Levosimendan improves renal function in acute decompensated heart failure: possible underlying mechanisms.
OBJECTIVE
The cardio-renal syndrome plays a critical role in acute heart failure (HF). Levosimendan, an inodilator drug, has a positive but controversial effect on kidney. Our aim was to evaluate its effects on both renal and systemic haemodynamic parameters as well as on renal function, explaining the possible mechanisms involved.


RESULTS
Patients with acute decompensated HF, moderate renal impairment, wedge pressure >20 mmHg and EF <40% were eligible. Twenty-one patients were randomized to infusion of levosimendan or placebo, on top of standard therapy. Systemic haemodynamic parameters (wedge and cardiac output) were evaluated at baseline and at 8, 16, 24, 48, and 72 h. An intravascular renal artery Doppler exam was performed at baseline, after levosimendan bolus, and 1 h thereafter. Renal blood flow, glomerular filtration rate (GFR), cystatin C, blood urea nitrogen (BUN), urinary output, sodium excretion, and plasma sodium were measured. The effect of levosimendan was beneficial and significantly different from placebo on several renal and cardiac parameters. Specifically, the levosimendan and placebo group exhibited significantly different changes over time in GFR (P = 0.037), renal blood flow (P = 0.037), and renal artery diameter (P = 0.033), with ensuing improvements in serum levels of BUN (P = 0.014), creatinine (P = 0.042), and cystatin C (P = 0.05). Concomitantly, levosimendan provided a significant increase in urine output up to 72 h (P = 0.02). These beneficial results on renal parameters were accompanied by similarly significant and favourable changes in cardiac index (P = 0.029) and PCWP (P < 0.001).


CONCLUSIONS
Levosimendan, in acute decompensated HF, has an immediate renoprotective effect, mediated by an increase in renal blood flow, due to a selective renal arterial and venous vasodilating action.


BACKGROUND
NCT00527059.
Department of Cardiovascular, Respiratory, Nephrologic, Geriatric and Anesthesiological Sciences, Sapienza University of Rome, Policlinico Umberto I, Rome, 00161, Italy.
Francesco
F
Fedele
Noemi
N
Bruno
Bruno
B
Brasolin
Carmen
C
Caira
Alessandra
A
D'Ambrosi
Massimo
M
Mancone
D000368:Aged; D059347:Cardio-Renal Syndrome / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D008297:Male; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan
Heart failure; Kidney; Levosimendan; Regional blood flow