The natural history and management of hepatorenal disorders: from pre-ascites to hepatorenal syndrome

In cirrhosis, the natural history of hepatorenal disorders starts with a pre-ascitic stage and is followed by the development of ascites; hepatorenal syndrome (HRS) begins with compensated renal sodium retention, or preascites. In pre-ascites, the renal sodium retaining tendency leads to 'overfilling' of total blood volume, with increased glomerular filtration rates (GFR), overcoming the renal sodium retaining tendency possibly due to renal accumulation of angiotensin II. As peripheral vasodilatation increases, the vascular capacity (in effect the arterial blood volume) becomes inadequately filled, GFR falls, compensatory vasoconstrictors rise, and the resulting renal sodium retention results in diuretic-responsive ascites formation. Increasing proximal reabsorption of sodium results in ascites refractory to diuretic therapy. Repeated abdominal paracentesis will not prevent insidious progression to HRS type II, nor to the precipitation of HRS type I. In contrast, liver transplantation, or transjugular intrahepatic hepatoportal stent shunt (TIPS) in refractory ascites, may prevent the onset of, or reverse, HRS. However, recent non-controlled studies indicate exciting possibilities of medical therapy reversing HRS.