Study Question: How are glomerular filtration rate (GFR), renal blood flow (RBF), and renal oxygen consumption affected by brief exposure to levosimendan after cardiac surgery with cardiopulmonary bypass (CPB)?
Study Description: This was a randomized, placebo-controlled trial of post-cardiac surgery patients with normal baseline renal function. Excluded individuals required inotropic or vasopressor support or developed bleeding postoperatively. Included patients were randomized to postoperative placebo or levosimendan with a 12 mcg/kg bolus dose and a 0.1 mcg/kg/min continuous infusion for < 2 hours. The study used a previously published technique wherein a left renal vein catheter was inserted to measure RBF by retrograde thermodilution prior to and during the study drug administration. Renal oxygen consumption was derived from pre- and post-glomerular samples and GFR was calculated using 51Cr-EDTA extraction.
Results: The study included 15 individuals in each intervention group, with an overall baseline GFR of approximately 65 mL/min. In contrast to placebo, levosimendan significantly increased RBF and GFR from baseline (RBF estimated change = 50 mL/min, p = 0.027; GFR estimated change = 12 mL/min, p = 0.030). Levosimendan patients also exhibited a decrease in renal vascular resistance post-intervention with no clear change in renal oxygen consumption (p = 0.023 and p = 0.128, respectively).
Conclusion(s): Patients with baseline normal renal function showed regional benefit of levosimendan in the kidney after cardiac surgery requiring CPB. Specific improvements included an increase in RBF and GFR without worsening renal oxygenation.
Perspective: Levosimendan, a non-FDA approved calcium sensitizer, secondarily impacts KATP channels on vascular smooth muscle and is thought to elicit pre-glomerular renal vasodilation. The clinical literature as a whole suggest variable effects of levosimendan on renal function (see Yilmaz MB, et al., Cardiovasc Drug Ther., 2013 for a summary of the literature and consensus recommendations). This well-designed study is one of the first of its kind in humans to document unique renal effects of the drug beyond cardiac output augmentation. It would be premature to generalize these findings to a broad array of patients, as this study was confined to hemodynamically stable adults with neither acute nor chronic renal insufficiency undergoing cardiac surgery in which a brief exposure to levosimendan with a bolus dose was administered postoperatively for the purposes of conducting invasive renal hemodynamic and functional measurements. The study is also limited by a small sample size leading to a lack of precision in the estimates and was not designed to assess the clinical impact of these results.