Plasma Cystatin C and Acute Kidney Injury after Cardiopulmonary Bypass

Background and objectives: Little is known about the performance of plasma cystatin C (CysC) in patients undergoing cardiopulmonary bypass (CPB) and its utility in the early diagnosis of acute kidney injury (AKI). In this post hoc analysis, the goal was to determine whether plasma cystatin C, measured 2 hours after the conclusion of CPB, is a reliable marker of AKI.Design, setting, participants, & measurements: Plasma CysC was measured in 150 patients undergoing CPB at the following times: preoperatively, 2 hours after the conclusion of CPB, postoperative day 1, and postoperative day 2. Plasma CysC levels were related to the development of AKI as defined by an increase in serum creatinine of ≥50% or ≥0.3 mg/dl from baseline up to 3 days postoperative. Mixed linear models were used to evaluate the relationship of serial plasma CysC values with AKI. The discriminatory capacity of plasma CysC was estimated using receiver operating characteristic curves. Logistic regression was utilized to assess the adjusted relationship between plasma CysC and subsequent AKI.Results: AKI developed in 47 (31.3%) patients. Plasma CysC was higher at all times among patients who developed AKI compared with those who did not (P < 0.0001). The discriminatory capacity of plasma CysC measured preoperatively and 2 hours after the conclusion of CPB was modest.Conclusions: Serial measures of plasma CysC are highly correlated with the development of AKI. However, the discriminatory capacity of plasma CysC as an early marker of AKI remains limited.Acute kidney injury (AKI) is a common and serious complication of cardiac surgery and cardiopulmonary bypass (CPB) (1,2). Current diagnostic criteria for AKI are based on the presence of relative or absolute increments in serum creatinine (sCr) (3). Although readily available and widely used, sCr is a suboptimal marker of AKI for several reasons: sCr concentration is affected by nonrenal factors (e.g., muscle mass and distribution volume); creatinine is secreted by the renal tubules and serum concentrations do not entirely reflect glomerular filtration; and in the setting of acute injury, elevations in sCr usually do not occur until well after the time of the actual insult. Discovery of an alternative marker that reliably reflects kidney function in the acute setting and enables the early detection of AKI would be very desirable.Cystatin C (CysC) is a 13-kD cysteine protease inhibitor that is synthesized in all nucleated cells at a steady state. It is freely filtered by the glomerulus, not secreted by renal tubules, and completely metabolized at the level of the renal tubules. These properties have made it an attractive marker of the GFR in chronic kidney disease (4,5). However, receipt of glucocorticoids, age, gender, and C-reactive protein are nonrenal factors that may affect the measurement of plasma CysC (6,7). There is a relative paucity of information on the plasma levels of CysC after acute kidney insults such as those associated with CPB. We therefore undertook a three-center cohort study that evaluated the performance of plasma CysC as an early diagnostic marker for AKI as compared with a reference standard based on sCr elevation from baseline. We also assessed the ability of plasma CysC to discern patients with AKI from those without AKI after cardiac surgery requiring CPB.