Diagnostic performance of plasma and urine neutrophil gelatinase-associated lipocalin, cystatin C, and creatinine for acute kidney injury in burn patients: A prospective cohort study.

BACKGROUND: Diagnosing acute kidney injury quickly is imperative since it is known as an independent risk factor for mortality in burn patients. We evaluated the diagnostic power of creatinine, cystatin, serum and urine neutrophil gelatinase-associated lipocalin at different time periods and observed the changes from baseline for each biomarker. METHODS: This was a prospective observation study from January 2015 to February 2016. A total of 84 patients were enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th, 21st, and 28th days after admission. All samples were collected until acute kidney injury developed. RESULTS: Acute kidney injury developed in 35 patients. The mean age was 49.6 years with a male predominance. The median urine neutrophil gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88 mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL) on the 14th day. The area under the curve of creatinine levels was the highest with 0.857 during the 1st week. The area under the curve of urine neutrophil gelatinase-associated lipocalin was the highest with 0.803 during the 5th week. CONCLUSIONS: Within 1 week of acute kidney injury, creatinine level was the optimal biomarker for diagnosis while urine neutrophil gelatinase-associated lipocalin showed better diagnostic performance following the 4- week period.

Assessment of Plasma Neutrophil Gelatinase-Associated Lipocalin for Early Detection of Acute Kidney Injury and Prediction of Mortality in Severely Burned Patients.

The purpose of this study was to assess the plasma neutrophil gelatinase-associated lipocalin (NGAL) for early detection of acute kidney injury (AKI) and prediction of mortality in severely burned patients. From January 2014 to September 2015, 76 consecutive patients with more than 20% of TBSA burned were enrolled. Blood samples for plasma NGAL were collected at 0, 7, 14, 21, and 28 days after admission and analyzed with injury severity, clinical outcome, and AKI development. Plasma NGAL was significantly affected by the TBSA burned, AKI, and mortality, and it was significantly increased after operation and septic shock. Plasma NGAL was significantly increased within 7 days before AKI development in total patients (P < .001) and septic shock patients (P < .001) but not significantly increased in patients without septic shock (P = .167). Though, in a receiver operating characteristic curve analysis for predicting AKI, continuous renal replacement therapy application, and mortality, plasma NGAL was statistically significant; plasma NGAL was not independently associated with mortality in a multivariate logistic regression analysis. Plasma NGAL should be interpreted carefully in the major burn patients because it can reflect both inflammatory condition and AKI.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.

BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.

Evaluation of diagnostic biomarkers for acute kidney injury in major burn patients.

PURPOSE: Acute kidney injury (AKI) in major burn patients is a common complication with high morbidity and mortality. The mainstream treatment is early diagnosis and rapid termination and prevention of the underlying insult. Therefore, it's essential to identify early biomarkers predicting AKI. METHODS: A total of 85 patients who were admitted to the burn intensive care unit from June 2012 to July 2013 were included in this prospective cohort study. Ten biomarkers (blood urea nitrogen, serum creatinine, urine creatinine, cystatin C, cystatin C glomerular filtration rate, AST, lacate dehydrogenase [LD], creatine kinase, lactic acid, and myoglobin) were obtained at time of admission and evaluated as diagnostic biomarkers to predicting AKI and early AKI. RESULTS: Out of 85 patients, 35 patients were dead and overall mortality was 41.2%. The mean age was 49.4 years and mean percentage of total body surface area was 53.2%. Area under the curve (AUC) of receiver operating characteristic curve of biomarkers on predicting AKI were 0.746, 0.718, and 0.717 in LD, lactic acid, and serum creatinine, respectively. AUC of cystatin C predicting AKI was much lower at 0.555. AUC of biomarkers on predicting early AKI were 0.833, 0.816, 0.790, and 0.759 in LD, serum creatinine, AST, and serum myoglobin. CONCLUSION: LD, lactic acid and serum creatinine were acceptable as diagnostic biomarkers of AKI and LD, serum creatinine, AST, and serum myoglobin were reasonable as diagnostic biomarkers of early AKI. However, cystatin C was an unfavorable biomarker in major burn patients.

Serum cystatin C and microalbuminuria in burn patients with acute kidney injury.

BACKGROUND: This study was aimed at evaluating the effectiveness of serum cystatin C and microalbuminuria as diagnostic markers for acute kidney injury (AKI) in major burn patients. MATERIALS AND METHODS: Major burn adult patients admitted to the burn intensive care unit within 24 h from the onset of injury were enrolled. Serum cystatin C and microalbuminuria (albumin-creatinine ratio, ACR) were obtained at postburn days 1, 3, 7, 14, 21 and 28. The patients were divided into two groups of the AKI group and the nonacute kidney injury group. RESULTS: A total of 97 patients were enrolled in this study. Acute kidney injury was diagnosed in 40 patients (41.2%) at postburn day 17.3 ± 7.9. The area under the curve of the receiver operating characteristic curve for serum cystatin C was 0.808 (95% CI, 0.711-0.905, P < 0.001) at postburn day 7 and 0.908 (95% CI, 0.843-0.973, P < 0.001) at postburn day 14. The results were 0.610 (95% CI, 0.497-0.724, P = 0.069) for ACR at postburn day 7 and 0.694 (95% CI, 0.589-0.798, P = 0.001) at postburn day 14. The optimal cut-off value of serum cystatin C at postburn day 14 and ACR at postburn day 14 were 0.85 mg/L (sensitivity, 89.5%; specificity, 82.5%) and 41.51 mg/g cre (sensitivity, 60.5%; specificity, 61.4%), respectively. Serum cystatin C at postburn day 14 was the only significant factor in relation to AKI. CONCLUSIONS: Serum cystatin C is a valuable diagnostic marker, whereas microalbuminuria is a relatively less significant marker for AKI in major burn patients.

The application of cultured epithelial autografts improves survival in burns.

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006-2013, total 177 massive-burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi-square test. Multivariate logistic regression, Kaplan-Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft-application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet-type and spray-type CEA groups. Allograft application (odds ratio, 4.44; p < 0.01) significantly influenced CEA application. The CEA group showed significantly higher survival rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p = 0.02) and 0.59 (p = 0.05) according to the uni- and multivariate Cox regression analysis, respectively. In conclusion, early and aggressive allograft application is required to facilitate CEA application. Furthermore, the use of CEAs was associated with a lower mortality, but this result should be interpreted with caution as the groups were not randomized.

Assessment of biochemical markers in the early post-burn period for predicting acute kidney injury and mortality in patients with major burn injury: comparison of serum creatinine, serum cystatin-C, plasma and urine neutrophil gelatinase-associated lipocalin.

INTRODUCTION: The reported mortality rates range from 28% to 100% in burn patients who develop acute kidney injury (AKI) and from 50% to 100% among such patients treated with renal replacement therapy. Recently, the serum cystatin C and plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels have been introduced as early biomarkers for AKI; the levels of these biomarkers are known to increase 24 to 48 hours before the serum creatinine levels increase. In this study, we aimed to estimate the diagnostic utility of the cystatin C and plasma and urine NGAL levels in the early post-burn period as biomarkers for predicting AKI and mortality in patients with major burn injuries. METHODS: From May 2011 to July 2012, 90 consecutive patients with a burn wound area comprising ≥ 20% of the total body surface area (TBSA) were enrolled in this study. Whole blood and urine samples were obtained for measuring the serum creatinine, serum cystatin C, and urine and plasma NGAL levels at 0, 3, 6, 12, 24, and 48 hours after admission. Receiver operating characteristic curve, area under the curve, and multivariate logistic regression analyses were performed to assess the predictive values of these biomarkers for AKI and mortality. RESULTS: In the multivariate logistic regression analysis, all variables, including age, percentage TBSA burned, sex, inhalation injury, and serum creatinine levels, serum cystatin C levels, and plasma and urine NGAL levels were independently associated with AKI development. Moreover, age, sex, percentage TBSA burned, and plasma and urine NGAL levels were independently associated with mortality. However, inhalation injury and the serum creatinine and cystatin C levels were not independently associated with mortality. CONCLUSIONS: Massively burned patients who maintained high plasma and urine NGAL levels until 12 hours after admission were at the risk of developing early AKI and early mortality with burn shock. However, the plasma and urine NGAL levels in the early post-burn period failed to predict late AKI and non-burn shock mortality in this study. Nevertheless, the plasma and urine NGAL levels were independently associated with AKI development and mortality within 48 hours after admission.

Change of serum phosphate level and clinical outcome of hypophosphatemia in massive burn patient.

BACKGROUND: Hypophosphatemia is relatively common phenomenon in patients with massive burn injury. Therefore, we check serum phosphate level routinely and try to supply phosphate in a timely manner. The purpose of this study was to investigate the change of the serum phosphate level of early postburn period and the impact of hypophosphatemia on the prognosis of patients. METHODS: A total of 227 patients with burn injury were reviewed retrospectively. We performed analysis of serum phosphate level within 20 days from burn injury. RESULTS: Patients' mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate < 1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia (1.0 ≤ phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore, overall incidence of hypophosphatemia was 66.4%. There was no significant difference in serum phosphate level with survival, total body surface area burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence interval [CI], 1.025-9.871; p = 0.045), total body surface area burned (OR, 20.934; 95% CI, 6.845-64.024; p = 0.000), and mechanical ventilation (OR, 5.581; 95% CI, 2.380-13.085; p = 0.002) were independently associated with mortality. However, serum phosphate level (OR, 0.828; 95% CI, 0.275-2.495; p = 0.737) does not have a statistical significance. CONCLUSION: Although multiple studies have evaluated the efficacy and safety of phosphate repletion regimens, the effect on mortality and morbidity is not well reported. However, our results show that patients with massive burn injury have high incidence of hypophosphatemia, and hypophosphatemia can result in many complications. Therefore, routine check and supply of phosphate can be suggested in patients with massive burn injury. LEVEL OF EVIDENCE: Prognostic study, level II.

Changes in the levels of interleukins 6, 8, and 10, tumor necrosis factor alpha, and granulocyte-colony stimulating factor in Korean burn patients: relation to burn size and postburn time.

BACKGROUND: Major burn injury induces an inflammatory response that is accompanied by the release of various cytokines. We investigated the gradual changes in the levels of pro-inflammatory and anti-inflammatory cytokines following burn injury and determined the relationship between these levels and burn size in adult Korean patients with burn injury. METHODS: Blood samples from 9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7, 14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF) were measured. Burn patients were divided into 3 groups according to burn size (15-30%, 31-50%, >50% total body surface area), and the concentrations of the cytokines were compared between these groups and the control group over 3 weeks. RESULTS: Compared to their levels in controls, IL-6, IL-8, IL-10, TNF-α, and G-CSF levels in burn patients were significantly higher during the observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time point increased with burn size, although peak levels and time to peak levels of these cytokines differed from patient to patient. CONCLUSIONS: These findings indicate that IL-6, IL-8, IL-10, TNF-α, and G-CSF are important mediators in inflammatory changes after burn injury; however, various factors, including burn size, may influence the concentrations of these cytokines.

Prediction of clinical outcomes for massively-burned patients via serum transthyretin levels in the early postburn period.

BACKGROUND: We observed that serum transthyretin (TTR) levels consistently remain low when patients' general conditions are poor, despite adequate nutritional support. We conducted this study to analyze the changes of serum TTR over time from injury in massively-burned patients and verify the validity of prediction by clinical outcomes, which are assessed via serum TTR in the early postburn period. METHODS: From January 2005 to December 2010, the samples of serum TTR from 471 burn patients (mean % total body surface area [TBSA] burned, 51% ± 20%) were analyzed with time frames from injury retrospectively. RESULTS: Serum TTR significantly decreased during the period from day 5 to day 10 postinjury in both the survival group (n = 290, mean %TBSA burned, 42.9% ± 14.2%) and nonsurvival group (n = 181, mean %TBSA burned, 64.6% ± 20.8%). However, after this period, the serum TTR constantly increased in the survival group but remained low in nonsurvivors. At all time, the levels of serum TTR obtained from survivors were significantly higher than those of nonsurvivors. The serum TTR had weak correlation with the extent of the burn injury (r = -0.234). Survival rates of the patients increased significantly by the increase of the serum TTR of early postburn period. In multivariable model, age (odds ratio [OR], 1.054; 95% confidence interval [CI], 1.043-1.066; p = 0.000), TBSA burned (OR, 1.058; 95% CI, 1.051-1.066; p = 0.000), sex (OR, 0.720; 95% CI, 0.547-0.947; p = 0.019), and serum TTR during early postburn period (OR, 1.05; 95% CI, 0.873-0.972; p = 0.003) were independently associated with mortality. CONCLUSIONS: The serum TTR of early postburn period can be used as a prognostic markers, and low serum TTR can be used as a signal for screening out the patients at risk who need careful assessment and monitoring at an early stage.

Clinical study of cultured epithelial autografts in liquid suspension in severe burn patients.

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases.