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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 4  |  Page : 632-638
Early markers of renal injury in predicting outcome in thermal burn patients

1 Nephrology Department, Mansoura Urology and Nephrology Center, Egypt
2 Plastic Surgery Department, Mansoura University, Egypt

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Date of Web Publication8-Jul-2009


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 2021 Apr 21];20:632-8. Available from: https://www.sjkdt.org/text.asp?2009/20/4/632/53254

   Introduction Top

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 Top

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 Top

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 Top

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.


[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.


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 Top

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.

   References Top

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2.AnLatici R, Ozerdem OR, Dalay C, et al. A retrospective analysis of 1083 Turkish patients with severe burn. Part 2: burn care, survival and mortality. Burns 2002;28(3):239-43.  Back to cited text no. 2    
3.Schiavan M, Di Landro D, Baldo M, et al. A study of renal damage in seriously burned pa­tients. Burn Incl Therm Inj 1988:14(2):107-12.  Back to cited text no. 3    
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16.Lapsley M, Sansom PA, Marlow CT, Flynn FV, Norden AG. Beta 2-glycoprotein-1 (apolipopro­tein H) excretion in chronic renal tubular dis­orders: comparison with other protein markers of tubular malfunction. J Clin Pathol 1991;44 (10):812-6.  Back to cited text no. 16    
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Correspondence Address:
Alaa Sabry
Assistant Professor of Nephrology, Mansoura Urology and Nephrology center, Mansoura University
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