Intraoperative Urinary Biomarkers and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVES: To evaluate the association of intraoperative urinary biomarker excretion during cardiac surgery and the subsequent development of acute kidney injury (AKI). DESIGN: Prospective, nonrandomized, observational study. SETTING: Single tertiary-level, university-affiliated hospital. PARTICIPANTS: Ninety patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urinary samples were collected every 30 minutes intraoperatively and then at four, 12, and 24 hours after CPB. Samples were measured for interleukin 18 (IL-18), kidney injury molecule-1 (KIM1), and creatinine concentrations. Urinary biomarker excretion (raw and indexed to creatinine) for four intraoperative and three postoperative points were compared between patients with and those without subsequent AKI defined by increased serum creatinine concentration ≥0.3 mg/dL within the first 48 hours or ≥1.5 times baseline within seven days. Raw and indexed median IL-18 values were similar between AKI groups at all intraoperative points, but became significantly different at 12 hours after CPB. Raw and indexed median KIM1 values were significantly different between AKI groups at multiple intraoperative points and at four and 12 hours after CPB. During intraoperative and postoperative points, patients in the fourth quartile of KIM1 excretion had greater AKI incidence and longer intensive care and hospital lengths of stay than those in the first quartile. Only postoperatively did the differences in these outcomes between the fourth and first quartile of IL-18 excretion occur. CONCLUSIONS: Intraoperative KIM1 but not IL-18 excretion was associated with postoperative development of AKI.

Effects of curcumin and ursolic acid on the mitochondrial coupling efficiency and hydrogen peroxide emission of intact skeletal myoblasts.

Curcumin may improve blood glucose management, but the mechanism is not fully established. We demonstrated that curcumin (40 µM) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption coupled to ATP synthesis) of intact skeletal muscle cells. A 30-minute pretreatment with curcumin reduced mitochondrial coupling efficiency by 17.0 ± 0.4% relative to vehicle (p < 0.008). Curcumin pretreatment also decreased the rate of hydrogen peroxide emission by 43 ± 13% compared to vehicle (p < 0.05). Analysis of cell respiration in the presence of curcumin revealed a 40 ± 4% increase in the rate of oxygen consumption upon curcumin administration (p < 0.05 compared to vehicle). No difference in mitochondrial coupling efficiency was observed between vehicle- and curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The interaction between curcumin and ursolic acid, another natural compound that may improve blood glucose management, was also examined. Pretreatment with ursolic acid (0.12 µM) increased the mitochondrial coupling efficiency of intact cells by 4.1 ± 1.1% relative to vehicle (p < 0.008) and attenuated the effect of curcumin when the two compounds were used in combination. The observed changes to mitochondrial coupling efficiency and hydrogen peroxide emission were consistent with the established effects of curcumin on blood glucose control. Our findings also show that changes to mitochondrial coupling efficiency after curcumin pretreatment may go undetected unless cells are assessed in the intact condition.