Abstract
Purpose
Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker of acute kidney injury (AKI). Goal-directed therapy (GDT) in on-pump coronary artery bypass grafting (CABG) has been associated with lower post-operative NGAL levels in recent studies. The present study aimed at comparing plasma (P) and urinary (U)-NGAL levels following the use of GDT versus conventional haemodynamic therapy (CT) in patients undergoing on-pump CABG.
Methods
A prospective randomised controlled study conducted in a single university hospital. A total of 54 patients in the GDT group and 56 patients in CT group after exclusions.
Results
U-NGAL was significantly lower immediately post-surgery (T1) in GDT group (25.11 ± 1.5 versus 27.80 ± 1.7 μg/L; p < 0.001) and at 4 h (T2) (38.19 ± 23.6 versus 52.30 ± 28.3 μg/L; p = 0.006) and at 24 h post-operatively (T3) (34.85 ± 14 versus 39.7 ± 11.1 μg/L; p = 0.047). P-NGAL was comparable between groups at T1 but lower in the GDT group at T2 (92.81 ± 4.8 versus 94.77 ± 4.5 μg/L; p = 0.03) and T3 (67.44 ± 3.7 versus 75.96 ± 5.3 μg/L; p < 0.001). U-NGAL levels correlated well with the peak post-operative creatinine as compared to P-NGAL. On-pump patients manifest neutrophil activation, accounting for comparable levels of P-NGAL in the two groups at T1. GDT-based haemodynamic management resulted in lower U-NGAL levels at T1, T2 and T3 and lower P-NGAL levels at T2 and T3.
Conclusions
Haemodynamic optimisation with GDT prevents further renal insult initiated with the inflammatory activation with cardiopulmonary bypass (CPB), as evidenced by lower post-operative U-NGAL levels.
Keywords: Acute kidney injury, Cardiopulmonary bypass, Goal-directed therapy
Introduction
AKI is a potential complication of cardiac surgery and contributes significantly to post-operative morbidity and mortality [1–3]. Cardiopulmonary bypass (CPB) has been specifically implicated as trigger of inflammatory cascade activation and renal injury [4]. In addition to the inflammation related to CPB, various other factors contributing to renal tubular injury place the cardiac surgical patients at an elevated risk of developing post-operative AKI. There is an increased emphasis on the management aimed at minimising the initial renal insult inflicted as a result of extracorporeal circulation with haemodynamic optimisation of the renal perfusion.
GDT is a term encompassing the use of cardiac output or similar parameters to guide intravenous fluid and inotropic therapy [5]. It involves goal-directed manipulation of cardiac preload, afterload, contractility to achieve a balance between systemic oxygen demand and delivery. The maintenance of this tenuous balance in favour of an improved end-organ perfusion forms the basis of an encouraging literature on the positive role of GDT in decreasing morbidity in cardiac surgical patients [6, 7]. Recent studies have also demonstrated an improved biomarker profile following the haemodynamic management with GDT in on-pump CABG [8].
Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa iron-transporting glycoprotein which accumulates in the kidney tubules and urine as a result of nephrotoxic and ischaemic insults. Various studies have proposed NGAL as an early, sensitive, non-invasive biomarker to diagnose AKI [9–12]. P-NGAL is a biomarker of both inflammation and renal tubular injury [13]. However, U-NGAL is a more specific biomarker of tubular injury than plasma NGAL [14]. Therefore, measuring both plasma and urine NGAL in patients receiving GDT in comparison to the CT may help study the role of GDT in attenuating the further progression of initial renal insult from CPB. The primary study outcome measure was the P-NGAL and U-NGAL levels post-operatively and at 4 h and 24 h after surgery. The peak post-operative plasma creatinine, development of AKI and requirement of renal replacement therapy (RRT) constituted the secondary outcomes of comparison between the two groups.
Materials and methods
This was a prospective randomised controlled study, conducted at our tertiary care hospital, after obtaining ethical clearance from the institutional review board and informed consent. One hundred twenty patients of 18–85 years of age, scheduled for elective CABG necessitating the use of CPB, were randomly divided into the GDT and CT group by a sealed envelope technique. Patients with cardiac dysrhythmias and contraindication to the central venous cannulation were excluded. The subjects requiring the initiation of intra-aortic balloon pump (IABP) and arrhythmias were excluded because the FloTrac™ is not equipped to identify the waveforms of arterial pressure waveform while using IABP and it is not accurate in presence of arrhythmias.
The exclusion criteria which were common to both the groups were:
Pre-operative haematocrit < 25%
Leukocyte-rich blood transfusion < 30 days before surgery
Coronary angiography within 48 h before surgery
Preexisting AKI
Pre-operative RRT
Chronic kidney disease stage 5
Postrenal transplant
Cardiogenic shock prior to surgery
Infective endocarditis
Recent Myocardial infarction within last month
Pre-operative IABP support
Emergency surgery
All patients received intramuscular premedication of morphine 0.1 mg/kg and promethazine 0.5 mg/kg, 30 min before the procedure. The anaesthesia was induced and maintained as per institutional protocols. All the patients were ventilated with 50% oxygen in air using 1 MAC sevoflurane and respiratory rate adjusted to maintain ETCO2 35–45 mm of Hg. In both the groups, patients were continuously monitored by ECG, pulse oximetry, end tidal CO2, invasive arterial blood pressure, nasopharyngeal temperature and urine output. The blood glucose level was maintained in between 80 and 180 mg/dL.
The surgical approach in all patients was by median sternotomy. The CPB circuit consisted of a standardised roller pump, tubing, a membrane oxygenator (Affinity Trillium Coated Oxygenator, Medtronic, Minneapolis, MN) and an arterial filter. The pump prime solution comprised of 2 L of crystalloid solution (Ringer lactate, Baxter, Sydney, Australia). CPB was managed with a pump flow of 2.4 L/min/m2 and mild hypothermia (33–35 °C). Acid–base management involved the alpha stat method (with no correction for temperature). Haemofiltration was performed in both the groups to maintain haematocrit > 30% and potassium in a normal range (3.5–4.5 mEq/L) before coming off CPB.
Myocardial protection during aortic cross clamping was with antegrade cardioplegia, and all proximal graft anastomoses were performed during the period of complete aortic clamping.
In the GDT group, the Cardiac Index (CI) using Flotrac software version 3/volume view set (Edwards Lifesciences Corp., One Edwards Way Irvine, CA 92614) and the central venous oxygen saturation using Pre Sep catheter (Edwards Lifesciences Corp., One Edwards Way Irvine, CA 92614) were monitored. A Volume View™ cardiac output monitoring sensor was connected to the radial arterial cannula in the GDT group. A Pre Sep™ catheter (continuous central venous oximetry) was inserted through right internal jugular vein in the GDT group. Pressure transducers and presep oximetry catheters were used to transfer these signals from patients to its data box. An algorithm embedded in its data box processes signals and provides stroke volume (SV), CO, Cardiac Index, systemic vascular resistance (SVR), stroke volume variation (SVV) and oxygen delivery index (DO2I). The haemodynamic goals were as follows: GDT group—the goals were to maintain MAP > 90 mmHg, central venous pressure (CVP) > 6–8 mmHg, urine output > 0.5 ml/kg/h, SpO2 > 95%, haematocrit > 30, ScVO2 > 70%, CI > 2.5 L/min/m2, SVV < 10%, SVRI > 1500–2500, dynes/s/cm5/m2, DO2I > 450–600 ml/min/m2 and stroke volume index > 30–65 ml/beat/m2.
Conventional therapy group—the haemodynamic goals were to maintain MAP > 90 mmHg, CVP > 6–8 mmHg, urine output > 0.5 ml/kg/h, SpO2 > 95% and haematocrit > 30.
After surgery, all the patients were transferred to ICU on mechanical ventilation. The patients were gradually weaned in the ICU. Once they met criteria of extubation, the endotracheal tube was removed from the trachea. The decision was based on the normalisation of arterial blood gas (ABG) analysis of pH 7.35–7.45, PaO2 more than 100 mm of Hg (with FiO2 of less than 50%), and lactate less than 2 mmol/L. Thereafter, patients were monitored for the next 24 h, and any derangement was corrected at the earliest. No nephrotoxic drugs were administered in the peri-operative course of management.
All patients received maintenance fluid ringer lactate 1 ml/kg/h. Haematocrit was maintained more than 30% and PRBC was administered as required. The CVP was maintained at 6–8 mm of Hg. In scenario of a reduced CVP, fluid bolus of 100 ml crystalloid or colloid was administered. The mean arterial pressure (MAP) was optimised to remain greater than 90 mm of Hg, with the titration of fluid boluses and inotrope infusion of dobutamine starting from 5 μg/kg/min, epinephrine with starting dose of 0.05 μg/kg/min or norepinephrine with starting dose of 0.05 μg/kg/min and vasodilator infusion of NTG of 0.5 μg/kg/min. The dose of inotrope infusions was escalated if required. ABG was done at 4 hourly intervals. The hourly urine output was monitored and maintained at values greater than 0.5 ml/kg/h in both the groups.
In addition, following interventions were done to manage the patients in GDT group. An increase in SVV more than 10% was managed by giving fluid boluses, which was repeated at frequent intervals to maintain SVV less than 10%. With low haematocrit and ScVO2 reading of less than 70%, transfusion of packed red blood cell was given to keep haematocrit more than 30%. With persistent low ScVO2 along with low CI, inotropic support of dobutamine starting from 5 μg/kg/min or epinephrine with starting dose of 0.05 μg/kg/min was initiated. The inotropic support was titrated to maintain CI within 2.0–4.5 L/min/m2. These haemodynamic parameters were continuously monitored for 24 h in the ICU and corrected according to protocol. Each patient was followed for 1 month or until death.
The venous blood samples were collected on the day of admission for the pre-operative creatinine estimation. The blood samples for NGAL estimation were drawn from the arterial line and urine was collected for the measurement of biochemistry before the initiation of surgery (T0), on arrival in the ICU (T1), 4 h (T2) and at 24 h (T3). The arterial blood samples were collected in EDTA vials and stored at four degrees centigrade (4 °C) and were immediately sent for centrifugation followed by the biomarker measurement by the ELISA method.
The plasma creatinine was followed daily with the highest value during hospital admission being recorded as the peak post-operative creatinine. The diagnostic criteria for defining AKI was taken from acute kidney injury network (AKIN/RIFLE) criteria, i.e. an AKI with a rapid time course (< 48 h), reduction of kidney function with an absolute increase in serum creatinine of ≥ 0.3 mg/dl (≥ 26.4 μmol/L) or a percentage increase in serum creatinine of ≥ 50% and a reduction in urine output, defined as < 0.5 ml/kg/h for more than 6 h.
The quantitative variables were expressed as mean and standard deviation and compared between groups using unpaired t test and within groups across follow-ups using paired t test. The qualitative variables were expressed as frequencies/percentages and compared between groups using chi-square/Fisher’s exact test. To measure the correlation between variables, Pearson’s correlation or Spearman’s rank correlation was used as required. A p value < 0.05 was considered as statistically significant. SPSS version 16.0 (IBM, SPSS Statistics, Chicago, SPSS Inc.) software was used for statistical analysis.
Results
A total of 120 patients enrolled in the study, out of which 64 patients were allocated to the GDT group and 56 patients to the CT group in a randomised fashion. Ten patients were excluded from the GDT group in view of refractory arrhythmias and IABP support (Fig. 1). The data of remaining 54 patients in the GDT group and 56 patients in the CT group was analysed. The demographic data, comorbidity profile, European system for cardiac operative risk evaluation (EuRO Score), duration of CPB, duration of aortic cross clamping (AOXCL) and average number of grafts were comparable between the two groups (Table 1). The two groups were comparable with respect to the risk factors for the development of post-operative AKI and net fluid balance (Table 2).
Fig. 1.
The study design depicting the enrolment, allocation and exclusion of the patients in the two groups
Table 1.
The haemodynamic goals of management in the GDT and conventional therapy groups. (A) Conventional haemodynamic goals, (B) PreSep™ oximetry and (C) advanced haemodynamic goals. SpO2, oxygen saturation of the arterial blood
| GDT | Conventional therapy |
|---|---|
|
(A) MAP > 90 mmHg CVP > 6–8 mmHg Urine output > 0.5 ml/kg/h SpO2 > 95% Haematocrit > 30 (B) ScVO2 > 70% (C) CI > 2.5 L/min/m2 SVV < 10% SVRI > 1500–2500 dynes/s/cm5/m2 DO2I > 450–600 ml/min/m2 Stroke volume index > 30–65 ml/beat/m2 |
MAP > 90 mmHg CVP > 6–8 mmHg Urine output > 0.5 ml/kg/h SpO2 > 95% Haematocrit > 30 |
Table 2.
Characteristics (demographics and comorbidities) in the two groups
| Parameter | GDT group (n = 54) | CT group (n = 56) | p value |
|---|---|---|---|
| Age (years) | 55.46 ± 13.18* | 55.14 ± 12.96* | 0.898 |
| Male:female | 39:15 | 42:14 | 0.370 |
| BMI (kg/m2) | 25.88 ± 2.36* | 25.79 ± 2.64* | 0.857 |
| Diabetes mellitus | 7 (12.96%) | 10 (17.86%) | 0.239 |
| Hypertension | 17 (31.48%) | 21 (37.5%) | 0.253 |
| Peripheral vascular disease | 3 (5.56%) | 2 (3.57%) | 0.309 |
| Euro SCORE | 3.11 ± 0.79* | 3.21 ± 0.97* | 0.543 |
| LVEF | 45.93 ± 15.85* | 46.16 ± 15.67* | 0.938 |
| Baseline creatinine (μmol/L) | 77.39 ± 7.79* | 76.68 ± 8.4* | 0.647 |
| NYHA I, II, III | 4:44:6 | 2:47:7 | 0.19, 0.37, 0.41 |
| Previous myocardial infarction | 16 (29.63%) | 18 (32.14%) | 0.388 |
| PRBC:FFP:PC | 2.72 ± 1.4:3.37 ± 1.2:2.78 ± 0.7 | 2.77 ± 1.4:3.11 ± 1.1:2.98 ± 0.7 | 0.86, 0.23, 0.13 |
| Grafts | 3.98 ± 0.86* | 3.88 ± 0.76* | 0.493 |
| CPB time (min) | 96.44 ± 4.92* | 96.43 ± 5.11* | 0.987 |
| AOXCL time (min) | 54.33 ± 3.55* | 54.57 ± 3.67* | 0.730 |
| Average extra volume | 583.22 ± 97.49 | 603.91 ± 98.51 | 0.270 |
| Used (ml) | |||
| Haemofiltered volume (ml) | 739.9 ± 79.16 | 741.73 ± 72.82 | 0.904 |
(*Standard deviation, p value < 0.05 is considered significant)
The haematocrit, urine output, oxygen saturation of arterial blood (SpO2), MAP and CVP were maintained within the physiological limits in both the groups. The additional advanced haemodynamic parameters such as the ScVO2, CI, SVV, SVRI, SVI and DO2I were monitored and optimised in the GDT group. The GDT and CT group were comparable in regard to the post-operative outcome (peak post-operative creatinine, RRT, sepsis, AKI, ICU stay, duration of inotropes and mortality) except the duration of post-operative ventilation which was significantly lower in the GDT group (Table 3).
Table 3.
Post-operative outcomes in the two groups
| Parameter | GDT group (n = 54) | CT group (n = 56) | p value |
|---|---|---|---|
| Inotropes/vasopressors due to LCOS/low SVR | |||
| 4 h post-operatively | 24 (44.44%) | 26 (46.43%) | 0.417 |
| 24 h post-operatively | 7 (12.96%) | 8 (14.29%) | 0.420 |
| Sepsis | 3 (5.56%) | 4 (7.14%) | 0.367 |
| AKI | 3 (5.56%) | 4 (7.14%) | 0.367 |
| RRT | 2 (3.70%) | 3 (5.36%) | 0.339 |
| Peak creatinine (μmol/L) | 109.65 ± 16.97* | 114.25 ± 19.65* | 0.192 |
| ICU-LOS (h) | 28.5 ± 4.87* | 28.71 ± 4.6* | 0.813 |
| Inotropes duration (h) | 10.98 ± 6.69* | 10.93 ± 7.81* | 0.970 |
| Ventilation duration (min) | 364.93 ± 11.18* | 371.09 ± 18.87* | 0.040 |
| IABP support | Excluded | 4 (7.14%) | – |
| Mortality | 2 (3.70%) | 3 (5.36%) | 0.339 |
(*Standard deviation, p value < 0.05 is considered significant)
The P-NGAL and U-NGAL profiles were considerably different when compared between the groups. The P-NGAL and the U-NGAL were comparable at T0 which served as a baseline for comparison. The post-operative U-NGAL levels were considerably lower in the GDT group when compared to the CT group at T1, T2 and T3 (Table 4). In contrast to the U-NGAL, the P-NGAL levels were comparable at T1 but decreased to a higher degree in the GDT group with time to result in lower levels compared to the CT at T2 and T3 (Table 4). Fig. 2 depicts that P-NGAL levels comparably peak at T1 in both the groups and settle down in both the groups. However, the U-NGAL levels peak at T2 in the two groups and drop at T3 (Fig. 2).
Table 4.
Post-operative NGAL profile in the two groups
| Parameter | Time | GDT group (n = 54) | CT group (n = 56) | p value |
|---|---|---|---|---|
| P-NGAL (μg/L) | T 0 | 49.13 ± 3.61* | 48.25 ± 2.65* | 0.147 |
| T 1 | 122.50 ± 6.29* | 124.54 ± 6.54* | 0.099 | |
| T 2 | 92.81 ± 4.84* | 94.77 ± 4.47* | 0.030 | |
| T 3 | 67.44 ± 3.75* | 75.96 ± 5.28* | < 0.001 | |
| U-NGAL (μg/L) | T 0 | 11.96 ± 1.37* | 11.91 ± 1.35* | 0.841 |
| T 1 | 25.11 ± 1.53* | 27.80 ± 1.7* | < 0.001 | |
| T 2 | 38.19 ± 23.64* | 52.30 ± 28.33* | 0.006 | |
| T 3 | 34.85 ± 13.99* | 39.70 ± 11.15* | 0.047 |
(*Standard deviation, p value < 0.05 is considered significant). T0 (baseline), T1 (post-operative), T2 (4 h post-operatively), T3 (24 h post-operatively)
Fig. 2.
The trend plot analysis depicting the levels of mean P-NGAL (upper panel) and U-NGAL (lower panel) in micrograms per litre at T0 (baseline), T1 (post-operative), T2 (4 h post-operatively) and T3 (24 h post-operatively) in the GDT and CT groups
Fig. 2 also demonstrates that the elevations in U-NGAL in the CT group as compared to the GDT group were distinctly higher versus the elevations in P-NGAL.
The post-operative U-NGAL levels correlated well with the peak post-operative creatinine in comparison to the post-operative P-NGAL at T2 and T3 with a comparable correlation at T1 (Table 5). A total of 7 patients developed AKI in the study which included 3 patients in the GDT and 4 patients in the CT group (Table 3). Fig. 3 plots the P-NGAL and U-NGAL levels in the patients with and without AKI, depicting the characteristic peaking with much higher elevations in the U-NGAL levels in the AKI group compared to the non-AKI group versus the elevations in P-NGAL.
Table 5.
Correlation of post-operative P-NGAL and U-NGAL with peak post-operative creatinine
| Parameter (P/U-NGAL) | Time | Correlation with peak post post-operative creatinine (r) | p value |
|---|---|---|---|
| P-NGAL (μg/L) | T 1 | 0.463 | < 0.001 |
| T 2 | 0.306 | 0.001 | |
| T 3 | 0.284 | 0.003 | |
| U-NGAL (μg/L) | T 1 | 0.444 | < 0.001 |
| T 2 | 0.856 | < 0.001 | |
| T 3 | 0.700 | < 0.001 |
(*Standard deviation, p value < 0.05 is considered significant). T0 (baseline), T1 (post-operative), T2 (4 h post-operatively), T3 (24 h post-operatively)
Fig. 3.
The trend plot analysis depicting the levels of mean P-NGAL (upper panel) and U-NGAL (lower panel) in micrograms per litre at T0 (baseline),T1 (post-operative), T2 (4 h post-operatively), T3 (24 h post-operatively) in the patients with AKI and without AKI
Discussion
Extracorporeal circulation and the associated inflammatory sequel predispose the cardiac surgical patients to an increased susceptibility to develop post-operative AKI [15]. The optimisation of the renal perfusion, supply-demand ratio by providing a favourable haemodynamic milieu obviates the need of higher vasoactive infusions and circulatory assist devices, thereby better preserving the renal function. The GDT algorithm-based fluid, inotropes and vasopressor titration for haemodynamic optimisation are largely aimed at improving the morbidity profile of the cardiac surgical patients by maintaining the end-organ perfusion. The availability of early and sensitive biomarkers aimed at predicting AKI after cardiac surgery may enable the physicians to monitor the efficacy of the interventions targeted at ameliorating the further deterioration of the underlying subtle renal insult. This largely stems from the observation that the serum creatinine has a low reliability in predicting renal injury. Moreover, the serum creatinine levels may take several hours to days to establish a steady state even in the setting of AKI in addition to being influenced by several non-renal factors.
P-NGAL is a novel biomarker of both inflammation and tubular injury combined, and urinary NGAL is a promising biomarker of post-operative in cardiac surgical patients [16, 17]. However, NGAL has been demonstrated to be a marker of neutrophil granulocyte activity [13]. Considering the potential of CPB to initiate a general inflammatory response and the various other haemodynamic factors related to tubular injury in addition to CPB, the present study was a novel study conducted to evaluate the effects of GDT on the post-operative P-NGAL and U-NGAL profile. The simultaneous measurement of both P-NGAL and U-NGAL in patients receiving GDT was aimed at studying the mechanism of GDT in attenuating the inflammatory and tubular effects of CPB.
The present study demonstrated peculiarly different post-operative P-NGAL and U-NGAL profiles. The P-NGAL levels were comparable immediately after surgery in both the groups with subsequent decline in both the groups at 4 h and 24 h post-operatively. However, the decline in the P-NGAL levels was more marked in the GDT group. In contrast to P-NGAL, the U-NGAL levels were significantly lower in the GDT group at all post-operative time frames with a characteristic peaking of the U-NGAL levels at 4 h post-operatively. The time frame of peak post-operative U-NGAL levels in the study is consistent with the findings of previous studies [18, 19].
The findings of the study can be attributed to the following points of discussion. P-NGAL being a combined marker of inflammation and tubular injury was elevated comparably in both the groups owing to the effects of CPB, with gradual settling of levels with GDT being continued for 24 h post-operatively. U-NGAL, on the other hand being a more specific marker of tubular injury, was markedly lower in the GDT group over the entire course of GDT. The finding that the mean post-operative U-NGAL levels at T2 (4 h post-operatively) in the 7 patients who developed AKI were 145.14 ± 10.96 μg/L compared to 38.59 ± 6.34 μg/L in the patients who did not develop AKI reemphasises the abovementioned fact. However, on the other hand, the mean of the peak values of post-operative P-NGAL levels in AKI patients was 132.29 ± 1.5 μg/L compared to 122.94 ± 6.25 μg/L in the rest of the patients.
The favourable impact of GDT on the post-operative NGAL profile is in agreement with a few initial studies [8]. Given the fact that the neutrophils are a potential source of P-NGAL, and CPB-induced neutrophil activation has been previously described, these findings suggest greater CPB-mediated neutrophil activation [20, 21]. Such activation is believed to be one of the predominant mechanisms of CPB-associated inflammation [22] and resultant elevations in post-operative P-NGAL levels. On the other hand, many authors have reported U-NGAL as a specific biomarker for prediction of post cardiac surgery AKI [16, 17, 23, 24] and the present study also demonstrated a stronger correlation of U-NGAL with post-operative creatinine as compared to P-NGAL.
Strengths and limitations
This prospective randomised controlled study conducted in patients undergoing on-pump CABG adds novel insights into the impact of GDT-based haemodynamic management on post-operative NGAL profile. To the authors knowledge, the present study is the first of its kind with no literature available on the combined plasma and urinary NGAL profile following the use of GDT in on-pump CABG. The study evaluates the NGAL levels over a range of values across three post-operative time frames in the first 24 h after surgery. The NGAL levels were correlated with the highest creatinine values obtained in the post-operative period, considering the latent period of serum creatinine elevations.
The biomarker-based study has few inherent limitations. Although the study aimed at evaluating the effect of GDT on NGAL profile with a sample size of 120 patients, the sample size falls short of achieving a sizeable number of AKI patients in order to study the diagnostic utility of NGAL in predicting AKI. Although all the subjects in the study had normal pre-operative serum creatinine measurements, an estimation of glomerular filtration rate to document normal kidney function was not performed. The role of peri-operative diuretics in influencing the U-NGAL levels was not considered in the study. Considering the fact that the use of IABP support has been implicated as an independent predictor of peri-operative AKI, the inability of the study to compare the extent of IABP support between the two groups is an inbuilt limitation as the GDT-based management is not compatible with an IABP support.
Conclusion
The novel diagnostic and management concepts in the field of post cardiac surgery AKI constitute an active area of research. The present biomarker-based study describes lower post-operative levels of NGAL with the use of GDT in on-pump CABG. A higher degree of decline in U-NGAL levels in comparison to P-NGAL with the use of GDT elucidates the role of GDT in minimising the renal tubular injury over and above the initial inflammatory response to CPB. Larger prospective studies are required to study the translation of the favourable biomarker profile into improved clinical outcomes with the use of GDT.
Compliance with ethical standards
All procedures performed in this study on human participants were in accordance with the ethical standards of the institutional ethics committee of All India institute of Medical Sciences, New Delhi, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Statement of human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
This article does not contain any studies with animals performed by any of the authors.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
Footnotes
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Contributor Information
Poonam Malhotra Kapoor, Phone: 91-9971000741, Email: drpoonamaiims@gmail.com, Email: docpoonamaiims@gmail.com.
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