Disturbed synthesis of insulinlike growth factor I and its binding proteins may influence renal function changes in liver cirrhosis

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by t he liver upon stimulation by growth hormone (GH). IGF-1 exerts important ef fects on renal hemodynamics and renal sodium handling. The bioactivity of t his hormone is influenced by its binding proteins (BP) of which IGF-BP3 fav ors retention in the capillary lumen while IGF-BP1 facilitates the transpor t to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target c ells 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 a ddressed the relationship between alterations in this system and renal func tion changes in cirrhosis, In the present study we have included 20 patient s with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of TGF-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 acc essibility of circulating IGF-1 to target cells) was higher in patients wit h 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 nega tive 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.