HEPATORENAL SYNDROME

HEPATORENAL SYNDROME - Michael M. Van Ness, MD
BASICS
DESCRIPTION
• An acute, functional, and progressive reduction in renal blood flow and glomerular filtration rate (GFR) secondary to intense renal cortical vasoconstriction in the setting of decompensated cirrhosis
• Other etiologies for renal failure in cirrhosis must be absent to diagnose hepatorenal syndrome (HRS). HRS may be classified as
- Type I  rapidly progressive decline in GFR (2 weeks)
- Type IInot as rapidly progressive (>2 weeks)
• System(s) Affected: Endocrine/Metabolic; Gastrointestinal; Hemic/Lymphatic/Immunologic; Nervous; Renal/urologic
• Synonym(s): Renal failure of cirrhosis; Functional renal failure of cirrhosis; Hepatic nephropathy; Heyd syndrome; Oliguric renal failure of cirrhosis; Hemodynamic renal failure of cirrhosis
GENERAL PREVENTION
See "Risk Factors."
EPIDEMIOLOGY
• Unknown (clear-cut differentiation between HRS and acute tubular necrosis [ATN] or prerenal state not always made)
- Estimate: 32-41/100 admitted to the hospital for cirrhosis with ascites develop HRS at 2 and 5 years
- 1 other study in patients with cirrhosis and ascites: 18% and 39% (of HRS) at 1 and 5 years
• Predominant age: Usually after 4th decade (increased incidence of alcoholic cirrhosis), but may occur at any age
• Predominant sex: Male > Female (increased incidence and prevalence of alcoholic cirrhosis)
RISK FACTORS
Any reduction of effective blood volume in cirrhosis, including
• Excessive diuresis and GI blood loss (e.g., variceal bleeding)
• Excessive diarrhea (lactulose-induced)
• Bacteremia
• Reduction in venous return with tense ascites
• Vomiting, Gl bleeding
• Protein-calorie malnutrition, especially with alcoholic cirrhosis
Genetics
Not important except as risk for liver disease (e.g., infantile or autosomal recessive polycystic kidney disease or 1-antitrypsin deficiency)
ETIOLOGY
• End-stage liver disease from alcohol or toxins
• Viral hepatitis
• Fulminant hepatic failure
• Malignancy
• Any other injury that leads to cirrhosis (e.g., Schistosoma) with accompanying risk factors
ASSOCIATED CONDITIONS
• See "Etiology" and "Differential Diagnosis"
• Pregnancy may be associated with HRS if liver failure occurs during pregnancy.


DIAGNOSIS
SIGNS AND SYMPTOMS
• Oliguria in the setting of cirrhosis
• Jaundice, ascites, encephalopathy
• GI bleeding
• Poor nutritional status
• Splenomegaly
• Spider angioma
• Peripheral vasodilatation
• Tachycardia and bounding pulse often present with HRS (almost always develop during a hospitalization, not on admission).
TESTS
Lab
• Azotemia in the setting of cirrhosis with appropriate spot urine values (consistent with tubular function)
- Sodium 10 mEq/L (10 mmol/L)
- Fractional excretion of sodium 1%
- Urine/plasma creatinine >30:1
- Osmolality: Mild to moderate reduction in concentrating ability (400-600 mOsm/kg/water)
- All reversible causes should be ruled out (e.g., prerenal azotemia, obstruction)
• Urinalysis: Absence of ATN casts; 500 mg/dL protein
• Lack of improvement in renal function following diuretic withdrawal and expansion of plasma volume with 1.5 L of normal saline
• Minor criteria
- Urine volume 500 mL/d
- Urine red blood cells 50/high-power field
- Serum sodium 130 mcg/L
• Other
- Prolonged prothrombin time
- Decreased serum albumin concentration
- Elevated bilirubin
Imaging
• Renal ultrasound shows normal kidneys without obstruction
• Xenon-133 washout curves show a profound reduction in renal cortical perfusion (historic interest)
• Though experimental presently, renal duplex Doppler ultrasonography appears to have predictive value in separating cirrhotics who will develop HRS from those who will not based on resistive index.
Pathological Findings
• Liver: Cirrhosis or acute fulminant failure
• Kidneys: Would function if transplanted into hosts without liver disease; a functional renal derangement only
DIFFERENTIAL DIAGNOSIS
For abrupt onset of oliguria in cirrhosis
• Volume contraction
• Cardiac failure (possibly alcoholic cardiomyopathy)
• Acute vasomotor nephropathy
• Obstruction
• Interstitial nephritis (drug-induced)
TREATMENT
STABILIZATION
Maintenance of volume status in cirrhosis
GENERAL MEASURES
• Supportive
- Avoid iatrogenic events that precipitate HRS.
- Diagnose and treat correctable causes of azotemia in cirrhosis: Try volume expanders (100 g of albumin in 500 mL of normal saline) possible; maximize left ventricular function if possible; relieve urinary obstruction when present.
• Other
- Large-volume paracentesis
- Dialysis: Indicated only as ancillary support for patients awaiting liver transplant or in patients with acute, potentially reversible liver failure
- Head-out water immersion and LeVeen shunts: Of dubious value
- Acute liver failure with HRS may reverse if the liver regenerates.
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Low-dose dopamine may provide temporary benefit. Not curative or proven in clinical studies
• Avoid NSAIDs, demeclocycline, aminoglycosides, or other nephrotoxins.
• Judicious use of loop diuretics
• Avoid iatrogenic volume contraction in cirrhotic inpatients.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Vasopressin analogues (terlipressin and ornipressin) combined with plasma volume expansion demonstrate some effect on the short-term reversibility of renal dysfunction and may act as a bridge to liver transplantation. Questions over efficacy however.
SURGERY
Liver transplantation when feasible is the only curative treatment. The observed 3-month to estimated 6-month to 1-year survival in patients with transjugular intrahepatic portosystemic stent-shunts is improved. LeVeen shunt may provide similar benefit.
FOLLOW-UP
PROGNOSIS
• Grave without liver transplant in chronic cirrhosis or without regeneration of the liver in acute fulminant failure
• If liver transplantation is performed, actuarial patient survival afterward is lower in patients with preceding HRS.
• The patient may be supported with hemodialysis, continuous arteriovenous hemofiltration, or continuous arteriovenous hemodialysis and transjugular portosystemic stent-shunt prior to organ availability for transplantation.
COMPLICATIONS
Death
REFERENCES
1. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology. 1996;23:164-176.
2. Bateller R, Sort P, Gines P, Arroyo V. Hepatorenal syndrome: Definition, pathophysiology, clinical features and management. Kidney Int. 1998;53 (suppl 66):47-53.
3. Brensing KA, Textor J, Strunk H, et al. Transjugular intrahepatic portosystemic stent-shunt for hepatorenal syndrome. Lancet. 1997;349: 697-698.
4. Celeb H, Dondy E, Celikes H. Renal blood flow detection with Doppler ultrasonography in patients with hepatic cirrhosis. Arch Int Med. 1997;157: 564-566.
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6. Gines P, Arroyo V, Rodes J. Ascites and hepatorenal syndrome: Pathogenesis and treatment strategies. Adv Intern Med. 1998;43:99-143.
7. Roberts LR, Kamath PS. Ascites and hepatorenal syndrome; pathophysiology and management. Mayo Clin Proc. 1996;71:874-881.
8. Sussman NL, Lake JR. Treatment of hepatic failure-1996: Current concepts and progress toward liver dialysis. Am J Kidney Dis. 1996;27:605-621.
9. Van Roey G, Moore K. The hepatorenal syndrome. Pediatr Nephrol. 1996;10:100-107.