In this retrospective observational study, it was found that firstly, AKI was still a serious issue in severely burned patients with a 38.4% occurrence, and AKI was independently associated with a threefold risk of mortality in severely burned patients. Second, it was obvious that AKI occurred early, with 74% of AKI diagnosed within the first 3 days after severe burn injuries, but late AKI had higher mortality. Third, the AKI predicting model was proved to include age, gender, TBSA, full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burns, inhalation injuries, and myohemoglobin. Tracheotomy and sepsis were independent risk factors for AKI.
AKI is a common complication in severely burned patients. The incidence of AKI in burned patients varied from 1% to 36% depending on the different population studied and diagnostic criteria, and the mortality among burned patients with AKI was 28% to 100% . Other studies have shown that AKI occurred in 53.3% of patients with severe burn injuries, and patients with AKI had a mortality rate of 34.4% . In this study, the incidence of AKI was 36.9% in the patients with burn ≥30% TBSA; the total mortality was 32.3% in the patients with AKI, highest in the patients with late AKI with the mortality up to 56.3%, which was higher in burn patients than in general population . Therefore, it is crucial to early prevent and diagnose AKI in severely burned patients. However, in other study, we found the incidence and mortality of AKI have not decreased in the consecutive six years. Reducing the incidence of AKI and improving the prognosis of patients with AKI are still facing significant difficulties and challenges.
In multinomial logistic regression, the study found that age, gender (male), TBSA, full thickness burns of TBSA, hypertension or/and diabetes, tracheotomy and hypovolemic shock of early burns were independently associated with both early and late AKI development, and sepsis was an independent risk factor for late AKI. However, BMI and drink, smoke, ABSI, etiology of burns and inhalation injuries had no influences, which is similar to previous studies [18-20]. The risk of the aged and male patients suffering early and late AKI increased by over one to five folds, which is in agreement with some studies [21-23], while others found gender is not a predisposing factor for AKI . Considering that more male patients may be engaged in electrical works and suffered electrical injuries which may be a risk factor for AKI, this result was not changed after analyzing the cases of thermal burns (data not shown). The severity of burns is largely determined by burn area and depth. Major burn size is associated with multiple organ dysfunction and poor prognosis, and burn size is an independent predictor of acute renal failure . In this study, TBSA and full-thickness burns of TBSA strongly correlated with AKI. Patients with hypertension or/and diabetes underwent chronic pathological changes in organs including the heart, brain, kidneys and blood vessels causing deterioration of renal function, and were more predisposed to AKI . Inhalation injury was a severe complication of burn injuries, and was often associated with AKI . Though univariate analysis in this study showed significant difference in inhalation injury between the groups, there was no evidence of an independent inhalation injury effect after adjusting for potential confounders. This result is consistent with recent study . This could be because most mild to moderate inhalation injuries in this study did not develop to ARDS, which was proved to be a risk factor for AKI. ARDS is an important pathophysiologic link between acute lung injury and AKI and the existence of the “lung-kidney crosstalk” [24-26]. Tracheotomy was an independent risk factor for early AKI (OR=2.335, p=0.003) and late AKI (OR=3.708, p=0.003). This can be explained as that the patients with tracheotomy were more seriously ill with inadequate oxygenation and needed mechanical ventilation support. Meanwhile, there may be complications of secondary pulmonary infection induced by tracheotomy and mechanical ventilation. However, we also included a few patients to perform prophylactic tracheotomy for compression of the neck and laryngeal edema after burns.
There are different pathophysiological features and potential mechanisms for burn-related AKI at different stages after burns. Hypovolemic shock is the main complication of major deep burns in the resuscitative phase, with a hugely harmful influence on the whole course of severe burns , when consequent sepsis and MODS increased the mortality accordingly. This study confirmed that hypovolemic shock of early burns is also a risk factor for AKI in severely burned patients. It increased the risk of early AKI, and also increased the risk of late AKI by 9.2 times. It has always been believed that renal hypoperfusion leads to ischemia and ischemia-reperfusion injury, and timely and aggressive fluid resuscitation can reduce the incidence of AKI and improve prognosis . We paid attention to the early fluid resuscitation after burns, and drafted the TMMU protocol for fluid resuscitation in the 1960s, which has been followed to save lives of innumerable burn patients, and until now it is still widely used in China . However, aggressive fluid resuscitation did not completely avoid AKI [30, 31]. Furthermore, excess resuscitation was associated with some complications, including pneumonia, ARDS and elevated compartment syndromes [30, 32]. This study found the earliest onset of AKI was 3h (or may be earlier) after burns, and AKI was still developed in burn patients who received rapid fluid resuscitation, with normal or slight decrease of urine output. Hemorrhagic shock and septic shock in animal experiments demonstrated that immediate fluid resuscitation was sufficient to restore systemic blood pressure but failed to restore renal tissue oxygenation [33, 34]. Therefore, etiology of early AKI is multifactorial, not solely focusing on the amount of fluid received. Renal vasoconstriction by stress-related hormones (catecholamines, angiotensinⅡ, aldosterone, vasopression, etc.), inflammatory mediators, denatured proteins (myoglobin, myoglobinuria, free haemoglobinuria, etc.) are probably also associated with the occurrence of AKI . It was also observed that sepsis was the main reason for late AKI 3 days after burns, and was an independent risk factor for late AKI, which increased the risks of late AKI by 11.8 times. This was consistent with a former study . Interestingly, late AKI occurred before the change of urine volume. On the day of initial diagnosis, urine of patients with late AKI did not decrease (100ml/hour), but sCr increased (156 umol/L). It is likely that renal blood flow did not decrease, but the creatinine clearance has already been markedly reduced. This confirms that the inflammatory mediators and microcirculation dysfunction mainly caused by sepsis and infection contribute to the development of late AKI.
Myohemoglobin (myoglobin) is a harmful product of rhabdomyolysis, which is a clinical syndrome secondary to skeletal muscle injury . Myohemoglobin is the main cause of renal failure. In severely burned patients, myohemoglobin was proved to have a very stable predictive value for AKI with pronounced sensitivity and specificity , as is also reported in other traumatic injuries .
It is interesting to note that decompression escharotomy of circumferential burns probably reduced the risk of AKI development. Circumferential eschar, generally resulted from third-degree burns, can cause compression of the underlying soft tissues as burn edema develops and lead to compartment syndrome . With the increase of the compartment pressure, ischemia of the underlying tissues and the distal tissues will result in tissue and muscle necrosis, and lactic acidosis without timely decompression escharotomy. Toxins released from necrotic tissue are an important etiology of AKI. Decompression escharotomy should be considered earlier, especially in patients with very deep thermal and/or electrical injuries, as it may be effective in the prevention of AKI.
Several studies have emphasized that AKI is independently related to adverse clinical outcomes in trauma patients  and ICU patients . In this cohort, AKI was independently associated with high mortality. Thus, renal dysfunction serves as an additional predictor of huge risk of mortality in severely burned patients.
This study is not a multicenter study, though the total number of AKI patients in the sample far exceeded the recommended number for building a model to provide predictions . This study demonstrated an association between risk factors and AKI occurrence, but has not established causality. Fortunately, the single center study performs a better stability in burn patients’ data managing, diagnosis criteria and treatment, which ensure that the data are more convincible than a multicenter database where subjective factors might be amplified.
A sensitive and specific biomarker for an accurate early diagnosis of AKI is urgently needed even in the absence of subsequent dysfunction. The novel biomarker is probably a produced material of damaged kidney itself, just like the specific cardiac troponin protein produced immediately when myocardial infarction occurs.