Neutrophil Gelatinase-associated Lipocalin, Cystatin C and Matrix Metalloproteinase-9 as Possible Biomarkers in Early Detection of Acute Kidney Injury after Cardiac Surgery

IntROduCtIOn Acute kidney injury is a serious and fatal complication that occurs in 1-2% of patients after cardiac surgery [1,2]. Patients with AKI need dialysis; mortality among these patients is over 60% [1,2]. In less severe AKI, cases that do not need dialysis, short-term mortality increases 19-fold [3]. In mild AKI in which serum creatinine levels increase by 25%, over a long time to 10 years after surgery, mortality is doubled [4]. It is thought that the most important mechanism of kidney injury is intraoperative ischaemia-reperfusion injury. The obtained results from animal studies have indicated that AKI may recurr when the therapeutic intervention is performed at the shortest time after surgery or during the beginning time or at the early extension phase of ischaemia-reperfusion injury [5-8]. It has been determined that kidney injuries are partly caused due to lack of specific and real-time sensitive markers that cannot achieve early diagnosis of AKI [9]. Right now, serum creatinine is the AKI diagnostic marker; however, its increase is delayed, which causes postponement of the treatment processes [10,11]. Serum creatinine is not a precise marker for Glomerular Filtration Rate (GFR) in stable condition [12]; therefore, acute changes in serum creatinine at the time of AKI may lack proper precision and may not accurately reflect the severe changes in GFR. Many studies have been performed in the clinical care and clinical trials to find biomarkers for early diagnosis of AKI with the aim of achieving more time for AKI treatment [13,14]. Although, there have been some advances in this field, creatinine is still the common reference for comparing new biomarkers of kidney injury [15]. Cys C as a novel biomarker is detected in serum earlier than creatinine (about 24-48 hours). Cys C is not affected by tubular secretion and glomerular filtration; so urine Cys C can reflect the glomerular filtration function as well as its serum concentration [16]. Cys C is a much more precise estimator of GFR than creatinine and it has more diagnostic value for chronic kidney disease [12,17]. Some studies have demonstrated the importance of Cys C in early detection of kidney injury after heart surgery [18,19]. Cys C concentration increases within two hours after heart surgery and reaches to a peak at six hours after cardiopulmonary bypass [20]. Another novel marker for AKI is urinary NGAL. Different clinical studies have indicated that increase in serum and urine NGAL is an independent predictor of serum creatinine for AKI diagnosis [21,22]. A meta-analysis had shown the diagnosis and prognosis accuracy of NGAL for AKI identification [9]. Also, it is reported that urinary NGAL significantly reaches to its peak (400 ng/mL) within 2-4 hours after AKI [23]. Similar to Cys C, NGAL can be a better marker than creatinine. Expression of various MMPs is different in different parts of kidney; for example, MMP-9 is widely expressed in the glomerulus and is considered as a prognostic factor in patients undergoing surgery [24]. The role of MMPs has been demonstrated in the pathophysiology of numerous chronic and acute renal diseases such as renal ischaemic Sara Bagheri1, Nahid eiNollahi2, MohaMMad Taghi goodarzi3, haSSaN TaTari4, heMeN Moradi-Sardareh5, NaSriN Sheikh6