Levosimendan Improves GFR in Cardiorenal Syndrome

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In patients with heart failure and renal impairment, the calcium sensitizer levosimendan is associated with improved kidney function, compared to no improvement with dobutamine, reports a randomized trial in the open-access Journal of the American Heart Association.

The double-blind trial included 32 patients with chronic heart failure, left ventricular ejection fraction (LVEF) less than 40%; and impaired renal function. Most patients were men in New York Heart Association class III; the most common cause of heart failure was dilated cardiomyopathy. The mean age was 58 years.

Patients were randomly assigned to receive levosimendan, loading dose 12 µg/kg plus 0.1 µg/kg/min; or dobutamine, 7.5 µg/kg/min) for 75 minutes. Mean LVEF was 27.2% in the levosimendan group and 26.0% in the dobutamine group; mean eGFR was 49.4 and 55.3 mL/min/1.73 m2, respectively.

Both groups underwent measurement of systemic hemodynamics via pulmonary artery catheter. In addition, a renal artery catheter was placed for measurement of renal plasma flow by the infusion clearance technique for para-aminohippurate (PAH), corrected by renal extraction of PAH. Renal extraction of chromium ethylenediamine tetraacetic acid was used to assess filtration fraction. Changes in renal artery blood flow, GFR, and renal oxygenation were compared between groups.

The two treatments resulted in similar increases in stroke volume index, cardiac index, systemic oxygen delivery, and mixed venous oxygen saturation. Renal blood flow also increased to a similar extent in both groups: by 22% with levosimendan and 26% with dobutamine.

In contrast, levosimendan caused a 22% increase in GFR, compared to no change in the dobutamine group. There was no change in filtration fraction with levosimendan, compared to a 17% decrease with dobutamine. There were no serious adverse events.

Management of cardiorenal syndrome in patients with advanced heart failure poses difficult challenges. Inotropic drugs are an option for selected patients with severely reduced cardiac output with compromised perfusion of the kidney and other organs. In previous studies, levosimendan has shown beneficial effects on renal function in acute and chronic heart failure.

In this trial of short-term inotropic infusion for patients with heart failure and renal impairment, levosimendan and dobutamine produce similar increases in renal blood flow. However, levosimendan increases GFR, which dobutamine does not.

The results suggest “a preferential dilation of preglomerular afferent arterioles,” the researchers write. They conclude: “Based on these findings, levosimendan may be the preferred inotropic drug for treatment of patients with the cardiorenal syndrome” [Lannemyr L, et al. Differential effects of levosimendan and dobutamine on glomerular filtration rate in patients with heart failure and renal impairment: A randomized double-blind controlled trial. J Am Heart Assoc 2018; DOI: 10.1161/JAHA.117.008455].