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Cardio-Renal Effects of the A1 Adenosine Receptor Antagonist SLV320 in Patients with Heart Failure
Circulation: Heart Failure, 10/07/09

Mitrovic V et al. – SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis.

Exclusive Author Commentary
Berthold Hocher, 10/08/09

short commentary Heart failure is still one the most common reasons for hospitalization in developed countries with an aging population worldwide. A substantial proportion of patients with acute heart failure show significant renal dysfunction. Treatment of congestive heart failure itself is limited by worsening renal function despite persistent volume overload. This connection between heart failure and renal dysfunction has been termed the cardio-renal syndrome and has made treatment of patients with stable and unstable heart failure difficult. Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists like SLV320 seems to improve diuresis and sodium excretion without compromising glomerular filtration rate in heart failure patients. The current study confirmed existing clinical data in CHF patients using, however, for the first time in a hemodynamic CHF clinical study a biomarker for glomerular filtration rate: cystatin C. Using this biomarker, we demonstrated a fast and sustained improvement of GFR after SLV320 infusion. Cystatin C thus might be a biomarker even suitable to describe acute renal effect of new drugs in clinical research. This study analyzed also for the first time direct cardiac effects of A1 adenosine receptor antagonists. We demonstrated that SLV320 has no direct effects on heart rate, blood pressure, PCWP, MPAP, SVR, RAP, and CO. We concluded that SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis. It remains to demonstrate that these immediate renal effects translate into clinical benefits on the long-run. Prof. Dr. Berthold Hocher Center for Cardiovascular Research/Institute of Pharmacology Charité Hessische Str. 3-4 10115 Berlin Germany Tel.: +49-30 450 514098 Fax: +49-30 450 514938 E-mail: berthold.hocher@charite.de

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