الفهرس 
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Abstract
Acute kidney injury (AKI) previously referred to as acute renal failure (ARF) after cardiac surgery is a well-known, yet incompletely understood, entity that has significant implications on both short- and long-term outcomes and is one of the most serious complications during the postoperative period. The development of AKI after cardiopulmonary bypass (CPB) is associated with a significant increase in infectious complications, an increase in length of hospital stay, and greater mortality when compared with patients without AKI after CPB.
There are more than 35 definitions of AKI in the literature, but without a universally accepted definition for AKI. The term AKI is used to reflect the entire spectrum of what is defined as the abrupt reduction in renal function, in hours or days, in which ARF is characterized by a decrease in the glomerular filtration rate (GFR) and/or urinary volume, in addition to the loss of basic functions; such as the inability to maintain the hydro-electrolyte and basic acid balance till the onset of structural changes, and from prerenal azotaemia to acute tubular necrosis (ATN).
Recently two very similar definitions and staging systems for AKI have been proposed by the Acute Dialysis Quality Initiative group (ADQI) which is the RIFLE and the AKIN classifications. Few years later the Kidney Disease Improving Global Outcomes (KDIGO) work group began by defining AKI by harmonizing the prior RIFLE and AKIN criteria in order to establish a single definition and classification of AKI for practice, research and public health.
In AKI, serum creatinine was proved to be a poor reflection of kidney function for many reasons; for example, a large amount of renal mass can be lost without appreciable changes in serum creatinine because of a concept known as “renal reserve” and it is also influenced by several non-renal factors, including body weight, age, gender, drugs, muscle metabolism, and protein intake.
The pathophysiological features of CSA-AKI are complex and multifactorial including numerous factors: exogenous toxins, endogenous toxins, metabolic factors, ischaemia–reperfusion injury, micro-embolization, neuro-hormonal activation, inflammation, oxidative stress, and haemodynamic factors.
Overall, the therapeutic approaches for the management of AKI in humans have been greatly disappointing; primarily because the treatments were initiated on the basis of elevation of serum creatinine; a late and unreliable measure of kidney function in AKI and the lack of early markers for AKI, and hence a delay in initiating timely therapy; so that recent efforts have, therefore, focused on identifying potential biomarkers of early AKI.
And the objective of this prospective study was (i) to study the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary kidney injury molecule-1 (uKIM-1) as biomarkers for early detection of acute kidney injury in patients undergoing coronary artery bypass graft (CABG) under cardio-pulmonary bypass, so as to find new tools for early diagnosis and assessment of severity of acute kidney injury, hoping to decrease morbidity and mortality rates in hospitalized patients and (ii) to correlate between uNGAL, uKIM-1, complete urine analysis, the other conventional markers of AKI (serum creatinine), and the clinical measurements as regard early diagnosis and prognosis of AKI after CABG.
This study was carried out in Alexandria Main University Hospital on 45 patients of both sex, their age varies between 18-75 years with Cleveland clinic score (CCS) of (0-5) scheduled for elective CABG using cardiopulmonary bypass.
In this study 11 out of 45 patients developed AKI diagnosed by AKIN criteria (as increase in serum creatinine by >0.3 mg/dl from base line within the first 48 hours postoperatively) with no patients required renal replacement therapy. Also, the anaesthetic management and CPB perfusion were standardized in all patients aiming at maintaining adequate perfusion of various body organs.
Measurements were divided to preoperative investigations to assess patients renal function (urea, sCr, and creatinine clearance); assessment of the AKIN stages after ICU admission and every 6 hours for the first 72 hours postoperative; urinary examination for NGAL, KIM-1 (after induction, 2, 6, 12, and 24 hour after termination of CPB), and urinary sediment microscopic examination (preoperative, 2, 12, 24, and 48 hour after termination of CPB); haematological measurements (sCr, and blood urea) just before anaesthesia and every day for 3 days after the end of surgery; and clinical measurements including (duration of anaesthesia and surgery, CPB and aortic cross clamping times, total amount of packed RBCs given during surgery, weaning from the ventilator postoperatively, and intra and postoperative complications).
The demographic results didn’t show any significant difference between both groups as regard age or gender with more females in the AKI group. On comparing the CCS between the two groups it was found to be higher in the AKI patients. Also on assessing the AKIN stages in both groups it was significantly higher in the AKI group than the non-AKI group (starting from 24 hour after surgery till third postoperative day) either due to increased serum creatinine in some patients or decreased urine output in others.
And as regard the CPB time and aortic cross-clamp time were significantly higher in the AKI group. It was noticed that the amount of postoperative bleeding and perioperative requirement for blood transfusion were higher in the AKI patients than non-AKI group. Also the separation from the CPB was done without difficulties in both groups with no difference between them as regard dose of inotropic and vasopressor drugs (dopamine and adrenaline) and only the duration of dopamine infusion was noticed to be higher in the AKI group.
Transient intraoperative complications occurred without affecting patients’ haemodynamics in the form of atrial fibrillation in 7 patients, S-T segment changes in 4 patients, and 4 patients with ventricular fibrillation in both groups without difference between them.
On blood analysis for urea and creatinine it was found that serum creatinine started to rise from the second postoperative day and was higher in the AKI group than the non-AKI one and estimated GFR was significantly lower in the AKI patients after the first postoperative day.
During microscopic urine analysis, it was found that the amount of epithelial cells and granular casts (urine sediment score (USS)) were higher in the AKI patients and this appeared as early as just 2 hours after termination of CPB and continued to be higher in this group till the 2nd postoperative day with an area under the curve (AUC) range of (0.636-0.888).
Also, urinary NGAL was observed to be significantly higher in AKI group at 2 and 6 hours after CPB termination with AUC of (0.710 and 0.700) and corresponding predicted cutoff values of (82.75 and 92.84)ng/ml respectively. Urinary KIM-1 was higher at the end of the first postoperative day than before surgery with values significantly higher in AKI patients at 12 and 24 hour intervals after CPB termination with corresponding AUC of (0.725 and 0.703) which were significant giving a predicted cutoff values of (8.4 and 9.95) ng/ml respectively.
Besides that, it was noted that the combination of both urinary NGAL and KIM-1 yielded a higher AUC of 0.801 denoting an increased diagnostic power of this combination. On adding USS to the previous combination it was noticed that the AUC increased significantly to be 0.906 with a 95% CI (0.812-1.001) giving a near perfect combination for accurate prediction of CSA-AKI.
And the correlation studies showed that USS had a positive relationship with most of the clinical parameters in both groups. UKIM-1 was found to have a negative relationship with most of the clinical parameters especially in the non-AKI group more than the AKI group supporting the protective role of it in acute kidney injury early in its course. But uNGAL correlated poorly with the majority of the clinical measurements in both groups except with bleeding and CPB time there was a significant weak positive relationship.
Also on performing Logistic regression analysis on the various clinical measurements, demographic data, serum creatinine, urine sediment score 48hr after CPB, and the urinary biomarkers assessed and it showed that urine sediment score 48hr after CPB, uNGAL 6hr after CPB, and aortic cross-clamp time were the most powerful independent predictors of AKI.
from the present study we concluded that:
Beside CPB effect on renal injury; blood transfusion, postoperative bleeding, and perioperative haematocrit were found to have an impact on kidney injury.
Although urinary microscopic examination has been neglected for many years by physicians, it was found to be a near ideal renal biomarker with very high sensitivity and specificity and injury site informative.
the rapid response (within few hours) enables NGAL to potentially identify injured kidney much earlier than was previously possible, and makes it a possible powerful sensitive early biomarker of AKI that precedes the increase in serum creatinine by several hours to days.
KIM-1 has been proven to be more specific to ischaemic renal injury with early response in the first postoperative day and its combination with the sensitive NGAL may enable more accurate prediction of CSA-AKI.