Definition

A clinical condition which occurs predominantly in patients with chronic liver disease, advanced hepatic failure and portal hypertension. It is characterised by impaired renal function and marked abnormalities in the arterial circulation and activity of the endogenous vasoactive systems in the kidney. In the kidney there is marked renal vasoconstriction which results in a low GFR. In the extrarenal circulation arteriolar vasodilatation predominates resulting in reduced systemic vascular resistance and arterial hypotension.

Although hepatorenal syndrome is more common in patients with advanced cirrhosis it may develop in patients with other chronic or acute liver diseases

Pathogenesis

Unclear
renal failure probably functional. Pathological abnormalities are minimal and not consistently present
functional integrity of renal tubules is maintained during renal failure, as manifested by relatively normal capacity for both sodium reabsorption and urine concentration
kidneys from patients with hepatorenal syndrome function normally after they are transplanted into patients with normal liver function and renal function recovers when a patient with hepatorenal function undergoes successful liver transplantation
although renal hypoperfusion with preferential renal cortical ischaemia underlies the renal failure in hepatorenal syndrome the factors responsible for the sustained reduction in cortical perfusion and suppression of filtration have not been fully elucidated. Currently thought to be due to an imbalance of renal vasodilators (eg prostaglandins, NO) and vasocontrictors (eg renin-angiotensin system, sympathetic nervous system, endothelin, leukotrienes).
whether the renal hypoperfusion is due to systemic circulatory changes or is merely accompanied by these changes is not clear

Types

Type I

rapid and progressive increase in urea and creatinine over days or weeks
renal failure often associated with progressive reduction in urine volume, marked sodium retention, and hyponatraemia
hyperkalaemia frequent
metabolic acidosis uncommon
patients usually severely ill with signs of advanced liver failure eg jaundice, encephalopathy, coagulopathy
common in alcoholic cirrhosis with associated alcoholic hepatitis
precipitant in approximately 50%:
bacterial infection, especially spontaneous bacterial peritonitis
GI haemorrhage
paracentesis without plasma expansion
major surgery
median survival time <2 weeks

Type II

moderate and stable reduction of GFR
usually occurs in patients with relatively preserved hepatic function
main clinical consequence is diuretic resistant ascites

Diagnosis

Major criteria

low GFR as indicated by serum creatinine >140 m mol/l or creatinine clearance <40 ml/min
absence of shock, ongoing bacterial infection, fluid losses and current treatment with nephrotoxic drugs
no sustained improvement in renal function (decrease in creatinine to 140 m mol/l or creatinine clearance to 40 ml/min) following diuretic withdrawal and expansion of plasma volume with 1.5l of plasma expander
proteinuria <500 mg/day and no ultrasound evidence of obstructive uropathy or parenchymal renal disease

Associated features

urine volume <500 ml/day
urine Na <10 mmol/l
urine osmolality >plasma
urine RBCs <50 per high power field
serum Na <130 mmol/l

Treatment

exclude prerenal renal failure and ATN
haemodialysis, renal vasodilators, prostaglandin excretion modifiers, insertion of peritoneovenous shunts and TIPS have all been tried but do not improve survival
terlipressin may reduce mortality and improve renal function
uncontrolled studies suggest that the combination of furosemide, albumin and noradrenaline may improve renal function in type I hepatorenal syndrome
in carefully selected patients liver transplantation improves survival