Preoperative Urinary Neutrophil Gelatinase-Associated Lipocalin and Outcome in High-Risk Heart Failure Patients Undergoing Cardiac Surgery Simona Silvetti, MD,* Roberta Meroni, MD,* Elena Bignami, MD,* Tiziana Bove, MD,* Giovanni Landoni, MD,* Alberto Zangrillo, MD,* Rinaldo Bellomo, MD,† and Federico Pappalardo, MD* Objective: To investigate the ability of early urinary neutrophil gelatinase-associated lipocalin to predict postoperative complications in adult patients with ventricular dysfunction undergoing cardiac surgery. Design: Prospective observational study. Setting: Single-center study, university hospital. Participants: Fifty-six adult high-risk cardiac surgical patients with preoperative cardiac failure. Interventions: None. Measurements and Main Results: Demographic and clinical characteristics were obtained, and neutrophil gelatinase-associated lipocalin was measured at baseline and at several time points after surgery. Patient characteristics and neutrophil gelatinase-associated lipocalin levels were related to renal and patient outcome. On multivariate

analyses, preoperative urinary neutrophil gelatinaseassociated lipocalin was an independent predictor of length of intensive care stay (p ¼ 0.004) and in-hospital stay (p ¼ 0.04), but not of acute kidney injury or renal replacement therapy and was not associated with baseline renal function. Conclusions: In a cohort of high-risk cardiac surgery patients, preoperative urinary neutrophil gelatinaseassociated lipocalin value provided prognostic information that was independent of the onset of acute kidney injury or of preoperative renal function. & 2014 Elsevier Inc. All rights reserved.

D

the following criteria: Tricuspid annular plane systolic excursion o15 mm or tissue Doppler imaging of the tricuspid annulus o10 cm/ second, echocardiographic evidence of systemic venous congestion or severe pulmonary hypertension (pulmonary artery systolic pressure 460 mmHg), or severe tricuspid regurgitation. Baseline demographics, comorbidities (reintervention, diabetes, and chronic renal failure defined as baseline creatinine 41.5 mg/dL or estimated glomerular filtration rate (eGFR) o40 mL/min), information on intraoperative characteristics such type of surgery, duration of cardiopulmonary bypass (CPB), and aortic cross-clamp time were collected for each patient. The European System for Cardiac Operative Risk Evaluation (EuroSCORE)17 was calculated. To measure uNGAL, 5 mL of urine were collected at the following time points: Baseline (T0 ¼ before cardiac surgery), at ICU arrival after surgery (T1), and the day after the surgery. The T0 sample of each patient was collected and stored at – 701C waiting for the T1 sample to analyze them together (6-8 h after T0 sample)”. Urine collection was performed directly from the drainage tube to avoid mixing with urine produced at other times during ICU stay. Simultaneously, serum creatinine, creatinine clearance, and troponin T were measured at each time point. eGFR at baseline was calculated using the standard four-variables of the Modification of Diet in Renal Disease (MDRD) equation. Postoperative outcomes included low-cardiac-output syndrome (LCOS) defined as the need for Z20 inotrope units. This inotrope unit score attempted to quantify the amount of inotropic support provided in the postoperative period, assigning an arbitrary equivalent:

ESPITE ADVANCES in anesthesia, operative techniques, and supportive care, acute kidney injury (AKI) continues to be an important complication of cardiac surgery. In different studies, its incidence was widely variable, ranging from 7.7% to 28.1%, probably because of the different criteria used to define “renal dysfunction.”1 Moreover, AKI after cardiac surgery is a major contributor to intensive care unit (ICU) and hospital stay (LOS), costs, and mortality.2 Patients undergoing cardiac surgery are at very high risk of AKI. They often are subjected to preoperative conditions that predispose them to kidney damage, particularly renal hypoperfusion and drugs. Furthermore cardiopulmonary bypass (CPB) may further damage the kidney via hemodynamic changes and the activation of the coagulation/inflammation cascades. Multiple studies have suggested recently that serum neutrophil gelatinase-associated lipocalin (NGAL) levels in patients after cardiac surgery can be used to estimate the risk of early worsening of renal function.3–5 Similarly, postoperative urinary NGAL (uNGAL) has been reported to be an early predictor of AKI3,4–11 and of survival12–16 in cohorts of heterogenous cardiac surgery patients. However, limited data exist on its preoperative value as a predictor of outcome.5,13 The authors previously measured urinary NGAL in a small heterogenous adult cardiac surgical population (27 patients not included in this study) and found that urinary uNGAL at 24 hours after surgery was associated with length of ICU stay.14 In light of these data and to evaluate uNGAL as a mechanism to identify preventive strategies, the authors aimed to study the role of early uNGAL in the prediction of outcome in very-high-risk cardiac surgery patients. MATERIAL AND METHODS After ethics committee approval and patients’ written consent, consecutive cardiac surgical patients at high risk of postoperative left and/or right cardiac dysfunction were studied. Patients were considered at risk for left ventricular dysfunction if they had preoperative left ventricular ejection fraction o45% and at risk for right ventricular dysfunction if undergoing right-sided heart surgery with at least one of

KEY WORDS: neutrophil gelatinase-associated lipocalin, intensive care, acute kidney injury, cardiac surgery

From the *Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy; and †Departments of Intensive Care and Cardiac Surgery, Austin Health, Melbourne, Australia. Address reprint requests to Giovanni Landoni, MD, Department of Anesthesia and Intensive Care, Istituto Scientifico San Raffaele, Milano, Italia, Via Olgettina 60 Milano, 20132 Italy. E-mail: landoni. [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.07.007

Journal of Cardiothoracic and Vascular Anesthesia, Vol 28, No 2 (April), 2014: pp 323–327

323

324

SILVETTI ET AL

Dopamine μg/kg/min  1 + dobutamine μg/kg/min  1 + epinephrine or norepinephrine μg/kg/min  100,18 levosimendan or enoximone μg/ kg/min  1.5 (for example, 5 μg/kg/min of dobutamine or dopamine ¼ 5  1 ¼ 5 points of inotropic score; +0.05 μg/kg/min of epinephrine or norepinephrine ¼ 0.05  100 ¼ 5 points of inotropic score; 5 μg/kg/ min of levosimendan or enoximone ¼ 5  1.5 ¼ 7.5 points of inotropic score). LCOS also was defined by the use of the intra-aortic balloon pump (IABP) and the need for extracorporeal membrane oxygenation (ECMO). Renal dysfunction was defined according to the RIFLE criteria, change in blood creatinine level or GFR or oliguria from a baseline value over one week.19 The need for continuous venovenous hemofiltration (CVVH) and the length of ICU stay, length of stay in hospital, and hospital mortality also were recorded. All patients underwent preoperative clinical evaluation, routine blood tests (blood cell count, coagulation, electrolytes, liver and renal function), resting ECG, chest X-ray, and transesophageal echocardiography. Patients 440 years old or with typical history underwent coronary angiography before surgery. Preoperative therapy was administered until the day of surgery with the exception of aspirin, suspended a week before the procedure, and ACE inhibitors, imbricate at the time of hospitalization with shorter half-life drugs. All patients received a standardized anesthetic management. Urinary samples were assessed using the Abbott ARCHITECT i1000 (Abbott Diagnostic, Roma, Italy); the architect uNGAL assay is a chemiluminescent microparticle immunoassay for the quantitative detection of NGAL in human urine. This assay has a functional sensitivity of 10 ng/mL, with a total coefficient of variation of 10%. The measurement was performed by an internal laboratory. The aim of this study was to evaluate the role of early uNGAL in the prediction of outcome in very-high-risk cardiac surgery patients. Power and sample size determination were measured by the coefficient of linear correlation between the baseline NGAL and the ICU stay. The testing procedure was as follows: A sample size of 50 achieved 83% power to detect a difference of –0.40 between the null hypothesis correlation of 0.00000 and the alternative hypothesis correlation of 0.40 using a two-sided hypothesis test with a significance level of 0.05. The minimum expected difference reflects the difference between the upper and lower limit of an expected confidence interval. In this study, a 95% CI indicated the range in which 95% of results would fall if the study were to be repeated an infinite number of times, with each repetition including 56 patients specified by the sample size. From the authors’ experience, it was supposed a mean ICU stay of 7 days and a standard deviation (SD) for the ICU stay of 5 days. Based on these assumptions, the 95% CI was 5.6-8.3. Therefore, 56 patients had to be examined in the study. Categoric variables are expressed as numbers and percentages, whereas continuous variables are shown as mean ⫾ standard deviation or as median and interquartile range according to normality of distribution (Shapiro-Wilk and Kolmogorov-Smirnov). A generalized linear model was used to identify predictors of ICU stay, of hospital stay, and of preoperative NGAL. All associations were assessed first by means of univariate model. In the multivariate analysis, the authors included all the variables that were statistically associated with the outcomes of interest with a p value r0.2 at the univariate models. The best multivariate model was selected by stepwise selection method, and the statistical significance was set at the two-tailed 0.05 level. Data were analyzed with SAS 9.2 (SAS Institute Inc. Cary, NC). RESULTS

The preoperative characteristics of the 56 enrolled patients are summarized in Table 1. Notably, 21 (37.5%) patients had

reoperations, 21 (37.5%) underwent multiple valve surgery, and all patients had either right (34 patients) or left (11 patients) preoperative ventricular dysfunction, or both (11 patients). Mean ejection fraction in the 22 patients with left ventricular dysfunction was 33% + 8.0%, and in the patients with isolated right ventricular dysfunction, it was 58% + 7.0%. Postoperatively, all patients received inotropic agents (epinephrine, enoximone, levosimendan, dobutamine, or dopamine) or vasopressors (norepinephrine), with 20 (36%) of them receiving an IABP (7 preoperatively, 7 intraoperatively, and 6 postoperatively) and two (3.6%) treated with ECMO (Table 1). Twenty-nine (51.8%) patients developed AKI, with three requiring renal replacement therapy (RRT). Twenty-two AKI patients (75.8%) recovered from AKI at hospital discharge (return to baseline renal function), four AKI patients died (13.8%), and three (11.4%) were discharged with impaired renal function. Overall, six patients died during hospitalization (10.7%). The results of the univariate model showed that the statistically significant predictors of ICU stay (Table 2) were EuroSCORE (regression coefficient ¼ 0.34, standard error ¼ 0.05, p ¼ o0.001), diabetes (regression coefficient ¼ 7.04, standard error ¼ 2.21, p ¼ 0.003), AKI (regression coefficient ¼ 4.52, standard error ¼ 1.50, p ¼ 0.004), and preoperative NGAL (regression coefficient ¼ 0.03, standard error ¼ 0.009, p ¼ 0.004), with regression coefficient ¼ –2.59, standard error ¼ 1.27, p ¼ 0.048 for the model intercept. The results of the multivariate model showed that the statistically significant predictors of hospital stay were NYHA (regression coefficient ¼ 5.26, standard error ¼ 0.82, p ¼ o0.001), and preoperative NGAL (regression coefficient ¼ 0.06, standard error ¼ 0.02, p ¼ 0.01). The authors found no association between baseline creatinine and eGFR and elevated preoperative uNGAL. In addition, preoperative, postoperative, and day one uNGAL values were similar at all time points in patients, whether they developed AKI or not. Neither preoperative nor postoperative NGAL value was associated with AKI, RRT, or death. Also, neither serum creatinine nor troponin T predicted length of stay in the ICU or hospital. Furthermore, there was not any relationship between preoperative estimated GFR and outcomes (eGFR and CVVH: p ¼ 0.065; eGFR and death: p ¼ 0.177; eGFR and ICU stay: p ¼ 0.3; and eGFR and hospital stay: p ¼ 0.107). DISCUSSION

In the present study, urinary NGAL as a noninvasive prognostic marker was investigated in 56 patients with right, left, or combined ventricular dysfunction undergoing high-risk cardiac surgery. The authors found that preoperative uNGAL was an independent predictor of length of stay in ICU and hospital, but not of AKI or RRT. There also was no association among baseline creatinine and eGFR and preoperative uNGAL. In addition, neither serum creatinine and eGFR nor troponin T predicted length of ICU or hospital stay or AKI and RRT. Serum creatinine is the standard measure for renal function but identifies renal dysfunction only when 50% of kidney function already has been lost.3,20 Furthermore, in cardiac

325

NAGL AND OUTCOME IN HEART FAILURE PATIENTS

Table 1. Demographic and Clinical Characteristics of Study Patients (n ¼ 56) Demographic data

Age, years (mean [SD]) Male sex, n (%) Weight, kg (mean [SD]) Serum creatinine, mg/dL (mean [SD]) e-glomerular filtration rate (mean [SD]) Ejection fraction (mean [SD]) Ejection fraction o45%, n (%) Logistic EuroScore, median (IQR) New York Heart Association class I, n (%) II, n (%) III, n (%) IV, n (%) Comorbidities Diabetes mellitus, n (%) Preoperative chronic renal failure, n (%) Reoperation, n (%) Surgical interventions Single-valve surgery, n (%) Multiple-valve surgery, n (%) Coronary artery bypass graft, n (%) Coronary artery bypass graft + valve, n (%) Left ventricular assist device, n (%) Other/Combined surgery, n (%) Aortic cross-clamp time, minutes Cardiopulmonary bypass time, minutes Cardiac support and troponin Need of inotropic agents, n (%) Intra-aortic balloon pump, n (%) Extracorporeal membrane oxygenation, n (%) Peak serum troponin T (ng/mL), median (IQR) Renal outcomes Peak serum creatinine (mg/dL), mean (SD) Acute kidney injury, n (%) “Risk” of RIFLE, n (%) “Injury” of RIFLE, n (%) “Failure” of RIFLE, n (%) Renal replacement therapy, n (%) Intensive care unit and hospital stay Intensive care unit stay (days), median (IQR) Prolonged intensive care unit stay (43 days) Length of hospital stay (days), median (IQR) In-hospital death, n (%) uNGAL values (ng/mL), median value (IQR) Preoperatively (T0) At intensive care unit stay arrival (T1) 24 hours postoperatively

69 ⫾ 10 31 (55.4%) 71 ⫾ 14.7 1.0 ⫾ 0.48 78.6 ⫾ 43.89 49 ⫾ 14.3 22 (39.2%) 7.9 (4.1-15.25) 3 21 31 1

(5.4%) (37.5%) (55.4%) (1.8%)

8 (14.3%) 7 (12.5%) 21 (37.5%) 22 (39.3%) 21 (37.5%) 3 (5.4%) 3 (5.4%) 4 (7.1%) 3 (5.4%) 64.0 ⫾ 27.85 94.6 ⫾ 32.84 56 20 2 1.05

(100%) (36%) (3.6%) (0.605-1.585)

1.6 ⫾ 0.80 29 (51.8%) 16 (51.8%) 9 (23%) 4 (7.1%) 3 (5.4%) 3 27 10.5 6

(2-5.25) (48.2%) (7-21.25) (10.7%)

10 (6-21) 16 (4.5-73.5) 13 (9-4)

surgery patients who develop AKI, serum creatinine level peaks approximately two days after surgery.21 NGAL is one of the most upregulated genes in the kidney soon after ischemic injury, and it fulfills many characteristics for an ideal biomarker of AKI. From the perspective of cardiorenal interaction, NGAL mainly has been studied in general cardiac surgery patients, and several studies suggest that NGAL is an early predictor of AKI.3–5,9–11 Although NGAL has been reported to be a marker of AKI, the relationship between NGAL and the current markers of renal function remains uncertain; in a study of 144 patients with a

primary diagnosis of acute decompensated heart failure, preoperative uNGAL was not associated with preoperative renal function.21 Moreover, in 1,393 older adults, the correlation between NGAL and creatinine clearance was quite modest.15 Some studies have identified NGAL as a prognostic predictor.12 Haase et al found that NGAL and cystatin C correlated with and were independent predictors of AKI duration and severity and length of stay in the ICU.13 In a multicenter analysis, patients with high levels of NGAL, measured at least 24 to 48 hours before the diagnosis of AKI, and normal levels of blood creatinine had greater risk of AKI and CVVH, longer ICU stay, longer in-hospital length of stay, and greater risk of death compared with control subject.12 The Rancho Bernardo Study found that high levels of plasma NGAL are associated independently with an increased risk of cardiovascular death.15 Wagener et al5 and Haase et al13 showed similar preoperative NGAL levels in

Table 2. Univariate Predictors of Intensive Care Unit Stay and Length of Hospital Stay

Variables

Preoperative data Age Sex Weight Diabetes Preoperative serum creatinine Preoperative ejection fraction, % Ejection fraction o45, % Reoperation Neutrophil gelatinase-associated lipocalin Preoperative glomerular filtration rate, mL/min New York Heart Association class Logistic EuroSCORE, % Preoperative intra-aortic balloon pump Intraoperative data Aortic cross-clamp time Cardiopulmonary bypass time Intraoperative intra-aortic balloon pump Intensive care unit arrival Neutrophil gelatinase-associated lipocalin T1 Serum creatinine T1 Troponin T1 Intensive care unit data Postoperative intra-aortic balloon pump Troponin T2 Troponin 24 hours Peak serum troponin Serum creatinine 24 hours Peak serum creatinine Neutrophil gelatinase-associated lipocalin 24 hours Acute kidney injury Renal replacement therapy

LOS (p Value)

0.6 0.9 0.6 0.7 0.09 0.2 0.04 0.7 0.03 0.11 0.006 0.049 0.13

ICU stay (p Value)

0.6 0.009 0.8 0.051 0.7 0.4 0.5 0.015 0.04 0.3 0.008 o0.001 0.5

0.3 0.8 0.5

0.3 0.5 0.5

0.02

0.4

0.048 0.7

0.4 0.5

0.3 0.9 0.8 0.8 0.15 0.16 0.3

o0.001 0.3 0.3 0.3 0.6 0.6 0.3

0.5 0.5

0.007 0.001

NOTE: The best multivariate model was selected by stepwise selection method of univariate significant covariates (univariate p value o0.2) and was reported in the text. Abbreviations: ICU, intensive care unit; LOS, length of stay.

326

SILVETTI ET AL

patients who later developed AKI compared with patients without postoperative AKI. In this study, for the first time, a high preoperative uNGAL value was associated with length of stay in the ICU and hospital in a unique group of patients with right-sided and/or left-sided myocardial dysfunction undergoing high-risk cardiac surgery. In particular, preoperative uNGAL added complementary information to established risk factors. In a previous study,14 this association was not identified, probably because patients were at a lower risk than the present population, were more heterogenous, and the population was smaller. Although NGAL is known by many as a marker of acute renal injury, the results suggest that preoperative uNGAL could provide other prognostic information and is not merely a surrogate measure of renal function or risk. In particular, no association between baseline creatinine and eGFR and elevated preoperative uNGAL levels were found. The concentration of NGAL in high-risk patients may depend on other conditions: NGAL is secreted by renal tubular cells, leucocytes, and several other types of epithelial cells, and synthesis is upregulated markedly in tissue injury, inflammation, and cancer.22,23 Thus, in this cohort, uNGAL values may have reflected a state of otherwise undetected increased inflammation, which then was reflected by a longer duration of ICU and hospital stay. Of clinical importance, uNGAL was the only biomarker predicting prolonged ICU and hospital stay. Neither serum creatinine nor serum troponin T was a significant predictor of length of stay at multivariate analysis. The major limitation of this study was the relatively small number of patients. Being a small cohort study, the results

should be confirmed in a large population before including preoperative uNGAL among the established predictors of prolonged ICU stay and LOS. Furthermore, the population was heterogenous for baseline characteristics and type of intervention. This study could have been underpowered to detect a difference in AKI in a heterogenous adult cardiac surgery population. The lack of relationship between NGAL and renal dysfunction may be due to a type-II error. However, the lack of a trend toward predictive value argues against this as a single explanation. Another limitation of this study was that the authors investigated only urinary NGAL, as most authors believe that urinary NGAL generally is more reflective of NGAL from a urinary origin (in contrast to serum NGAL). Finally, other novel markers of AKI, such as the IL-18 that Parikh et al suggested in their study,24 were not analyzed in this manuscript.

CONCLUSIONS

The results of this study showed that, in adult high-risk cardiac surgery patients, the preoperative value of NGAL is an independent predictor of prolonged ICU and hospital stay. An early predictive marker for ICU and hospital stay may increase awareness of patients being at increased risk of developing adverse events. This may lead to a greater justification for, and a greater effort to intensify monitoring so that the patients identified by these biomarkers can receive more prolonged invasive hemodynamic monitoring and greater measures to optimize organ function.

REFERENCES 1. Coppolino G, Presta P, Saturno L, et al: Acute kidney injury in patients undergoing cardiac surgery. J Nephrol 26:32-40, 2013 2. Chertow GM, Levy EM, Hammermeister KE, et al: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104:343-348, 1998 3. Tuladhar SM, Püntmann VO, Soni M, et al: Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol 53: 261-266, 2009 4. Wagener G, Jan M, Kim M, et al: Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105:485-491, 2006 5. Wagener G, Gubitosa G, Wang S, et al: Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 52:425-433, 2008 6. Bolignano D, Donato V, Coppolino G, et al: Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 52:595-605, 2008 7. Cruz DN, de Cal M, Garzotto F, et al: Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 36:444-451, 2010 8. Haase-Fielitz A, Bellomo R, Devarajan P, et al: Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—A prospective cohort study. Crit Care Med 37: 553-560, 2009 9. Mishra J, Dent C, Tarabishi R, et al: Neutrophil gelatinaseassociated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231-1238, 2005

10. Bennett M, Dent CL, Ma Q, et al: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study. Clin J Am Soc Nephrol 3:665-673, 2008 11. Mishra J, Ma Q, Prada A, et al: Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534-2543, 2003 12. Haase M, Devarajan P, Haase-Fielitz A, et al: The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: A multicenter pooled analysis of prospective studies. J Am Coll Cardiol 57:1752-1761, 2011 13. Haase M, Bellomo R, Devarajan P, et al: Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg 88:124-130, 2009 14. Bignami E, Frati E, Ceriotti F, et al: Urinary neutrophil gelatinase-associated lipocalin as an early predictor of prolonged intensive care unit stay after cardiac surgery. Ann Card Anaesth 15: 13-17, 2012 15. Daniels LB, Barrett-Connor E, Clopton P, et al: Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study. J Am Coll Cardiol 59: 1101-1109, 2012 16. Eriksen BO, Hoff KR, Solberg S: Prediction of acute renal failure after cardiac surgery: Retrospective cross‐validation of a clinical algorithm. Nephrol Dial Transplant 18:77-81, 2003 17. Nashef SA, Roques F, Michel P, et al: European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 16:9-13, 1999

NAGL AND OUTCOME IN HEART FAILURE PATIENTS

18. Wernovsky G, Wypij D, Jonas RA, et al: Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226-2235, 1995 19. Bellomo R, Ronco C, Kellum JA, et al: Acute renal failure— Definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204-R212, 2004 20. Sachin SS, et al: Early diagnosis of acute kidney injury: The promise of novel biomarkers. Blood Purif 28:165-174, 2009

327

21. Dupont M, Shrestha K, Singh D, et al: Lack of significant renal tubular injury despite acute kidney injury in acute decompensated heart failure. Eur J Heart Fail 14:597-604, 2012 22. Mishra J, Mori K, Ma Q, et al: Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 15:3073-3082, 2004 23. Devarajan P: Neutrophil gelatinase-associated lipocalin: New paths for an old shuttle. Cancer Ther 5:463-470, 2007 24. Parikh CR, Coca SG, Thiessen-Philbrook H, et al: Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol 22:1748-1757, 2011

Preoperative urinary neutrophil gelatinase-associated lipocalin and outcome in high-risk heart failure patients undergoing cardiac surgery.

To investigate the ability of early urinary neutrophil gelatinase-associated lipocalin to predict postoperative complications in adult patients with v...
123KB Sizes 0 Downloads 0 Views