Background/Aims: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. Methods: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. Results: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p∞0.02) and was directly correlated with the Pugh score (r:

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by the liver upon stimulation by growth hormone (GH). IGF-1 exerts important effects on renal hemodynamics and renal sodium handling. The bioactivity of this hormone is influenced by its binding proteins (BP) of which IGF-BP3 favors retention in the capillary lumen while IGF-BP1 facilitates the transport to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target cells including renal tubules. Although a number of reports have dealt with disturbances of the IGF-1/IGF-BP system in cirrhosis, no studies have yet addressed the relationship between alterations in this system and renal function changes in cirrhosis. In the present study we have included 20 patients with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of IGF-1 and IGF-BP3, higher IGF-BP1 levels, and a tendency to higher insulinemia and GH values. The index IGF-1 x IGF-BP1/IGF-BP3 (IGF-1-IGF-BP index, reflecting the accessibility of circulating IGF-1 to target cells) was higher in patients with ascites. IGF-1 directly correlated with renal blood flow (P < 0.05), with IGF-BP3 (P < 0.001) and inversely with the Pugh's score (P < 0.02). A negative correlation was found between IGF-1-IGF-BP index and fractional sodium excretion (P < 0.01) and between IGF-BP1 and urinary sodium excretion (P < 0.02). Our findings support the hypothesis that the disturbance of the IGF-1/IGF-BP axis may be related to the degree of renal vasodilation and renal sodium retention in cirrhotic patients.

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