The hepatorenal syndrome is a syndrome of advancing renal failure in a patient with severe hepatocellular failure, usually advanced cirrhosis. In most instances, the uremia and oliguria that characterize this syndrome arise either spontaneously or in response to changes in blood volume or fluid shifts within body compartments. Patients are seldom admitted with this diagnosis; its development is usually precipitated by events in the hospital, which may include overly vigorous diuretic therapy, diarrhea or GI bleeding. The histology of the kidneys is virtually normal, with the renal failure being a functional failure. Such kidneys have been successfully transplanted and have functioned normally. Conversely, if hepatic function is restored by liver transplantation, kidney function may return to normal. In this syndrome there are abnormalities in renal blood flow, including active renal vasoconstriction, thus decreasing effective renal circulation, especially to the renal cortex. The cause of this is unknown, but is best thought of as an imbalance between systemic vasodilators and renal vasoconstricting mechanisms.

In the early stages, renal dysfunction is characterized by failure to excrete a water load, a reduction in the urinary sodium to <10 mEq/L and a progressive hyponatremia (Table 22). Ascites is usually present. As the syndrome progresses there is increasing azotemia, usually with hepatic failure and increasing difficulty controlling the ascites. Sodium is avidly reabsorbed with increasing urinary osmolality. The patient becomes drowsy, nauseated and thirsty. Terminally, the patient's blood pressure drops, coma deepens and urine volume falls further. The terminal stages may last a few days to weeks.

Clinically, it is important to distinguish hepatorenal syndrome from other causes of renal failure. Iatrogenic renal failure must be ruled out, including drug-induced disease from aminoglycosides and nonsteroidal anti-inflammatory medication. Hepatorenal syndrome must also be distinguished from prerenal azotemia and acute tubular necrosis. Acute tubular necrosis has a high urinary sodium. Although prerenal azotemia may show similar tubular function, this is ruled out by the clinical setting in which hepatorenal syndrome occurs and the lack of sustained benefit by expansion of intravascular volume with colloid replacement. In addition, cirrhosis, especially alcoholic cirrhosis, may leave glomerular mesangial deposits of IgA, which is diagnosed by the presence of proteinuria with microhematuria and casts. Hepatitis B can cause glomerulonephritis, which should be detectable because of red cell casts and proteinuria. Acetaminophen toxicity can also cause concomitant liver and renal failure with high urinary sodium excretion.

Treatment of established hepatorenal syndrome is difficult. Thus, emphasis is toward prevention by avoiding diuretic overdose, treating ascites slowly and recognizing complications early, including electrolyte imbalance, hemorrhage and infection. Conservative management includes the restriction of fluids, sodium and potassium. All potentially nephrotoxic drugs should be withdrawn and a septic workup should be carried out. Volume expansion with albumin results in only transient improvement. Isotonic saline is usually avidly retained, worsening the ascites and possibly precipitating pulmonary edema. Mannitol is not used, as this may lead to intracellular acidosis. Dialysis does not improve survival. The final combination of azotemia, hyponatremia and hypotension is terminal. Liver transplantation should be considered, but presumably would have been offered to the patient earlier in the course of the hepatic illness.