiring intensive care unit (ICU) admission during a 10-year period from January 2009 to October 2018 were included. Patients with pre-existing end-stage renal disease (ESRD), admitted to the burns service, directly transferred to the ICU, or without a creatinine measurement on arrival were excluded. The primary reasons for missing creatinine was due to primary use of point-of-care creatinine measurement and outside hospital creatinine measurements which were not integrated into the electronic medical records. Demographic characteristics, injury details, and outcomes were obtained from the institution’s prospectively maintained trauma registry. Laboratory results were extracted from the medical record. Discharge destination of home was defined as those who were discharged to a location requiring no advanced care including home, a psychiatric facility, or to jail. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational studies were followed.17

Results

During the study period, 8106 patients were admitted to the ICU after traumatic injury. Patients were excluded for ESRD (n=23), direct to ICU transfer (n=223), primary burn injury (n=25), and no creatinine drawn within 24 hours of arrival (n=786), leaving 7049 patients in the final analysis. After exclusions, less than 1% of data were missing. The median age was 41 (IQR 26–58) years. Male sex was predominant, accounting for 72% of the cohort. Participants were severely injured with a median ISS of 20 (IQR 13–29) (table 1). Patients with AKI, either long or short duration, were older and presented with higher arrival creatinine than patients without AKI. Additionally, they presented with lower hemoglobin and lower base excess values than patients without AKI. Patients with long-duration AKI had similar characteristics as those with short-duration AKI, except patients with long-duration AKI were older.

A total of 3153 (45%) patients suffered AKI during the first 7 days after arrival. Sixty-nine percent of these patients (31% of all patients) had AKI on arrival. The majority of patients with AKI suffered stage 1 (67%). The duration of AKI spanned from 0 to 7 days, with the majority of patients suffering either no AKI days or a short duration of AKI (figure 1). Among patients with AKI, the median duration was 1 day (IQR 1–1). Short-duration AKI was most common in this cohort, with 2303 patients (73%) recovering from AKI within 2 days of onset.

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On multivariable analysis, incidence of AKI was associated with prolonged hospitalization, discharge destination other than home, and mortality (table 2). Incremental increases in AKI stage and AKI duration (per day) were also associated with prolonged hospitalization, discharge destination other than home, and mortality (table 2). Both long (>2 days) and short durations of AKI were positively associated with prolonged hospitalization, discharge destination other than home, and mortality (figure 2). There was a larger and more precise effect of long duration of AKI on poor outcomes than short duration. AKI stage and duration were collinear and were therefore not assessed against each other in one model.

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Discussion

AKI was common during the first week of hospitalization after severe trauma, occurring in almost half of a large population of critically injured patients presenting to a busy urban trauma center. Consistent with prior reports, AKI incidence and stage were associated with prolonged hospitalization, discharge destination other than home, and increased mortality. Additionally, AKI duration was independently and incrementally associated with the same poor outcomes. Due to collinearity, the importance of stage and duration was not directly compared.

Although the relationship between duration and outcomes after trauma has not been previously described, duration of AKI has been noted to be associated with clinical outcomes in other patient populations including medical critical care, cardiac surgery, general hospitalization, and postmyocardial infarction.12 26 Authors have previously distinguished ‘short’ or ‘transient’ duration AKI of ≤2 days from longer durations of AKI. In non-trauma patients, both short-duration and long-duration of AKI have been found to be independently associated with poor long-term outcomes, with a greater magnitude of association with longer duration of AKI. Short-duration AKI was found to be independently associated with mortality, congestive heart failure, and myocardial infarction when compared with patients without AKI.12 27 Long-duration AKI was also associated with increased mortality, myocardial infarction, and development of chronic kidney disease (CKD).12 26 The present study confirms an association between AKI duration and subsequent outcomes in trauma patients.

In non-trauma patients, longer AKI duration was independently associated with poor outcomes after adjusting for stage.12 28 However, in this study of trauma patients, duration and stage were collinear, indicating that duration and stage were not independent. One reason for this difference may be that this study only evaluated relatively short-term outcomes, whereas studies in non-trauma populations measured longer term outcomes such as development of CKD, long-term mortality, or rare events in the generally young and previously healthy population such as congestive heart failure exacerbation and myocardial infarction.12 26 Another reason may be the difference in AKI etiology and time to reversal of the underlying pathophysiology. Over 50% of trauma ICU patients at the study center present with either shock or occult hypoperfusion due to hemorrhage.29 Hemostasis is achieved by a median of 120 minutes from hospital arrival if emergent hemorrhage control is required.30 In contrast, patients with AKI related to sepsis or cardiogenic shock more commonly found in the general ICU literature likely have prolonged renal insults. Finally, the duration that is considered ‘long’ and ‘short’ varies between the trauma literature and the general ICU literature. The impact of long duration on poor outcomes is greatest in patients with an AKI duration of 7 or more days.12 Duration of AKI longer than 7 days was rare in our population, and therefore the distinction between ‘long’ and ‘short’ was made at 2 days (figure 1). A larger multicenter study may determine if AKI in trauma patients is truly different from that in other critically ill patients.

Progress in development of effective therapeutic strategies for the prevention or treatment of AKI has been poor. Supportive care remains the cornerstone of AKI prevention and treatment, regardless of the underlying etiology. According to the KDIGO Clinical Practice Guideline, AKI prevention efforts should include decreasing nephrotoxic exposure, ensuring adequate volume status and perfusion, close monitoring of serum creatinine and urine output, and avoiding hyperglycemia.18 Once AKI has already developed, efforts to mitigate the impact of AKI are limited to avoidance of exacerbating factors and supportive care such as renal replacement therapy. Specific risk factors for post-traumatic AKI include rhabdomyolysis, massive hemorrhage and resuscitation, systemic inflammatory response to trauma, and direct kidney trauma.31 High-quality evidence is lacking regarding the treatment of these underlying conditions to optimize renal recovery.

AKI metrics are used in clinical trials to evaluate the effectiveness of strategies to mitigate or prevent AKI, and to benchmark performance across centers. In trauma, the Trauma Quality Improvement Project (TQIP) provides risk-adjusted outcome metrics to centers for quality improvement purposes. Currently, TQIP only assigns a diagnosis of AKI to those patients who meet criteria for KDIGO AKI stage III. While progression to AKI stage III and need for renal replacement therapy are important outcomes, they only represent a minority of trauma patients with AKI.2 5 6 Thus, interventions to reduce AKI, using this definition, will only potentially benefit a small number of patients. Additionally, this study demonstrated that one-third of severely injured patients admitted to the ICU present with AKI at admission. Thus, incidence of AKI may be just as much a measure of injury severity and prehospital care than trauma center care. Our study suggests that highest stage or duration of AKI would be more granular, clinically relevant metrics to collect than AKI incidence. Additionally, tracking AKI present on arrival would also better inform quality improvement initiatives and clinical trials.

Conclusions

The majority of patients suffered mild severity AKI for a short duration after hospital arrival for severe trauma. Prolonged AKI duration was independently and incrementally associated with worsened outcomes including prolonged hospitalization, discharge destination other than home, and mortality. Additionally, increased AKI stage was associated with poor outcomes. Either or both should be considered additional metrics to incidence in informing quality improvement efforts as well as in benchmarking trauma center quality.