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 with underestimation of serum creatinine had worse outcomes in terms of length of ICU stay, total length of hospital stay and mechanical ventilation dependent days, but not in the incidence of CRRT and 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 risk 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 is frequently occurs in critically ill patients [6, 26]. Our results indicate that cumulative fluid balance in patients with cardiac surgery somewhat underestimates the diagnosis and staging of AKI, which is in accordance with previous studies [14, 18].
Post hoc analysis of Fluids and Catheters Treatment study illustrated that the incidence of AKI with acute respiratory distress syndrome was greater in those managed with liberal fluid protocol than conservative fluid protocol after adjustment for fluid balance . Moreover, mortality rate of these patients was similar to patients diagnosed with AKI before and after adjustment for fluid balance. Macedo et al. conducted analysis in patients underwent nephrology consultation for AKI in ICU, which showed dilution effect of fluid overload on serum creatinine may delay diagnosis time for AKI . 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 . Our study demonstrated that patients with underestimation of serum creatinine had prolonged mechanical ventilation dependent days, longer length of ICU and hospital stay.
Multivariate analysis of our study also found out that after adjustment for relevant risk factors such as patients with older age, lower left ventricular ejection fraction, higher baseline serum creatinine and severe extent of cumulative fluid balance after cardiac surgery were independently associated with underestimation of serum creatinine. Thus, to improve underestimation of serum creatinine along with subsequent predictive ability of poor prognosis, risk factors including age, baseline cardiac function as well as baseline kidney function should be taken into account before fluid administration in patients undergoing cardiac surgery. Nevertheless, there are several limitations in our study. First, as a single center study, regardless of the large cohort of our cardiac surgery 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 manage low cardiac output, and fluid accumulation may be secondary to inflammatory response. Last, insensitive fluid loss during study period was not taken into account, which may influence the accurate measurement of fluid balance, especially with patients that were intubated during ICU period.
Regardless of these limitations, our study highlights 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 the risk factors including age, baseline cardiac function, and preoperative kidney function were independently associated with the underestimation of serum creatinine, which could contribute to 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, such as using the combination of serum creatinine and kidney injury biomarkers to timely detect deterioration of kidney function after cardiac surgery [27, 28].