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(1) Background: Acute kidney injury (AKI) is a common complication following thoracic aortic surgery (TAS), with moderate hypothermic circulatory arrest (MHCA). However, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate the role of new biomarkers in patients after MHCA. (2) Methods: 101 consecutive patients were prospectively enrolled. Measurements of urinary [TIMP-2]*[IGFBP7] and Cystatin C in the blood were performed perioperatively. Primary endpoint was the occurrence of AKI stage 2 or 3 (KDIGO-classification) within 48 h after surgery (AKI group). (3) Results: Mean age of patients was 69.1 ± 10.9 years, 35 patients were female (34%), and 13 patients (13%) met the primary endpoint. Patients in the AKI group had a prolonged ICU-stay (6.9 ± 7.4 days vs. 2.5 ± 3.1 days, p < 0.001) as well as a higher 30-day-mortality (9/28 vs. 1/74, p < 0.001). Preoperative serum creatinine (169.73 ± 148.97 µmol/L vs. 89.74 ± 30.04 µmol/L, p = 0.027) as well as Cystatin C (2.41 ± 1.54 mg/L vs. 1.13 ± 0.35 mg/L, p = 0.029) were higher in these patients. [TIMP-2]*[IGFBP7] increased significantly four hours after surgery (0.6 ± 0.69 mg/L vs. 0.37 ± 0.56 mg/L, p = 0.03) in the AKI group. Preoperative Cystatin C (AUC 0.828, p < 0.001) and serum creatinine (AUC 0.686, p = 0.002) as well as [TIMP-2]*[IGFBP7] 4 h after surgery (AUC 0.724, p = 0.020) were able to predict postoperative AKI. The predictive capacity of Cystatin C was superior to serum creatinine (p = 0.0211) (4) Conclusion: Cystatin C represents a very sensitive and specific biomarker to predict AKI in patients undergoing thoracic surgery with MHCA even before surgery, whereas the predictive capacity of [TIMP-2]*[IGFBP7] is only moderate and inferior to that of serum creatinine.
RESUMO
INTRODUCTION: Over the course of critical illness, there is a risk of acute kidney injury (AKI), and when it occurs, it is associated with increased length of stay, morbidity, and mortality. The urinary cell-cycle arrest markers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) have been utilized to predict the risk of AKI over the next 12 h from the time of sampling. The aim of this analysis was to evaluate the utility of [TIMP-2] × [IGFBP7] measured serially to anticipate the occurrence of AKI over the first 7 days of critical illness. METHODS: This analysis is from a prospective, blinded, observational, international study of patients admitted to intensive care units. We designed the analysis to emulate a clinician-driven serial testing strategy. Urine samples collected every 12 h up to 3 days from 530 patients were considered for analysis. We evaluated [TIMP-2] × [IGFBP7] results for the first 3 measurements (baseline, 12 and 24 h) and continued to evaluate additional results if any of the first 3 were positive >0.3 (ng/mL)2/1,000. Patients were stratified by number of [TIMP-2] × [IGFBP7] results >0.3 (ng/mL)2/1,000 and number of results >2.0 (ng/mL)2/1,000. The primary endpoint was AKI stage 2-3 defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: The median (interquartile range) age was 64 (53-74) years, 61% were men, and 79% were Caucasian. The median APACHE III score was 71 (51-93), and 82% required mechanical ventilation. Baseline serum creatinine was 0.8 mg/dL and 164/530 (31%) developed the primary endpoint by day 7 with a median time from baseline to stage 2/3 AKI of 26 (8-56) h. In patients with negative values for the first 3 tests (≤0.3 (ng/mL)2/1,000), the cumulative incidence of the primary endpoint at 7 days was 13.0%. Conversely, for those with one, two, or three strongly positive values (>2.0 (ng/mL)2/1,000), the cumulative incidence for the primary endpoint at 7 days was 57.7, 75.0, and 94.4%, respectively, p < 0.001 for trend. There were 3.4% with test results between 0.3 and 2.0 (ng/mL)2/1,000 at all measurements; one third of those patients developed the primary endpoint. We observed a graded increase in the primary endpoint in Kaplan-Meier plots for successively positive test results over time. CONCLUSION: Serial urinary [TIMP-2] × [IGFBP7] at baseline, 12 and 24 h, and up through 3 days are prognostic for the occurrence of stage 2/3 AKI over the course of critical illness. Three consecutive negative values (≤0.3 (ng/mL)2/1,000) are associated with very low (13.0%) incidence of stage 2/3 AKI over the course of 7 days. Conversely, emerging or persistent, strongly positive results [>2.0 [ng/mL]2/1,000] predict very high incidence rates (up to 94.4%) of stage 2/3 AKI. There was a low rate of test results between 0.3 and 2.0 (ng/mL)2/1,000, where the primary endpoint was observed in a third of cases.