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| | | Year : 2009 | Volume : 20 | Issue : 4 | Page : 632-638 | | | Early markers of renal injury in predicting outcome in thermal burn patients | | | Alaa Sabry1, Ihab Wafa1, Ahmed Bahaa El-din2, Al Moddather El-Hadidy2, Mohammed Hassan2
1 Nephrology Department, Mansoura Urology and Nephrology Center, Egypt
2 Plastic Surgery Department, Mansoura University, Egypt
Click here for correspondence address and email | Date of Web Publication | 8-Jul-2009 | | |      | |  Abstract | | | Acute renal failure (ARF) is a well known complication of severe burn and is an important factor that can increase mortality. To determine the predictors of acute renal failure that occur in major burns, we studied 40 patients with moderate to severe thermal burn injury - second to third degree with > 20% of total body surface area. All patients were subjected to routine investigations including: Serum creatinine, blood urea nitrogen, fractional excretion of sodium, urinary malondialdehyde and microalbuminuria on day 0, 3, 7, 14 and 21 of hospitalization. Nine patients (22.5 %) developed acute renal failure; 4 patients required supportive dialysis. The group that developed ARF showed an increase of markers of glomerular damage with appearance of microalbuminuria on day 0 that reached 3 - 4 folds above its normal level on day 14 and remained constant with elevated serum creatinine and burn size in the 3 rd week of ARF, and progressed to overt proteinuria in 3 cases. Urinary malondialdehyde increased 3 folds above normal values before developing acute renal failure, and gradually increased on day 14, which coincided with the increased of microalbuminuria. Two cases (22.2%) in the ARF group who developed septicemia and required dialysis died on the 32 nd and 36 th days post-burn. Burn size and occurrence of septicemia were the only predictors of acute renal failure using multiple regression analysis (P value < 0.001 and < 0.0371, respectively). We conclude that acute renal failure complicates burn patients and is related to the size and depth of burn and occurrence of septicemia. Microalbuminuria and urinary malondialdehyde are useful markers for prediction of renal outcome in such group of patients. How to cite this article:
Sabry A, Wafa I, El-din AB, El-Hadidy A, Hassan M. Early markers of renal injury in predicting outcome in thermal burn patients. Saudi J Kidney Dis Transpl 2009;20:632-8 |
How to cite this URL:
Sabry A, Wafa I, El-din AB, El-Hadidy A, Hassan M. Early markers of renal injury in predicting outcome in thermal burn patients. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2014 Mar 4];20:632-8. Available from: http://www.sjkdt.org/text.asp?2009/20/4/632/53254 |
| Introduction | |  |
With recent advances in the systemic care of burn and understanding the pathophysiology of severe burn injury and systemic inflammatory response syndrome, patients with burn covering up to 80% of their body surface area can frequently survive. [1] Burn is not only skin injury but serious systemic illness often accompanied by various complications. Multi-organ injury complicating severe burn constitutes up to 50% of mortality cases. [2]
Acute renal failure (ARF) that complicates 13-38% of burned patients admitted to hospitals is a well known major complication of severe burn carrying an extremely high mortality. [3] Important predictors of ARF in burn patients include several variables such as occurrence of septicemia, fluid loss, muscle damage, hypotension, cardiopulmonary failure, and use of nephrotoxic agents. [4] ,[5] Furthermore, the development of ARF with delay of intensive management of burn lesion carry a significant negative impact on survival of burn patients. [6]
Renal insults in burns are characterized by the development of extensive inflammation inducing an intensive acute phase response in the kidney. Burn injury initiates a significant oxidative stress that induces ARF as well as multiorgan failure. [7] Creatinine clearance, microalbuminuria, and urinary malondialdehyde (MDA) are used to assess the presence of both glomerular and tubular injury.
We aim in this study to evaluate the development and various prognostic and predictive factors of ARF in thermal burn patients in addition to early therapeutic interventions.
| Materials and Methods | | |
We studied patients with moderate to severe thermal burn injury - second and third degree burns covering 20 to 70% of their body surface area (BSA). Patients with previous renal dysfunction, diabetics, hypertensives and pregnant patients were excluded from our study.
The study patients were admitted to Mansoura Emergency Hospital within 24 hours of their injury. All the patients were resuscitated with crystalloids followed by colloids according to the Parkland formula (4 mL/kg/%BSA/first 24 hours); colloids were given as albumin, fresh frozen plasma during the next 24 hours. The infusion volume was adjusted to produce a mean hourly urine output of 50 mL/h during the first 24 hours and 100 mL/h during the second 24 hours after insertion of a Foley's catheter.
The burn wounds were thoroughly and gently cleaned by immersing the patients in a whirlpool bath to which sodium hypochlorite had been added (150:1). The wounds were then debrided by a surgical sponge, rinsed, dried and 1 % silver sulfadiazine cream was applied and then covered with dry coarse mesh gauze; this procedure was daily repeated. Surgical treatment included early excision and grafting with autografts as indicated.
Catecholamines were administered when appropriate to maintain sufficient hemodynamic stability. Antibiotic were administered according to the clinical condition and cultures' results with avoidance of nephrotoxic drugs. Nutritional support aimed to maintain a positive nitrogen balance by greater than 6 g/day.
All the patients were subjected to routine investigations. Arterial blood gases were done twice daily, complete blood count, liver function, blood culture, coagulation profile, and plain chest X-ray were done every week. Urinalysis, serum creatinine, blood urea nitrogen (BUN), fractional excretion of sodium, urinary Malondialdehyde (MDA) and microalbuminuria was done on day 0, 3, 7, 14 and 21. All samples were analyzed in duplicate. MDA was isolated and quantified according to Guichardant et al, 1994 [8] on SPEKOLL 11 using the following equation: Test/standard × concentration of test. Urinary microalbuminuria was defined by albumin excretion rate between (30-300 mg/day) determined by radioimmunoassay using (Org SMA Immunoassay procedure kit Orgenetic Diagnostika GmbH, Mainz).
We calculated fractional excretion of sodium (FENa) according to the following formula:
Where UNa: urinary sodium, UCr: Urinary creatinine, PNa: Plasma sodium, and PCr: Plasma creatinine. A value below 1% was considered as prerenal and > 2% as renal ARF in oliguric patients.
Dialysis was initiated with a rising serum creatinine level > 4 mg/dL and BUN > 200 mg/dL or in patients with anuria or oliguria (urine volume < 400 mL/24 hour) with anasarca and/or hyperkalemia.
Sepsis was defined as a blood culture revealing the pathogen during the hospital stay or at autopsy.
| Statistical Analysis | | |
We performed the analysis of data using the SPSS for windows software package release 11. Data are presented as mean ± standard deviation. Student "t" test and chi square test were applied where appropriate. Stepwise multiple regression analysis of data was carried out to predict most relevant variable affecting the development of ARF. A P value of < 0 .05 was considered significant.
| Results | | |
A total of 40 patients (17 men and 23 women with age range from 9-70 years) met our inclusion criteria for the study during the period from May to December 2005. Characteristics and demographics of patients who developed and those who did not develop ARF are presented in [Table 1].
Parameters of the ARF and non-ARF groups are shown in [Table 2]. Nine (22.5%) patients developed ARF (defined by rising of serum creatinine > 2 mg/dL and blood urea nitrogen (BUN) > 25 mg/dL) during the 3 rd week of hospitalization and coincided with the occurrence of septicemia. The parameters of renal failure gradually increased from day 7 post burn until the end of second week reaching maximum level at the third week after burn. Four patients required supportive dialysis as their serum creatinine exceeds 4 mg/dL. Patients who did not develop ARF were early resuscitated from the start and received all supporting measures that maintain the renal function and improve hemodynamic parameters. Their serum creatinine and BUN levels were within normal levels at different time intervals of the study. Univariate analysis study of data has shown no impact of burn type, age, sex on incidence of ARF following burn.
Microalbuminuria
[Figure 1] shows the course of microalbuminuria in the ARF and Non ARF groups. The ARF group developed microalbuminuria from day 0 of hospitalization that reached up to 3 or 4 fold above normal limit on day 14 and up to a maximum level on day 21. This pattern was consistent with elevations of serum creatinine and BUN. Microalbuminuria progressed to overt proteinuria in 3 cases in the ARF group.
Urinary MDA
[Figure 2] shows the course of the urinary MDA, which was elevated in the ARF group about 3 folds above normal value on day 0, and gradually increased on day 14 reaching maximal level on day 21.
Fractional excretion of Na
In all cases that developed acute renal failure FENa was above 2% indicating ATN.
Incidence of septicemia
All the ARF patients experienced septicemia during the 3 rd week in contrast to only 10 (30%) in the non-ARF group. The microbiological analysis revealed Staph aureus in 14 patients, pseu domonas aeroginosa in 6 patients, Klebsilla species in 4 patients, Acinetobacter in 2 patients, Streptococcus in 2 patients and Candida albicans in one patient, respectively.
Mortality
Two cases (22.2%) in ARF group died on days 32 nd and 36 th after burn injury. Both cases were septicemic and required dialysis support.
Predictors of ARF
Burn size % and occurrence of septicemia were the only predictors of ARF in burn patients by multiple regression analysis (SE B 0.003 and 0.104- P value 0.001 and .0371 respectively).
| Discussion | | |
The incidence of ARF in our study was 22.5%, which is relatively higher than what is reported in other studies. [9] ,[10] However the incidence of ARF after thermal injuries appears variable according to what has been reported in the literature. [4] This could be explained by the variable severity of the burns and on the definition of ARF. The higher burn size in our study- (>_ 61%) could partially contribute to the high incidence of ARF.
ARF can be immediate or late after thermal burn injury. ARF that occurs immediately after burns, which is related to extensive fluid losses from the burn wounds and/or a delay in fluid resuscitation that results in decreased renal perfusion. [6] Furthermore, burn stress and its associated circulatory derangement stimulate the release of stress-related hormones, such as catecholamine, angiotensin II, aldosterone, and vasopressin. [6],[7],[8],[9],[10] These hormonal changes cause vasoconstriction and disturbed regional blood flow in the kidneys. [11] On the other hand, the late appearance of ARF is mainly associated with systemic sepsis, and is usually accompanied by other organ failure such as pulmonary insufficiency, liver failure, or disseminated intravascular coagulopathy. [11] This late ARF is associated with increased serum levels of cytokines (tumor necrosis factor, interleukin 1, etc), eicosanoids (prostaglandins, thromboxane and leukotrienes), and stress-related hormones that cause vasoconstriction, fluid retention, and renal hypoperfusion resulting in tubular necrosis. [6],[7],[8],[9],[10],[11],[12] The administration of nephrotoxic antibiotics, such as aminoglycosides and certain cephalosporins in treating burn infections, is another factor that may cause ARF. [13]
The vasodilator prostaglandin E2 is found in the kidneys and counteracts the effect of many vasoconstrictors. Its production, however, is inhibited in the early phase of burns and when sepsis develops. [6] ,[11] ,[13] Other circulating media tors that originate from the burn wound such as IL-6, IL-8, and tumor necrosis factor, contribute to the hypermetabolic and inflammatory response in burned patients. [14] Although these mediators were not examined in our study, we cannot deny their rule.
Fractional excretion of sodium (FENa) is an accurate screening tool to differentiate between prerenal azotemia and acute tubular necrosis (ATN) which are the commonest causes of ARF in burn patients. We found FENa more than 2% in those patients who developed ARF indicating ATN.
Increased urinary excretion of protein is one of the most common and easily detected signs of renal pathology; alteration may occur both in quantity and composition of urinary proteins. [15] Microalbuminuria is still regarded as one of the most sensitive markers that reflect glomerular injury. [16] In our study, microalbuminuria was maximal on the day of admission and decreased gradually thereafter in patients who did not develop ARF, while there was a constant rise of albuminuria in patients who developed ARF after the second week, coincided with the development of septicemia. These results are in concordance to what reported by Kang HK et al, [17] and supported by data from animal and clinical studies demonstrating that burn shock manifests lesions in the renal tubules and glomeruli with high and low-molecular weight proteins appearing in the urine. [6],[7],[8],[9],[10],[11],[12]
It is known that burn injury initiates an appreciable oxidative stress and inflammation leading to severe multiple organ failure. [7] Free radical production is associated with inflammation and circulating lipid peroxides increase in burn patients during the first week post injury. [18] Oxidants are major products of inflammation and lipids peroxides increase in the plasma of burn animals and patients. [7] ,[19]
The end products of lipid peroxidation include aldehydes and hydrocarbon gases. The most commonly measured product is MDA, which is known to react with proteins and amino acids. [20] Urinary MDA is a gross indicator of enhanced lipid peroxidation in renal tubules and directly proportional to renal damage. [21] There is a close relationship between the intensity of lipid peroxidation and complications after burns. [22] In our study 24-hour urinary excretion of MDA was increased in all patients who developed ARF, while it gradually decreased in those who did not develop ARF, confirming that lipid peroxidation is strongly activated after burns. We can suggest that renal inflammation and tubular injury in burned patients persist during the first 3 weeks after the burn injury in spite of early and aggressive management. These results are in agreement with what reported in earlier studies. [15] ,[17] This pattern of changes in the urinary MDA appears to be a very sensitive biochemical parameter and may be a useful in the assessment of renal status. [8],[9],[10],[11],[12],[13],[14],[15],[16],[17]
Sepsis is a major factor that contributes to mortality in burned children with acute renal failure. [23] Moreover, fluid resuscitation and prevention of sepsis can reduce the incidence of ARF in burned adults. [24] In our study, all cases that developed ARF and 30% in cases with normal renal function, developed sepsis, which coincides with the report by Brive et al, [25] and is higher than that the 1% reported by Jeschke et al [26] and less than 91% reported by Holm. [4] This variability in incidence of sepsis may be due to variability of severity and size of the burns. Multiple regression analysis of our cases showed that burned body surface area was highly significantly independent risk factor for development of ARF and incidence of sepsis, whereas age, third degree burn or electric injury was not significant. This is in accordance with the findings of previous studies. [1] ,[2] ,[27] The second predictive factor for developing ARF, in addition to surface area burned, was the presence of sever sepsis as was demonstrated by other authors. [9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28]
Once ARF develops, the prognosis of the burn patient becomes remarkably unfavorable, as most studies have reported a mortality rate of around 80%. However, there is a trend toward a lower mortality in burned patients with ARF in recent years. [29] In our study, the mortality rate in patients with ARF was 22.9%, and due to multiple organ failure. However, no firm conclusion can be drawn because of the small number of patients. Interestingly, survivors almost uniformly recovered to a normal renal function levels.
In conclusion, ARF was found in 22.5 % of burn patients and correlated with the size and depth of the burns. Development of septicemia after burn can trigger a series of inflammatory reactions and mediators that lead to multiple organ dysfunctions including renal damage. Microalbuminuria and urinary MDA are good early markers for prediction of ARF in burn patients. Minimizing renal damage in burn depends on the integrated efforts of early and rapid resuscitation and early diagnosis of renal injury.
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Correspondence Address:
Alaa Sabry
Assistant Professor of Nephrology, Mansoura Urology and Nephrology center, Mansoura University
Egypt
PMID: 19587506
[Figure 1], [Figure 2]
[Table 1], [Table 2] | |
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