No abstract

Background Acute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support. Methods In this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70–80 mmHg. Intra-group differences were tested by Mann–Whitney U-tests, and a linear mixed model was used to test time and group interaction. Results Twenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (− 18% vs. − 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012). Conclusions In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation. Trial registration NCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1

OBJECTIVES Acute kidney injury is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In this experimental animal study, we evaluated the effects of atrial natriuretic peptide (ANP) on renal function, perfusion, oxygenation and tubular injury during CPB. METHODS Twenty pigs were blindly randomized to continuous infusion of either ANP (50 ng/kg/min) or placebo before, during and after CPB. Renal blood flow as well as cortical and medullary perfusion was measured. Blood was repeatedly sampled from the renal vein. Glomerular filtration rate was measured by infusion clearance of 51Cr-EDTA. RESULTS Glomerular filtration rate was higher (P < 0.001), whereas renal blood flow or renal oxygen delivery was not affected by ANP during CPB. Renal oxygen consumption did not differ between groups during CPB, whereas renal oxygen extraction was higher in the ANP group (P = 0.03). Urine flow and sodium excretion were higher in the ANP group during CPB. Blood flow in the renal medulla, but not in the cortex, dropped during CPB, an effect that was not seen in the animals that received ANP. CONCLUSIONS ANP improved renal function during CPB. Despite impaired renal oxygenation, ANP did not cause tubular injury, suggesting a renoprotective effect of ANP during CPB. Also, CPB induced a selectively reduced blood flow in the renal medulla, an effect that was counteracted by ANP.