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Objectives Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker. Rationale and Design Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis. Patients Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both “in vivo” and “in vitro.” Main Results In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4 ± 0.38, 1.7 ± 0.41, 2.4 ± 0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2 ± 0.09, 1.4 ± 0.23, 2.2 ± 0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (–18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin (–29%, p < 0.01). This last finding was replicated ex vivo by incubating podocyte primary cell cultures with low-dose ouabain. Conclusions Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.

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A variety of fluid solutions can be used as intravascular replacement for surgical volume loss, and to avoid or delay blood transfusions. Crystalloid solutions, such as Ringer lactate, are typically administered at a rate of 3 or 4 times the volume of blood loss caused by continuous rapid extravasations. Approximately 20% of the volume initially administered remains in the intravascular space hours later. Therefore, rapid infusion of large amounts of crystalloid solutions can cause problems in elderly patients with limited cardiovascular reserve, and can lead to pulmonary and systemic edema. Alternatively, a commonly used synthetic colloid, hydroxyethyl starch (HES), readily allows for a 1:1 replacement ratio of intravascular volume to shed blood, and remains in the intravascular space longer compared with crystalloid solutions. However, HES can induce coagulopathy during prolonged surgical procedures because of the reduced release of factor VIII, von Willebrand Factor (vWF), and impaired platelet function.There are many types of HES according to molecular weight (MW) and degree of substitution (DS). In general, HES with a low MW and low DS is preferred because HES solutions with a high MW and high DS are harder to metabolize and eliminate from the intravascular space. This prolonged stay results in extended adverse effects on coagulation. Six percent HES with a MW of 130 kDa and a DS of 0.4 in a saline medium (Voluven, Fresenius Kabi, Germany) has the lowest MW/DS ratio among other HES on the market and therefore is purported to induce less coagulation impairment. This review of crystalloid and colloid fluid replacement alternatives explores recently published evidence of the clinical utility of Voluven.