To the best of our knowledge, this is the first study available in medical literature to assess the role of serum NGAL as an early biomarker of CIN after PCI in high-risk patients. The main finding of our study is that serum levels of creatinine and BUN, traditional biomarkers of renal injury, could not detect early development of CIN. In contrast, serum concentrations of NGAL at 6 hours post-PCI could detect patients that are at high risk of developing CIN requiring hemodialysis during hospitalization. Moreover, we also found that NGAL levels were higher in patients who developed CIN and died during hospital admission. This finding is clinically relevant because using serum NGAL concentration, physicians could identify patients at risk of developing CIN that will require hemodialysis early and may benefit from prompt renal specialist consultation and medical interventions, such as optimization of intravascular volume status and avoidance of nephrotoxic medications.
Although our study is the first to use serum NGAL for early detection of CIN in high-risk patients with ACS undergoing PCI; our findings build on prior knowledge that has shown that NGAL is superior to serum creatinine or BUN for early diagnosis of acute kidney injury and CIN. A recent meta-analysis showed that NGAL had an excellent predictive utility for CIN with AUCs of 0.91 for serum NGAL and 0.94 for urinary NGAL [35]. However, in this meta-analysis, authors only included 4 studies that used serum NGAL in adults, and all 4 studies had small sample sizes [35]. Additionally, these studies were in patients who underwent elective PCI, and only one study used the same definition of CIN as our study. Besides this, regarding renal protection protocols, in two of them, patients received normal intravenous saline at a rate of 1 mL/kg per hour previous to the procedure and in only one study patients also received oral N-acetylcysteine (NAC) 600 mg twice daily for 3 days [28, 30, 36]. A more recent study by Nguyen et al. with unselected patients with ST-elevation myocardial infarction treated by PCI and were all patient receive only 1000 mL of physiological saline given at a rate of 0.6 mL/kg per hour for 24 hours except in those patients in Killip class III or IV; plasmatic NGAL did not provide additional value regarding CIN prediction compared with other risk [37].
In contrast, all of our study subjects received per-protocol treatment for renal protection to prevent CIN that included normal saline at a rate of 1 ml/Kg/h IV; N-acetylcysteine 1,200 mg IV BID 24 hours before and 12 hours after the procedure, and sodium bicarbonate started at least 1-hour pre-procedure and continued up to 6 hours post-procedure. Moreover, our study included only high-risk patients identified by Mehran score >11 points, whereas other studies included lower-risk patients, which constitutes the strength and novelty of our results.
The importance of early detection of CIN is that several observational studies have demonstrated that in-hospital mortality is five times higher in patients with CIN that patients who do not have CIN. Added to the above, observational studies have shown that as many as 20% of patients who develop CIN suffer a persistent worsening of renal function [5, 38, 39]. Therefore, early detection of CIN could mean an early consultation to a renal specialist because it has been demonstrated that a delay in nephrology consultation contributes to higher mortality in acute kidney injury [40].
Several urinary and serum biomarkers have been proposed to identify patients at risk of dying due to CIN. However, the results are controversial and not conclusive. In our study, we found that patients with higher concentrations of serum NGAL had higher mortality. Even though this is an exciting finding, our study was not powered nor designed to predict mortality; thus, this finding should be interpreted with caution. However, this might open the possibility to design more prominent, multicentric, prospective studies to evaluate whether NGAL may be used as a prognosis biomarker in patients with CIN and, more specifically, in patients with AKI due to CIN.
Our study has important strengths and limitations that need to be recognized. One of the strengths of our study is that the setting was a highly specialized cardiovascular hospital with established protocols to identify and intervene on patients at risk of CIN. Another strength of our study is the inclusion of only high-risk patients, an important group of patients frequently excluded from other studies. However, it is essential to recognize that the small sample size limits our study due to the recruitment of a specific high-risk patient population. This also limits our ability to the performance of all statistical tests to assess the performance of NGAL as a diagnostic marker in the early detection of patients with CIN requiring hemodialysis. Moreover, only three patients died in our study; thus, we cannot conclude, nor hypothesize the role of NGAL in this regard. It is important to mention that NGAL has been recently associated with heart failure and coronary artery disease possible as a manifestation of inflammation [41]; and essential aspect that needs to be kept in mind because this condition could develop a false positive scenario. Besides this, some patients that required hemodialysis had higher baseline sCr, which could imply some undiagnosed cases of the chronic kidney, which could have an impact on the initial value of NGAL. Nevertheless, the discriminatory power of NGAL at 6 hours superior to creatinine levels at 6 hours to predict the need for hemodialysis. Acute kidney injury is a widely used and accepted definition. However, there are several definitions, and there is controversy about which is the most representative classification. Thus, we did not asses AKI in patients that did not require hemodialysis. Readers should be aware that the data presented in this study only represent patients with severe CIN requiring hemodialysis, and these data should not be extrapolated to other patients. Finally, not all hospitals can ensure nephroprotection in high-risk patients within the first 6 hours of hospital admission. Therefore, the results presented in this study might not be generalizable for all hospitals.