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Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury.

Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, Kielstein JT - Crit Care (2010)

Bottom Line: NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004).Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005).The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg Strasse 1, D-30625, Hannover, Germany. pkuempers@gmx.de

ABSTRACT

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU).

Methods: Serum NGAL (ELISA methodology) was measured in 109 critically ill patients with AKI at inception of RRT in 7 ICUs of a tertiary care university hospital. The primary outcome studied was 28-day mortality. Secondary outcome measures were ICU length of stay, ventilator-free days, and renal recovery at day 28.

Results: There was a significant difference in serum NGAL between healthy subjects (median [interquartile range] 39.0 [37.5-42.75] ng/mL), critically ill patients with systemic inflammatory response syndrome (SIRS) (297 [184-490] ng/mL), and critically ill patients with sepsis (708 [365-1301] ng/mL; P < 0.0001), respectively. Multiple linear regression showed that NGAL levels were independently related to the severity of AKI and the extent of systemic inflammation. NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004). Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005).

Conclusions: This is the first prospective evaluation of serum NGAL as an outcome-specific biomarker in critically ill patients at initiation of RRT. The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.

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Correlation of NGAL serum levels. (a and c). Correlation of NGAL serum levels with sepsis and acute kidney injury (AKI). Bar charts (mean ± standard error of the mean) showing serum neutrophil gelatinase-associated lipocalin (NGAL) levels of critically ill patients with AKI at inception of renal replacement therapy (RRT) stratified by (a) the presence (n = 31) or absence (n = 78) of sepsis as according to the SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions [25], or (c) stratified by the renal variable from the Sequential Organ Failure Assessment (SOFA) score (1 point (n = 9), 2 points (n = 27), 3 points (n = 28), 4 points (n = 45)). (b and d) Scatter plot showing the correlation of serum NGAL concentrations with (c) C reactive protein (CRP) levels, and (d) serum cystatin C levels in critically ill patients at initiation of RRT (n = 109).
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Figure 1: Correlation of NGAL serum levels. (a and c). Correlation of NGAL serum levels with sepsis and acute kidney injury (AKI). Bar charts (mean ± standard error of the mean) showing serum neutrophil gelatinase-associated lipocalin (NGAL) levels of critically ill patients with AKI at inception of renal replacement therapy (RRT) stratified by (a) the presence (n = 31) or absence (n = 78) of sepsis as according to the SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions [25], or (c) stratified by the renal variable from the Sequential Organ Failure Assessment (SOFA) score (1 point (n = 9), 2 points (n = 27), 3 points (n = 28), 4 points (n = 45)). (b and d) Scatter plot showing the correlation of serum NGAL concentrations with (c) C reactive protein (CRP) levels, and (d) serum cystatin C levels in critically ill patients at initiation of RRT (n = 109).

Mentions: Critically ill patients had significantly higher serum NGAL levels at initiation of RRT compared with healthy controls (364 (196 to 582) ng/mL vs. 39.0 (37.5 to 42.75) ng/mL; P < 0.0001). To identify which mediator or index is best related to NGAL, we initially carried out a linear regression analysis for all baseline variables included in Table 1. All variables found to be statistically significant at a 10% level in the simple model were then included in a multiple linear regression model using backward elimination. Using NGAL as the dependent variable, the presence of sepsis, the renal variables from the SOFA score, CRP, and serum cystatin C were independently related to NGAL levels at initiation of RRT (Table 3). As expected, serum NGAL concentrations were significantly higher in patients with sepsis compared with patients without sepsis (834 ± 118 ng/mL (mean ± standard error of the mean (SEM)) vs. 425 ± 57 ng/mL; P < 0.001; Figure 1). No difference was found between patients with SIRS and non-SIRS/sepsis patients (Table 1). Furthermore, serum NGAL steadily increased across groups when stratified by the renal variable from the SOFA score (1 point: 220 ± 42, 2 points: 430 ± 63, 3 points: 489 ± 89, 4 points: 700 ± 114; P = 0.03 by non-parametric ANOVA; Figure 1). The relation of NGAL with these variables was further illustrated by linear correlation analysis, showing that NGAL levels correlated with CRP (r = 0.51; P < 0.0001), and cystatin C (r = 0.39; P < 0.0001) levels, respectively (Figure 1).


Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury.

Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, Kielstein JT - Crit Care (2010)

Correlation of NGAL serum levels. (a and c). Correlation of NGAL serum levels with sepsis and acute kidney injury (AKI). Bar charts (mean ± standard error of the mean) showing serum neutrophil gelatinase-associated lipocalin (NGAL) levels of critically ill patients with AKI at inception of renal replacement therapy (RRT) stratified by (a) the presence (n = 31) or absence (n = 78) of sepsis as according to the SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions [25], or (c) stratified by the renal variable from the Sequential Organ Failure Assessment (SOFA) score (1 point (n = 9), 2 points (n = 27), 3 points (n = 28), 4 points (n = 45)). (b and d) Scatter plot showing the correlation of serum NGAL concentrations with (c) C reactive protein (CRP) levels, and (d) serum cystatin C levels in critically ill patients at initiation of RRT (n = 109).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875521&req=5

Figure 1: Correlation of NGAL serum levels. (a and c). Correlation of NGAL serum levels with sepsis and acute kidney injury (AKI). Bar charts (mean ± standard error of the mean) showing serum neutrophil gelatinase-associated lipocalin (NGAL) levels of critically ill patients with AKI at inception of renal replacement therapy (RRT) stratified by (a) the presence (n = 31) or absence (n = 78) of sepsis as according to the SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions [25], or (c) stratified by the renal variable from the Sequential Organ Failure Assessment (SOFA) score (1 point (n = 9), 2 points (n = 27), 3 points (n = 28), 4 points (n = 45)). (b and d) Scatter plot showing the correlation of serum NGAL concentrations with (c) C reactive protein (CRP) levels, and (d) serum cystatin C levels in critically ill patients at initiation of RRT (n = 109).
Mentions: Critically ill patients had significantly higher serum NGAL levels at initiation of RRT compared with healthy controls (364 (196 to 582) ng/mL vs. 39.0 (37.5 to 42.75) ng/mL; P < 0.0001). To identify which mediator or index is best related to NGAL, we initially carried out a linear regression analysis for all baseline variables included in Table 1. All variables found to be statistically significant at a 10% level in the simple model were then included in a multiple linear regression model using backward elimination. Using NGAL as the dependent variable, the presence of sepsis, the renal variables from the SOFA score, CRP, and serum cystatin C were independently related to NGAL levels at initiation of RRT (Table 3). As expected, serum NGAL concentrations were significantly higher in patients with sepsis compared with patients without sepsis (834 ± 118 ng/mL (mean ± standard error of the mean (SEM)) vs. 425 ± 57 ng/mL; P < 0.001; Figure 1). No difference was found between patients with SIRS and non-SIRS/sepsis patients (Table 1). Furthermore, serum NGAL steadily increased across groups when stratified by the renal variable from the SOFA score (1 point: 220 ± 42, 2 points: 430 ± 63, 3 points: 489 ± 89, 4 points: 700 ± 114; P = 0.03 by non-parametric ANOVA; Figure 1). The relation of NGAL with these variables was further illustrated by linear correlation analysis, showing that NGAL levels correlated with CRP (r = 0.51; P < 0.0001), and cystatin C (r = 0.39; P < 0.0001) levels, respectively (Figure 1).

Bottom Line: NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004).Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005).The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg Strasse 1, D-30625, Hannover, Germany. pkuempers@gmx.de

ABSTRACT

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU).

Methods: Serum NGAL (ELISA methodology) was measured in 109 critically ill patients with AKI at inception of RRT in 7 ICUs of a tertiary care university hospital. The primary outcome studied was 28-day mortality. Secondary outcome measures were ICU length of stay, ventilator-free days, and renal recovery at day 28.

Results: There was a significant difference in serum NGAL between healthy subjects (median [interquartile range] 39.0 [37.5-42.75] ng/mL), critically ill patients with systemic inflammatory response syndrome (SIRS) (297 [184-490] ng/mL), and critically ill patients with sepsis (708 [365-1301] ng/mL; P < 0.0001), respectively. Multiple linear regression showed that NGAL levels were independently related to the severity of AKI and the extent of systemic inflammation. NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004). Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005).

Conclusions: This is the first prospective evaluation of serum NGAL as an outcome-specific biomarker in critically ill patients at initiation of RRT. The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.

Show MeSH
Related in: MedlinePlus