In this retrospective cohort study, we found that after adjusting serum creatinine for the cumulative fluid balance, more patients met KDIGO criteria for CSA-AKI. Patients in underestimation group had worse outcomes than that in normal group or overestimation group in terms of the length of ICU stay, total length of hospital stay and mechanical ventilation dependent days, but not in the incidence of CRRT or in-hospital mortality rate.
Since minimal increase of serum creatinine was associated with adverse outcomes in patients within the ICU setting, precise recognition and accurate assessment of AKI may contribute to the prevention and early intervention of reversible factors [22-24]. Serum creatinine may normally be influenced by several factors, including renal creatinine clearance or creatinine formation or both . Importantly, serum creatinine level can also be affected by dilution effect of fluid resuscitation, which frequently occurs in critically ill patients [6, 26]. Our results indicate that cumulative fluid balance in patients with cardiac surgery underestimates the diagnosis and staging of AKI, which is in accordance with the results from previous studies [14, 18].
Post hoc analysis of Fluids and Catheters Treatment study illustrated that incidence of AKI with acute respiratory distress syndrome was greater in patients managed with liberal fluid protocol than that in conservative fluid protocol after adjustment for fluid balance . Moreover, mortality rate of these patients was similar to those diagnosed with AKI before and after adjustment for fluid balance. Macedo et al. conducted an analysis in patients underwent nephrology consultation for AKI in ICU settings, which showed dilution effect of fluid overload on serum creatinine may delay the diagnosis time for AKI . Previous study focusing on cardiac surgery patients also demonstrated that patients with AKI only after adjustment for fluid balance had intermediate outcomes between non-AKI and classical AKI patients . Similarly, our study demonstrated that patients with underestimation of serum creatinine had prolonged mechanical ventilation dependent days, longer length of ICU stay and hospital stay.
Multivariate analysis of our study also found that after adjustment for relevant risk factors, patients with older age, lower left ventricular ejection fraction, higher baseline serum creatinine and cumulative fluid balance after cardiac surgery were independently associated with the underestimation of serum creatinine. Thus, to minimize underestimation of serum creatinine and improve subsequent predictive ability of poor outcomes, risk factors including age, baseline cardiac function as well as baseline kidney function should be taken into account before fluid administration during perioperative period in cardiac surgery patients.
Nevertheless, there are several limitations in our study. First, as a single center study, regardless of the large cohort of patients, inherent bias of study design still remains to be concerned. Second, the cause of fluid administration was not easily distinguished from our database. Excess fluid administration may be in an effort to improve low cardiac output, and fluid accumulation may be secondary to inflammatory response. Meanwhile, poor outcomes in underestimation group may in part due to the greater colloids infusion via the damage to endothelial glycocalyx [27, 28]. Last, insensitive fluid loss during study period was not calculated, which may influence the accurate measurement of fluid balance, especially within the patients who were intubated during ICU period.
Regardless of these limitations, our study highlights the dilution effect of cumulative fluid balance on serum creatinine and further illustrates associated outcomes in cardiac surgery patients, which may benefit physicians to recognize mild AKI via adjustment for cumulative fluid balance. Strikingly, our study identified for the first time that risk factors including age, baseline cardiac function, and preoperative kidney function were independently associated with the underestimation of serum creatinine, which would be beneficial for screening patients at high risk for misinterpretation of postoperative serum creatinine. However, much more advanced studies should be designed to clarify the underlying association between concealed mild AKI and actual changes of renal function, using the combination of serum creatinine and kidney injury biomarkers to timely detect the deterioration of kidney function after cardiac surgery.