This study was aimed to evaluate renal dysfunction during three weeks after burn injuries. Also we studied the impact of burn size and septicemia on development of acute renal failure. This study was done on 40 major burned patients to evaluate renal efficiency during three weeks postburn. Renal function tests were done for all patients, including serum creatinine, BUN, microalbuminuria, urinary malonaldhyde, fractional excretion of sodium. These tests were done on days 0,3,7,14,21 postburn.
Nine out of 40 patients had experienced ARE They had been diagnosed by rising serum creatinine >2mg/dl and BUN >25mg/dl, and rising of markers of renal damage like microalbuminuria and urinary malonaldhyde (MDA). There was significant relation between burn size, septicemia and increased incidence of ARF
Burns are one of the most serious of all pathologies, also with regard to the surgical and intensive care aspect of treatment [il. Thus burn is not only skin injury but also a serious systemic illness often accompanied by various complications. Acute renal failure (ARF) is one of the major complications of burns, carrying an extremely high mortality [2]. The incidence of ARF in burned patients has been reported to vary from 1 to 30% with mortality rate in these patients ranging from 73 to 100% [2-3]. Despite improved management and the availabilities of dialytic support, mortality rates in burned patients with ARF have remained above 80% [4].
Two different forms of acute renal failure have been described in burned patients, differing in terms of their time of onset. The first (prerenal ARF) occurs during the first few days after injury and is related to hypovolemia. This form of ARF has become less frequent and easily reversed with early energetic fluid resuscitation. The other form of ARF develops later and has more complex pathogenesis. This form has been reported to be related to sepsis and multiorgan failure and is most often fatal and often occurs in larger burn size >45 % [5] .
This study was focused on early diagnosis of ARF occurring in major burns, the latter is defined as second and third degree burn involving 20% or more of body surface area. Early diagnosis helps to put strategy for treatment of ARF in those patients and thus increasing patients' survival. Also we investigated the influence of burn size and the presence of septic manifestation on the occurrence of ARF and patients survival in major burns.
During the year 2004, 40 patients were selected among flame burned patients admitted to the burn unit at Mansoura University Hospital-Egypt. The patients consisted of 17 males and 23 females, their age ranged from 9 to 70 years. Patients had second and third degree burns covering 20% to 70% of their body surface area. They were admitted to our unit within 24 hours of their injuries. Informations of the patients was prospectively analyzed including age, sex, TBSA, cause of injury and burn depth.
All patients were subjected to routine investigation in the form of: Arterial blood gases (ABG) every 12 hours, complete blood count, liver function tests, urine analysis every 5 days. Blood culture, coagulation profile, chest X-rays were done every week. Renal function tests were assessed on day 0,3,7,14 and 21 in the form of serum creatinine, creatinine clearance, in addition to fractional execration of sodium, urinary malonaldehyde (MDA), and micro albuminuria. All patients were resuscitated with crystalloid followed by colloid according to Parkland's formula [6]. The volume was adjusted to produce a mean hourly urine output 50mllh in the first day followed by 100ml/h during the second day postburn.
Patients with previous renal dysfunction, diabetes mellitus, hypertension, or pregnant ladies were generally excluded.
The burn wounds were treated with silver sulphadiazine. Antibiotics were given according to the patients need and culture. Nephrotoxic drugs were generally excluded. Patients underwent thorough investigations for sepsis. Sepsis could be diagnosed by presence of fever, leukocytosis. Blood cultures were done frequently for diagnosis of infection. In patients with sepsis clinical signs were present like tachycardia (HR >90/min.) and tachypnea (RR >20/min.).
Statistical Analysis:
Data are presented as mean ± SD. Statistical analysis was performed using repeated measures ANOVA test using SPSS 6.13 package to compare the patients' characteristics and biological values. Ap-value less than 0.05 was considered statistically significant.
Chi-square was done for categorical factors while continuous factors were compared using MannWhitney test. Stepwise, multiple regression analysis of data was carried out to predict most relevant variable affecting the development of ARF.
A total of 40 patients admitted to our burn unit between 1.05.2004 to 1.12.2004 have entered the study. They had second and third degree burn more than 20% body surface area. Nine out of the 40 patients have experienced ARF. They have been diagnosed by rising serum creatinine >2mg/dl, and blood urea nitrogen (BUN) more than 25mgldl. Serum creatinine and BUN were slightly increased from day 3 postburn until the end of second week, and then gradually increased reaching maximum level at the third week postburn (Fig. 1). In three patients creatinine level increased to reach more than 4mg% and they required dialysis.
Constantly, the group of patients with ARF showed rising of markers of renal damage in the form of appearance of microalbuminuria which progressed to overt proteinuria in 3 cases, and urinary malonaldehyde (MDA) which rose to three folds than basal value indicating glomerular and tubular damage respectively (Figs. 2,3). Fractional excretion of sodium (FENa) was above 2% in all cases that developed ARF indicating acute tubular necrosis (ATN) (Fig. 4).
In the other group of patients that did not develop ARF serum creatinine and BUN levels were decreased to normal on day 3 after being raised on day 0-1 postburn. Other markers of renal damage microalbuminuria and urinary MDA showed transient rise and gradual decline after the second week postburn.
Univariate analysis study of data (Table 1) has shown significant relation between burn size and the incidence of septicemia in both groups. However, there is no impact of burn type, age or sex on incidence of ARF following burn.
Sepsis was noted in almost all patients with ARF, which did not occur within the first 5 days of hospitalization. In our work comparison of patients without renal insult with patients who developed ARF using multiple regression analysis is shown in Table (2). It was found that the most relevant predictive factors for the development of ARF were burned surface area (p<0.0001) and presence of septicaemia (p<0.0371). Also there is significant correlation between burn size and occurrence of septicemia and development of ARF in our patients as shown in Table (3) & Fig. (5).
Extensive cutaneous burn produces local changes which may cause general effects involving every system of the body. Changes in blood volume, fluid exchanges and drug interactions may result in renal damage [7]. This explains why severe burn must be managed not only as dermal injury but also as a serious systemic illness often accompanied by various complications [8]. In this study a prospective study of 40 patients seen over 9 months period at a single burn unit, showed that about one fifth of major burn >20% body surface area patients is complicated by ARF (serum creatinine >2.0 mg/dl). Using multiple regression analysis of data, it was clear that burn size is a highly significant independent risk factor (p<0.0001). Patients with ARF had mean burned surface area of 61%, signifying that wide surface area predisposes to excessive loss of extracellular fluid and albumin, as well as providing good chance of increase of infection hazards.
The above results appear to be compatible with recent reports of Holm et al. [9] and Kim et al. [lo] who studied the correlation between burned BSA and development of ARF. Holm et al. [9] showed that in group of patients with 60-80% burned BSA almost half of the patients developed ARF. Thus, in patients with very severe burns, who survive long enough, renal insufficiency might be a more common occurrence than previously believed.
Univariate and multivariate analysis of data of all patients showed that in addition to surface area burned which is the most important one it was found that the second predictive factor for developing ARF was presence of severe septic complications and was significantly correlated with development of ARF (p<0.0375). This is in accordance with the finding of previous authors [11,12]. So, it is necessary to monitor laboratory and clinical parameters closely for any sign of septicaemia.
The object of laboratory examinations in severe burns is to assess markers of ARF. This help in early diagnosis, management and treatment of ARF aiming to decrease mortality in those patients. In this study we assessed the kidney function postburn by follow up of serum creatinine, recording the fluid balance, and changes in urinary output. Other tests to assess renal function were done like microalbuminuria, urinary MDA, and fractional excretion of sodium. The average concentrations of BUN and serum creatinine have slightly increased during the first 24 hours after burn injury and thereafter were maintained within normal ranges during the 3 weeks post burn in patients without ARF. In ARF patients levels of BUN and serum creatinine showed gradual increase after 3rd day reaching peak value at the end of third week postburn. Serum creatinine was more than 4mgldl in 3 patients necessitating dialytic therapy.
Proteinuria due to renal damage has been studied and it is still regarded as one of the most sensitive markers of the renal injury [13]. Increased albumin excretion usually reflects a glomerular disease but when the quantity is small it may be due to impaired tubular reabsorption of small molecular weight proteins filtered by the glomeruli [14].
This study showed that urinary albumin excretion in burned patients was greater than normal with a peak level on day 3 postburn then fell to normal level in the following 3 weeks after stabilization of hemodynamics parameters of the patients. In ARF patients urinary albumin starts to increase at the end of the first week indicating both glomerular and tubular affection, this was proved by measuring the FENa, which measures the percent of filtered sodium that is excreted in urine. It is an accurate diagnostic test, to differentiate between prerenal ARF and oliguric ATN post burn, which are the most common causes of ARF In burned patients. A value below 1 % suggest prerenal ARF, whereas, a value between 1 and 2% may be seen with either disorder, while a value above 2% indicate ATN [15,16]. In our study we found that FENa was above 2% indicating tubular affection. Proteinuria, high FNa and elevated levels of MDA were reflecting progressive glomerular and tubular dysfunction.
Lipid peroxidation process has been reported to occur initially after thermal trauma [17]. This can lead to severe multiple organ failure [18]. The purpose of this study was to further the time course of this process during burn injury and its effect on renal function. The end products of lipid peroxidation include aldehydes and hydrocarbon gases. The most commonly measured product is malonaldhyde MDA [19]. It has been found that MDA is gross indicator of enhanced lipid peroxidation in renal tubules and is directly proportional to renal damage [20]. In our study we found that 24 hour urinary excretion of MDA was increased on day 0 post burn until the 3rd day, then slightly increased till the end of the 2nd week. In those patients that develop ARF its level was gradually increased after the 2nd week. In the remaining patients (non ARF) the level of urinary MDA continue to decrease to normal after the second week p<0.05.
These results were shown in other studies [8,211. They showed that urinary MDA excretion was greatly increased in burned patients. Its level was 20 times higher than normal during the first week post burn indicating that lipid peroxidation is strongly activated after burn. Increase of urinary MDA in these studies and in our study in ARF patients confirm that urinary MDA appears to be a very sensitive biochemical parameter and may be useful in assessing renal status [22,231, and also suggest that renal inflammation and tubular injury in ARF patients continue after third week post burn.
In conclusion, acute renal failure is a well known complication and dreadful consequence of burns as it may lead to an increase in mortality rate that may approach 80% as proved by many studies. Assessment of renal function in burn should start from day of admission including glomerular and tubular function tests. This helps in early detection of ARF and dealing with those patients in order to improve their outcome.
Future therapeutic strategies that allow a better chance for survival of burn patients who develop ARF should be studied and applied. The newly introduced dialytic techniques as slow continuous arterio-venous and veno-venous hemodiafilteration can help to offer recovery for critically burned patients with cardiovascular compromise or with hypotension. Also, the importance of the use of antioxidants in lessening and prevention of renal damage in burn is also assessed.