HEPATORENAL SYNDROME

Definition: clinical condition in pts with chronic liver disease, advanced hepatic failure, and portal HTN characterized by impaired renal function and marked abnormalities in arterial circulation and activity of endogenous vasoactive systems. Marked renal vasoconstriction results in low GFR. Extrarenal arteriolar vasodilation results in reduced total SVR and hypotension. This may occur with any form of chronic or acute hepatic failure.

Pathogenesis: incompletely understood, 2 main theories

1. Direct liver kidney relationship- decreased synthesis/release of a liver-borne renal vasodilator, hepatorenal reflex.

2. Arterial vasodilation hypothesis- extreme arteriolar vasodilation, mostly in the splanchnic circulation results in progressive baroreceptor-mediated activation of vasocontrictor factors (renin-angiotensin, AVP, sympathetic NS, endothelin). HRS results when intrarenal vasodilator mechanisms can no longer compensate.

3. Risk factors for HRS- marked Na and water retention (low urine Na excretion, hyponatremia), low arterial pressure w/ associated vasoconstrictor activity.

4. Precipitants- bacterial infection, GI hemorrhage, paracentesis w/o volume expansion, major surgery.

Diagnosis: International ascites club criteria, only major criteria are required for dx

Major criteria

1. Low GFR, indicated by Cr > 1.5mg/dL, 24hr Cr clearance < 40mL/min

2. NO shock, bacterial infection, fluid loss, nephrotoxic drugs

3. NO sustained improvement in renal function after D/C diuretics and 1.5L volume challenge

4. Proteinuria < 500mL/day

Additional criteria

1. U/O < 500mL/d

2. U Na < 10mEq/L

3. U osm > P osm

4. U RBC < 50/hpf

5. Serum Na < 130mEq/L

Clinical features:

Type I

1. Rapid progressive increase in BUN and Cr over days/wks, progressive decrease in U/O, marked Na retention, hyponatremia

2. Median survival < 2wks

Type II

1. Moderate, stable reduction in GFR (BUN < 50, Cr < 2)

2. Results in diuretic resistant ascites

3. Median survival several months

Treatment:

1. Prevention: NO NSAIDS, albumin for large-volume paracentesis, SBP prophylaxis

2. Renal vasodilators: misoprostol, DA NOT effective, ?endothelin receptor blockers

3. Vasoconstrictors: ?ornipressin/albumin

4. Peritoneovenous shunt: limited anecdotal evidence to support

5. Portosystemic shunt (TIPS): limited evidence for pts ineligible for Tx, ?bridge to Tx

6. Dialysis: may have role as bridge to Tx

7. Liver Tx: persistent moderate renal insufficiency, 1-7% progress to renal failure. Nevertheless, overall 3-yr survival is comparable to non-HRS Tx.

Bataller. Gines. Arroyo. Kidney International. 53(66): S-47-S-53, 1998

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