SIGNS AND SYMPTOMS 
Signs of acute or chronic liver disease:
- Signs of portal hypertension
- Ascites, often tense
- Progressive oliguria
- Jaundice or hepatic encephalopathy
- Coagulopathy
- Tachycardia
- Hypotension
- Dyspnea, tachypnea due to tense ascites
History
Acute or chronic hepatic disease with advanced hepatic failure and portal hypertension:
- Worsening liver function often predates acute renal dysfunction
Physical Exam
- Consistent with severe hepatic disease
- Vital signs may show:
- Fever in signs of sepsis
- Hypotension in sepsis, intestinal bleeding, or even a low baseline intrinsic to liver disease
DIAGNOSIS TESTS & INTERPRETATION
Lab
- CBC:
- Electrolytes:
- Glucose
- Elevated BUN, creatinine (Cr):
- Normal Cr found with low GFR) in association with muscle wasting, poor nutrition, and ascites.
- Cr increased by some medications (cimetidine, trimethoprim, and spironolactone) due to inhibition of tubular secretion of Cr.
- Hyperbilirubinemia can create a falsely lower serum Cr.
- PT, PTT
- Urinalysis:
- Spot urine sodium and Cr, and serum and urine osmolality:
- Spot urine Na+ < 10 mEq/L
- Fractional excretion of Na+ < 1%
- Urine/plasma Cr > 30:1
- Hyperosmolar urine > plasma osmolarity
- 24 hr urine output (low in the absence of diuretics)
- 24 hr urine CrCl:
- Blood, ascitic fluid, and urine culture as indicated
- Urinary excretion of β2-microglobulin—useful marker of acute tubular damage
Imaging
- CXR for signs of CHF or fluid overload
- Renal US: Rule out obstructive uropathy:
- Duplex Doppler US can be used to assess degree of renal vasoconstriction.
Diagnostic Procedures/Surgery
- ECG for dysrhythmia or signs of hyperkalemia
- Foley catheter placement to assess for urine output and exclude urinary retention as cause of RF
- Central venous pressure (CVP) measurements may help assess volume status:
- Differentiates prerenal (low) from HRS (elevated)
DIFFERENTIAL DIAGNOSIS
- HRS is diagnosis of exclusion
- Glomerulopathy:
- Hepatitis B can lead to glomerulonephritis
- Hepatitis C can cause intrinsic renal damage due to cryoglobulinemia
- ATN:
- Urine sodium > 30 mEq/L
- Urine osmolality equals plasma osmolality
- Urine casts and cellular debris
- Prerenal azotemia:
- Over diuresis
- GI bleeding
- Urine output improves following correction of hypovolemia
- Obstructive uropathy
- Infections or sepsis
- Medications—NSAIDs
- Interstitial nephritis
- Post liver transplant renal dysfunction due to:
- HRS due to failure of transplanted liver
- Medications (e.g., cyclosporine)
- Pre-existing renal disease
- Perioperative hypovolemia
[Outline]
PRE-HOSPITAL
Attention to ABCs:
- Airway control may be a concern in severe encephalopathy.
- Respiratory failure seen with tense ascites as well as volume overload
- Correction of hypotension and ensure adequate IV access
INITIAL STABILIZATION/THERAPY
- ABCs
- Aggressive correction of hypovolemia with:
- 0.9% NS IV fluid
- Colloid volume expanders: 100 g albumin in 500 mL of NS
- Closely monitor clinical status including use of CVP
- Urine output should improve with correction of prerenal azotemia
- Manage life-threatening emergencies of RF:
ED TREATMENT/PROCEDURES
- Exclude reversible or treatable causes of HRS.
- Supportive care until hepatic function recovers
- Do no harm—discontinue potentially nephrotoxic agents:
- Treat primary disease
- Search for and treat coexisting renal disease
- Correct electrolyte imbalances
- Treat any associated cardiopulmonary disorder and hypoxia
- Initiate broad-spectrum antibiotics if sepsis suspected
- Correct liver-associated complications:
- Obstructive jaundice
- Hepatic encephalopathy
- Hypoglycemia
- Peritonitis
- Consider large-volume paracentesis with IV albumin replacement (to relieve tense ascites):
- Increases renal blood flow
- May briefly improve HRS
- Transhepatic intrahepatic portosystemic shunt (TIPS):
- Promising results, but small studies
- Those who survived the procedure had 40% survival at 12 mo compared to 90% at 3 mo.
- Dialysis:
- Useful in correcting fluid, electrolytes, acid–base imbalances, pulmonary edema
- Indicated for patients who have likelihood of hepatic regeneration, hepatic recovery, or liver transplantation
- Liver transplant:
- Is currently the only definitive therapy
MEDICATION
- No medications are first line and should only be considered after other causes of renal dysfunction excluded
- Dopamine (renal dose): 2–5 µg/kg/min:
- May improve renal function
- Not curative
- Midodrine (7.5–12.5 mg PO TID) and octreotide (100–200 µg SC TID):
- Octreotide is the analog of somatostatin
- Midodrine is a sympathomimetic drug
- Misoprostol: 0.4 mg PO QID:
- Ornipressin:
- Vasopressin analog
- Increases renal perfusion pressure and function
- Not available in US
- Terlipressin: 2 mg/d for 2 days:
- Synthetic analog of vasopressin
- Intrinsic vasoconstrictor activity
- Not available in US
[Outline]
Any degree of renal dysfunction needs to be evaluated very seriously in patients with liver disease.
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- Lata, J. Hepatorenal syndrome. World J Gastroenterol. 2012;18(36):4978–4984.
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- Senzolo M, Cholangitas E, Tibballs J, et al. Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome. Eur J Gastroenterol Hepatol. 2006;18:1143–1150.
- Verna EC, Wagener G. Curr Opin Crit Care. 2013;19(2):133–141.
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