Rani biokemijski biljezi i napredni hemodinamski nadzor u procjeni uzroka akutne ozljede bubrega u djece nakon kardiokirurškoga liječenja [Early biomarkers and advanced hemodynamic monitoring in assessment of acute kidney injury causes in children after cardiac surgery]

Cardicac surgery associated acute kidney injury (CSA-AKI) is a common and serious complication in children. It is defined by appropriate criteria based on acute serum creatinine (SCr) rise and/or diuresis reduction. One of the most frequently used criteria in children is the pRIFLE criterion. It is known that SCr is a late and unreliable marker for CSA-AKI. The discovery of new biomarkers, such as NGAL, KIM-1 and CysC, allow an earlier diagnosis of acute kidney injury than SCr. However, previous clinical studies on the evaluation of these early biomarkers in the diagnosis of CSA-AKI in children have shown contradictory results. The pathogenesis CSA-AKI is very complex and undefined. In the literature it is often stated that the reduced cardiac index (CI) is one of the most important risk factors for CSA-AKI development. However, in children, the criteria for reduced CI after cardiac surgery are still undefined, and so are the limit values at which reduced CI represents a risk factor for the development CSA-AKI. The advanced hemodynamic monitoring system PiCCO allows measurement of CI as well as its most important hemodynamic variables: preload, contractility and afterload. Owing to continuous venous oximetry, it is possible to measure the oxygen delivery and oxygen consumption index (DO2I and VO2I). According to available literature no relevant research has yet been published on the use of the PiCCO system for predicting the development and estimating the cause of CSA-AKI development in children. Likewise, the role of CI, DO2I and the individual hemodynamic and oxygenation parameters measured by the PiCCO system in the CSA-AKI development estimation are currently unknown. The aim of this prospective study is to estimate the joint contribution of early biomarkers, hemodynamic and oxygenation parameters measured by the PiCCO system in the early emergence of of CSA-AKI in children. In order to verify the hypothesis and achieve the aim of the study, we have included 100 patients with heart failure that had undergone cardiac surgery. The primary outcome was the development of CSA-AKI according to pRIFLE criteria. Patients were divided into two groups: the AKI and the non-AKI groups. In all patients hemodynamic and oxygenation parameters and early biomarkers prior to the onset of CPB and 2, 6, 12 and 24 hours after CPB were measured. The values before the CPB were used as baseline values. Patients in the AKI group had significantly lower CI values at all time points of measurement. The cardiac index with defined cut-off values is an excellent predictor of CSA-AKI development, and the best sensitivity and specificity ratio was recorded in the first 12 hours. Also patients in the AKI group had significantly decreased globale ejection fraction (GEF), cardiac power index (CPI), global enddiastolic volume index (GEDVI) and systemic vascular resistance index (SVRI). Each of these constituent variables of CI, with defined cut-off values, can predict the development of CSA-AKI. Significantly lower values of DO2I and saturation of central venous blood oxygen (ScvO2) were observed in the AKI group along with significantly higher oxygen extraction rate (OER) and equal VO2I compared with the non-AKI group. All these oxygenation parameters, except for VO2I, may, with defined cut-off values, predict the development of CSA-AKI. The best predictor within the first 12 hours after CPB is DO2I. The observance of significant correlations between CI and DO2I suggests that CI is one of the most important components of DO2I in cardiac surgery patients. The observation of significant correlation between DO2I, VO2I and OER suggests that oxygen consumption in cardiac surgery patients depends primarily on its delivery. In this study we have confirmed that SCr is a late and unreliable marker, especially for the diagnosis of severe forms of CSA-AKI, and that diuresis is a completely unreliable criterion. On the other hand, measurement of early biomarkers (plasma CysC, urine and plasma NGAL, and urine KIM-1), individually and in combination, can predict the development of CSA-AKI already in the first hours after CPB. The best individual predictors of CSA-AKI are plasma CysC and urine NGAL, and the best combination of bimarkers is (+CysCpl and/or +NGALu), which improves the individual predictive characteristics of plasma CysC and urine NGAL. The results of this study have shown a significant negative correlation between the values of CI and DO2I with eraly bimarkers values. The lowest CI and DO2I dynamics overlap with the dynamics of the highest values of early biomarkers in AKI patients. The CI and DO2I values were best correlated with plasma CysC and urine NGAL values. Thus, we have confirmed that the reduced CI and DO2I in combination represent one of the most important causes of CSA-AKI, which can be diagnosed in time with the help of early biomarkers. Finally, in this study we have shown that the combination (+CI and +DO2I and +CysCpl) is the best predictor of CSA-AKI development, because it improves the diagnostic characteristics of individual markers within that combination. This confirms our assumption that simultaneous measurement of CI and DO2I by an advanced hemodynamic monitoring system PiCCO and early biomarkers (in this case CysC in plasma) can improve the detection of early development of CSA-AKI in children