Hepatorenal syndrome is characterized by functional kidney failure in patients with end-stage liver disease. It results in intense renal vasoconstriction without any other identifiable kidney pathology. Clinical features of hepatorenal syndrome include oliguria, dilutional hyponatremia, progressive azotemia, and hypotension. Frequent precipitants include gastrointestinal bleeding, sepsis, aggressive diuresis, and paracentesis. However, many patients develop hepatorenal syndrome as a consequence of chronic end-stage liver disease without any identifiable precipitating factors.

A. Incidence

Hepatorenal syndrome develops in 5% of patients with chronic liver disease who present with upper gastrointestinal bleeding, 30% of patients admitted with spontaneous bacterial peritonitis, 10% of patients with ascites treated with total paracentesis, and 25% of patients with severe alcoholic hepatitis. The probability of hepatorenal syndrome developing in a patient with cirrhosis and new onset of ascites is 7–10%. The 5-year probability of hepatorenal syndrome developing in a patient with cirrhosis and recurrent ascites is 40%.

B. Definition

1. Type 1 hepatorenal syndrome

Type 1 is characterized by rapid and progressive impairment of renal function defined by a doubling of the initial serum creatinine to a level higher than 2.5 mg/dL or a 50% reduction of the initial 24-hour creatinine clearance to a level lower than 20 mL/min in less than 2 weeks.

2. Type 2 hepatorenal syndrome

Type 2 is defined as impairment in renal function (serum creatinine >1.5 mg/dL) that does not meet the criteria for type 1. Prerenal failure is a preischemic state and may lead to ischemic tubular necrosis.

In patients with cirrhosis and ascites there is activation of the renin-angiotensin and sympathetic nervous systems, resulting in elevated levels of renin, aldosterone, and norepinephrine. If cirrhotic patients undergo diuresis successfully, the levels of renin, aldosterone, norepinephrine, and antidiuretic hormone all decrease. However, in patients with end-stage liver disease complicated by hepatorenal syndrome, levels of renin, aldosterone, antidiuretic hormone, and norepinephrine are raised and remain persistently elevated despite vigorous attempts at volume expansion. This consequence occurs in part because of decreased systemic vascular resistance and splanchnic arteriolar vasodilation. The splanchnic vasodilation results from increased nitric oxide synthesis. The combination of decreased systemic vascular resistance and arterial underfilling leads to the stimulation of systemic vasoconstrictors which, in turn, causes renal vasoconstriction.

In the early stages of cirrhosis, increased systemic and local vasodilators may act to preserve renal function. The vasodilators include prostacyclin, prostaglandin E₂, nitric oxide, atrial natriuretic peptide, and the kallikrein-kinin system. Vasoconstrictors include angiotensin II, nor-epinephrine, neuropeptide Y, endothelin-1, adenosine, thromboxane A₂, cysteinyl leukotrienes, and F₂-isoprostanes. With the development of hepatorenal syndrome, there is decreased production of local vasodilators and increased production of vasoconstrictors. The net result is intense renal vasoconstriction affecting primarily the renal cortex. NSAIDs, and aspirin, by virtue of their inhibition of prostaglandin synthesis, may actually interfere with the production of local vasodilators in the kidney and can trigger or precipitate an episode of hepatorenal syndrome in cirrhotic patients with marginal renal function.

The major and minor criteria for diagnosis of hepatorenal syndrome are summarized in Table 47–1. Hepatorenal syndrome is characterized by oliguria (<500 mL/24 h), an unremarkable urinary sediment, a low rate of sodium secretion (<10 mEq/L), a low urine output in the absence of diuretics, and a progressive rise of plasma creatinine.