Definition - Development of renal failure in patients with severe liver disease (acute or chronic)
- In the absence of any other identifiable cause of renal pathology
Risk Factors - Strong
- Advanced cirrhosis
- Ascites
- Alcoholic hepatitis
- Acute liver failure
- Hyponatraemia
- High plasma renin activity (PRA)
- Spontaneous bacterial peritonitis
- Weak
- Large volume paracentesis
- GI bleeding
Differential diagnosis Epidemiology - The probability of developing HRS in patients with cirrhosis is approximately 40% in 5 years
- It occurs in 4% of patients admitted with decompensated cirrhosis
Aetiology - HRS may develop spontaneously in patients with cirrhosis
- No objective criteria for a precipitating event other than progressive liver failure
- May also develop in other chronic liver diseases associated with severe liver failure and portal hypertension
- Alcoholic hepatitis
- Acute liver failure
- Cirrhosis is most commonly a result of infectious hepatitis or chronic alcoholism
- Independent predictive factors of HRS occurrence are:
- Low serum sodium concentration
- High plasma renin activity
Clinical features - Key features:
- Advanced cirrhosis (common)
- Jaundice (common)
- Ascites (common)
- Other diagnostic factors
- Moderate lowering of BP (common)
- Peripheral oedema (common)
- Hepatosplenomegaly (common)
- Spider angioma (common)
- Oliguria (uncommon)
- Bruising (uncommon)
- Petechiae (uncommon)
- Palmar erythema (uncommon)
- Scratch marks (uncommon)
- Gynaecomastia (uncommon)
- Encephalopathy (uncommon)
- Pruritus (uncommon)
- Confusion (uncommon)
- Drowsiness (uncommon)
Pathophysiology - Four primary factors are involved in the pathophysiology of HRS:
- Systemic vasodilation
- Leads to a moderate lowering of blood pressure
- Activation of the sympathetic nervous system
- Leads to renal vasoconstriction and altered renal autoregulation
- Causes renal blood flow to be much more dependent on mean arterial pressure
- Relative impairment of cardiac function
- Although cardiac output may increase, it cannot increase adequately to maintain blood pressure
- In cirrhosis, this is termed cirrhotic cardiomyopathy
- Increased formation of renal vasoconstrictors
- Thromboxane A2, F2-isoprostanes, endothelin-1, cysteinyl-leukotrienes
- Their exact role in the pathogenesis of HRS is unclear
Investigations - Creatinine
- Rapid deterioration in patients with type 1 HRS
- Slower course (deteriorating over several months) in type 2 HRS
- Urea
- May be artificially decreased because of reduced hepatic synthesis of urea
- May be increased if GI haemorrhage
- Electrolytes
- Low sodium due to chronic liver disease
- Potassium increases as renal failure progresses
- FBC
- Anaemia and thrombocytopenia due to chronic liver disease
- An elevated WBC count is suggestive of the presence of an infection
- May be responsible for the worsening renal function
- LFTs
- Transaminases, gamma-GT, and Alk phos may be normal or elevated in chronic liver disease
- Low albumin is an indication of impaired liver function
- Coagulation study
- Indication of impaired liver function
- Diagnostic paracentesis and culture of ascitic fluid
- Elevated WBC suggests spontaneous bacterial peritonitis, which commonly precipitates HRS
- Blood culture
- Positive culture suggests sepsis
- Urinalysis and culture
- Presence of WBC and organisms indicates a possible infective cause of worsening renal function
- Presence of RBC and red cell casts suggests an intrinsic renal cause of the renal failure
- Urinary sodium is low in HRS
- Due to preserved tubular function and activation of sodium-retaining systems
- Should not be used as a major criterion to differentiate between HRS and acute tubular necrosis
- CXR
- CXR is performed to exclude sepsis
Managementa) conservative- Supportive therapy
- Patients should have their fluid status, urine output, and serum electrolytes monitored closely
- In particular, patients should be prevented from developing severe hyponatraemia
- But rapid correction of hyponatraemia is avoided
- May lead to demyelination syndrome and increased ascites formation
- If tense, symptomatic ascites is present, paracentesis may temporarily improve renal function
- If severe electrolyte disturbances, volume overload, or metabolic acidosis is present:
- Patients are considered for continuous haemofiltration
- However, limitations such as hypotension make it difficult in this patient group
- Immunisation with influenza and pneumococcal vaccines is important
- These patients are immunocompromised
b) medical - Terlipressin
- Terlipressin (a vasopressin analogue) plus albumin is the first-line therapeutic approach for type 1 HRS
- It may prolong short-term survival, and reverse type 1 HRS
- Treatment should target a serum creatinine of <133 micromol/L (<1.5 mg/dL)
- Fluid bolus
- If renal failure is due to hypovolaemia, it will improve after fluid bolus
- No improvement will occur in patients with HRS
- Antibiotics
- Broad-spectrum non-nephrotoxic antibiotics such as ceftriaxone should be commenced
- Continue until results of cultures are known
- Negative cultures and persisting renal impairment indicate HRS
- Albumin
- Combined treatment with albumin and antibiotics reduces the incidence of renal impairment and death
- Pentoxifylline
- Improves short-term survival in patients with severe alcoholic hepatitis
- Appears to be related to a decreased risk of developing HRS
- Octreotide + midodrine + albumin
- Midodrine is a vasoconstrictor, while octreotide inhibits release of endogenous vasodilators
- These drugs work synergistically to improve renal haemodynamics
- Usually only used as a bridging therapy until liver transplantation is available
c) surgical- Transjugular intrahepatic portosystemic shunt
- Used in patients without severe liver failure in whom vasoconstrictors have failed to improve renal function
- High serum bilirubin, Childs-Pugh score >12, severe hepatic encephalopathy
- Functions as a side-to-side portocaval shunt and serves to relieve portal hypertension
- Performed under analgesia
- Placement of a self-expandable metal stent between a hepatic vein and the intrahepatic portion of the portal vein
- Uses a transjugular approach
- Usually only used as a bridging therapy until liver transplantation is available
- Liver transplantation
- Liver transplantation is the only definitive treatment of HRS
- The decision for transplantation of a limited resource is complex and involves severity of illness and likely prognosis
- Patients with severe co-morbidities are not candidates for a liver transplant
- e.g. CAD or heart failure, advanced age, alcoholism, and infection
Prognosis - Prognosis for patients with HRS is poor
- Type 1 HRS has a hospital survival of less than 10%, and median survival time is 2 weeks
- Type 2 HRS has a median survival time of around 6 months
- The severity of underlying liver disease is a factor in the ability to recover from the renal failure
- The 1-year survival for type 2 HRS is 38.5%
- In patients with HRS, the 5-year survival following liver transplant is around 60%
- This is significantly lower than in patients without HRS (68%)
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