Hepatorenal Syndrome

Cirrhosis Evolves Clinically From Compensated to Decompensated Stage

Compensated cirrhosis
Cirrhosis without complications Median survival >12 years

Decompensated cirrhosis
Cirrhosis with complications: ascites (HRS), variceal hemorrhage, jaundice, or encephalopathy Annual rate of decompensation of 4-5% Median survival ~1.5 years

Pathogenesis of Ascites in Cirrhosis

cirrhosis

intrahepatic resistance
Portal hypertension Splanchnic vasodilatation Effective arterial blood volume Activation of neurohumoral systems Sodium retension ascites

Common Pathogenesis in Refractory Ascites, Hyponatremia, and HRS

cirrhosis

intrahepatic resistance
Portal hypertension Splanchnic vasodilatation Effective arterial blood volume Activation of neurohumoral systems Sodium retension ascites Refractory Ascites Water retention Hiponatremia Renal vasoconstriction HRS

Hepatorenal syndrome
Hepatic insufficiency and portal hypertension Low GFR (< 40 ml/min) or creatinine > 1.5 mg/dl No shock, bacterial infection, fluid loss and current or recent treatment with nephrotoxic drugs No sustained improvement after withdrawal of diuretics and infusion of 1.5 liters of saline Proteinuria of < 500 mg/dl and negative renal ultrasound

Hepatorenal syndromeAdditional Criteria

Urine volume < 500 ml/d Urine sodium < 10 meq/L Urine osmolality > plasma Urine RBCs < 50/hpf Serum sodium < 130 meq/L

Hepatorenal syndrome
Type 1-Doubling of serum creatinine to > 2.5 mg/dl in less than 2 weeks.
Type 2-Moderate but steady decrease in renal function to creatinine > 2.5 mg/dl.

Who Develops HRS?

Cirrhotic patients with ascites
May be preceded by precipitating factor
Spontaneous bacterial peritonitis (SBP) Sepsis Total paracentesis Upper GI hemorrhage

Patients with acute alcoholic hepatitis Patients with acute liver failure

Treatment of HRS General Measures

Stop all diuretics Look for nephrotoxic drugs Examine urine for white cells and casts Perform renal ultrasound Give 1.5 liters saline/albumin Treat infection

Pharmacologic Therapy

Vasoconstrictors Plus Albumin for HRS

cirrhosis

intrahepatic resistance
Portal hypertension Splanchnic vasodilatation Effective arterial blood volume Activation of neurohumoral systems Renal vasoconstriction HRS

vasoconstrictors
+ Albumin

Terlipressin
Synthetic 12-aminoacid peptide Pro-drug, with pharmacologic activityof its own Constrictive activity via V1-receptors
vascular & extravascular smooth muscle cells

Splanchnic vasoconstriction
portal flow portal pressure

Systemic vasoconstriction
effective blood volume renin and angiotensin

renal vasodilatation improvement in serum creatinine