The dose-related effects of dexmedetomidine on renal functions and serum neutrophil gelatinase-associated lipocalin values after coronary artery bypass grafting: a randomized, triple-blind, placebo-controlled study.
Acute kidney failure after coronary artery bypass grafting (CABG) is a serious complication that increases morbidity and mortality rates. Early detection and prevention of this complication are very important. A novel biomarker named neutrophil gelatinase-associated lipocalin (NGAL) can play an important role in early diagnosis of acute kidney injury. Recent studies on the favourable effects of Dexmedetomidine on cardiac surgery have been published. The aim of this study is to investigate whether there is a dose-dependent positive effect of Dexmedetomidine on neutrophil gelatinase-associated lipocalin levels and renal functions when used after CABG.
Our randomized, triple-blinded, placebo-controlled study was conducted among 295 patients scheduled for CABG surgery between August 2009 and March 2011 in a tertiary cardiac and vascular surgery clinic. A total of 90 consecutive patients who met inclusion criteria were randomized and divided into three groups. The first group received a placebo. The second and the third groups received 4 and 8 µg/cc concentration of the Dexmedetomidine infusion, respectively. Infusion rates were regulated to obtain sedation with a Ramsey sedation score of 2 or 3. Patients were regrouped according to the total Dexmedetomidine dose. Statistical analyses of variables including serum neutrophil gelatinase-associated lipocalin values and conventional renal function tests were made for all six possibilities before the blind was broken.
Results of conventional renal function tests were not significantly different. However, neutrophil gelatinase-associated lipocalin levels for the first postoperative day for placebo, low-dose and high-dose Dexmedetomidine groups were 176.8 ± 145.9, 97.7 ± 63.4 and 67.3 ± 10.9 ng/ml, respectively. These values were significantly different among the groups (P <0.001).
In our study, we found that Dexmedetomidine infusion for sedation after CABG under cardiopulmonary bypass can be useful in the prevention of kidney injury. Conventional renal function tests, including blood urea nitrogen, serum creatinine, urine output and creatinine clearance rate measurements typically may not detect the development of acute kidney dysfunction in the first 48-h postoperative period. Differences were detected in renal function in the early postoperative period and the development of acute kidney injury, as determined by measurements of blood NGAL levels, was significant and dose-dependent.
Balkanay OO
，Goksedef D
，Omeroglu SN
，Ipek G
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Neutrophil gelatinase associated lipocalin as a biomarker for acute kidney injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.
Acute kidney injury (AKI) is a significant cause of morbidity and mortality following cardiac surgery throughout the world. The paucity of early biomarkers has hampered early therapeutic intervention. Our aim was to evaluate plasma neutrophil gelatinase associated lipocalin (NGAL) levels as a predictor of renal injury in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) along with markers of oxidative stress.
About 30 patients undergoing CABG with CPB were prospectively studied. Blood was collected before bypass, at 4, 12, and 24 hr after CPB initiation, for the analysis of NGAL and oxidative stress markers.
Eight of 30 patients (26.6%) developed AKI, while 22 (73.4%) did not, as measured by serum creatinine, after 48-72 hr of surgery. However, plasma NGAL levels at 4 hr were high in patients who developed AKI compared with those who did not (352.97 +/- 49.32 vs. 199.83 +/- 23.28 ng/mL, p = 0.000). There was a significant difference in aortic cross-clamp time (p = 0.000), duration of CPB (p = 0.000), and ventilation duration (p < 0.05) between the two groups. The level of malondialdehyde (MDA), a marker of oxidative stress, was higher only at 4 hr in the AKI group. No significant differences were observed in the level of antioxidants between the two groups. A significant correlation was found between plasma NGAL at 4 hr and the change in serum creatinine (r = 0.863, p = 0.006) as well as ventilation duration (r = 0.830, p = 0.011). The sensitivity and specificity of plasma NGAL at 4 hr after CPB was optimal at the 229 ng/mL cut-off with an area under the curve of 0.98 for prediction of AKI.
Measurement of plasma NGAL in patients in the first few hours after CPB is predictive of AKI. Oxidative stress as measured by the level of MDA and antioxidants has no substantial role in the progression of AKI during CABG with CPB.
Prabhu A
，Sujatha DI
，Ninan B
，Vijayalakshmi MA
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Comparison of Neutrophil Gelatinase-Associated Lipocalin Versus B-Type Natriuretic Peptide and Cystatin C to Predict Early Acute Kidney Injury and Outcome in Patients With Acute Heart Failure.
Neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF) as marker of tubular damage and renal dysfunction; however, less data are available in patients with acute HF. Because of high rate of acute kidney injury (AKI) development, we aimed to investigate the role of NGAL in predicting early AKI development; second, we compared NGAL with respect to cystatin C, B-type natriuretic peptide (BNP), renal function, and blood urea nitrogen (BUN) for outcome prediction. We measured admission serum NGAL, cystatin C, and BNP in 231 patients affected to acute HF; all patients were submitted to daily creatinine, estimated glomerular filtration rate, and measurement to identify inhospital AKI defined by Risk, Injury, Failure, Loss, End-Stage Kidney Disease and Acute Kidney Injury Network criteria. We also measured admission and discharge estimated glomerular filtration rate, creatinine, and BUN to evaluate their prognostic role during a 6-month follow-up period; 78 patients developed AKI during hospitalization. In these subjects, NGAL levels were significantly increased respect to patients without AKI (295 ± 228 vs 129 ± 108 ng/ml, p <0.001). A cutoff of 134 ng/ml has been related to AKI with good sensibility and specificity (85% and 80%, respectively; area under the curve 0.81, p <0.001). BNP was also mildly increased (1,000 ± 906 vs 746 ± 580 pg/ml, p = 0.03) but not cystatin C. Patients with chronic kidney disease demonstrated higher NGAL levels compared with subjects with preserved renal function (258 ± 249 and 120 ± 77 ng/ml, p <0.001). The receiver-operating characteristic curve analysis demonstrated that increased NGAL values were associated with increased mortality (cutoff 170 ng/ml, sensibility 60%, specificity 82%, accuracy 71%, area under the curve 0.77, p <0.001). The same significant correlation was also found for BUN at discharge (cutoff 100 mg/dl, sensibility 65%, specificity 85%, accuracy 71%, area under the curve 0.77, p <0.001). Multivariable Cox regression analysis showed that cutoff 170 ng/ml was related with adverse outcome (hazard ratio 1.77, confidence interval 1.24 to 2.83, p = 0.01). In conclusion, NGAL measurement is a sensible tool to predict AKI during hospitalization. Elevated NGAL levels appear to be related to BUN increase and post-discharge outcome. This suggests a prognostic role of tubular damage beyond renal dysfunction.
Palazzuoli A
，Ruocco G
，Pellegrini M
，De Gori C
，Del Castillo G
，Franci B
，Nuti R
，Ronco C
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Serum Cystatin C as an Early Marker of Neutrophil Gelatinase-associated Lipocalin-positive Acute Kidney Injury Resulting from Cardiopulmonary Bypass in Infants with Congenital Heart Disease.
Acute kidney injury (AKI) is a common complication resulting from cardiopulmonary bypass in infants. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive and specific marker of such injury. In this study, we compared the performance of serum cystatin C (Cys C) and serum creatinine (Cr) as early markers of renal dysfunction in infants undergoing cardiac surgery under bypass.
The study was designed as a prospective observational study. The study was conducted in the cardiac intensive care unit (ICU) of a tertiary, academic children's hospital in the United States. Infants (age <1 year) undergoing cardiac surgery under cardiopulmonary bypass were included in the study.
Acute kidney injury was defined based on postoperative urinary NGAL.
A total of 17 infants were included in the study, and five of them developed AKI. Serum Cys C and Cr levels were measured postoperatively on days 1, 2, and 3, and compared with baseline levels. On postoperative day 2, infants with AKI showed significant change from baseline in serum Cys C levels compared with non-AKI infants (28% vs. -9%, P = .03). The two groups did not show significant differences with respect to rise in serum Cr on any of the 3 postoperative days. Serum Cr on days 1 and 2 showed nonspecific increases in both AKI and non-AKI groups. The area under the receiver operating characteristic curve for day 2 Cys C was 0.87 (95% CI 0.67-1.00) in recognizing NGAL-positive AKI.
Postoperative serum Cys C appears to be a more specific and sensitive biomarker for NGAL-positive AKI resulting from cardiopulmonary bypass surgery in infants undergoing cardiac surgery.
Herbert C
，Patel M
，Nugent A
，Dimas VV
，Guleserian KJ
，Quigley R
，Modem V
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