Author:
Douglas W.Chesson
Matthew T.Keadey
Description
- Renal failure (RF) in patients with acute or chronic liver disease with no other identifiable cause of renal pathology
- Hepatorenal syndrome (HRS) represents significant decline in renal perfusion due to severe liver disease:
- Type I HRS:
- Acute form with spontaneous RF in patients with liver disease
- Rapidly progressive
- 90% mortality within 3 mo
- Seen with acute liver failure or alcoholic hepatitis
- Oliguric or anuric at presentation
- Type II HRS:
- Slow course of RF
- Seen in patients with diuretic resistant ascites
- Lower mortality than type I HRS
- Hallmarks of HRS:
- Patients must have cirrhosis and ascites
- Prerenal disease
- A functional form of acute kidney injury (AKI) due to renal vasoconstriction
- AKI according to International Club of Ascites (ICA) criteria
- Reversible renal vasoconstriction and mild systemic hypotension, but without shock
- Kidneys have normal histology and structure on US
- Lack of improvement in renal function after volume expansion with albumin and diuretic withdrawal for 48 hr
- No current use of nephrotoxic drugs
- Liver disease causes systemic vasodilation with decrease in arterial blood volume:
- Reflex activation of sympathetic nervous system
- Activation of renin-angiotensin-aldosterone system (RAAS)
- Stimulation of numerous vasoactive substances:
- Nitric oxide
- Prostacyclin
- Atrial natriuretic peptide (ANP)
- Arachidonic acid metabolites
- Platelet-activating factor
- Endothelins
- Catecholamines
- Angiotensin II
- Thromboxane
- Action of vasoconstrictors prevails over vasodilator effects:
- Renal hypoperfusion ensues due to renal cortical vasoconstriction
- Decrease in renal blood flow and glomerular filtration rates (GFRs)
- Decreased urine sodium excretion (U Na <10 mEq/d)
- Incidence of HRS:
- 18% at first year, 39% at 5 yr
- Hyponatremia and high plasma renin levels are risk factors
Etiology
- Chronic liver disease, especially alcohol related (cirrhosis, severe alcoholic hepatitis)
- Fulminate hepatic failure
- Precipitating factors:
- Decreased effective blood volume:
- GI bleeding
- Vigorous diuresis
- Large-volume paracentesis
- Use of nephrotoxic agent:
- Sepsis:
- Spontaneous bacterial peritonitis (SBP) leads to a 33% chance of developing RF during that year
- SBP prophylaxis reduces the chance of developing acute RF
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
Diagnostic Tests & Interpretation
Lab
- CBC:
- Electrolytes:
- Glucose
- Elevated BUN, creatinine (Cr):
- ICA criteria: Increase in Cr ≥0.3 mg/dL within 48 hr or increase in Cr ≥50% from baseline in the last 7 d
- Normal Cr found with low GFR in association with muscle wasting, poor nutrition, and ascites in cirrhosis
- 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 in cirrhotic patients
- 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
Prehospital
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 expand ers: Albumin (1 g/kg)
- Closely monitor clinical status including use of CVP
- Urine output should improve with correction of prerenal azotemia
- Manage life-threatening emergencies of RF:
- Hyperkalemia
- Severe acidosis
- Hypoxemia
- Uremic pericarditis
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):
- Limited data to suggest clinical usage
- 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
- May consider liver support with molecular absorbent recirculating system (MARS) while awaiting transplant
Medication
- No medications are first line and should only be considered after other causes of renal dysfunction excluded
- Dopamine (renal dose): 2-5 mcg/kg/min:
- May improve renal function
- Not currently recommended
- Midodrine (7.5-12.5 mg PO t.i.d) and octreotide (100-200 mcg SC t.i.d):
- Octreotide is the analog of somatostatin
- Midodrine is a sympathomimetic drug
- Norepinephrine:
- Use through central line in ICU setting
- Peripheral vasoconstrictor acting at α-receptors
- Misoprostol: 0.4 mg PO q.i.d:
- Ornipressin:
- Vasopressin analog
- Increases renal perfusion pressure and function
- Not available in US
- Terlipressin: 2 mg/d for 2 d:
- Synthetic analog of vasopressin
- Effective in reversing HRS in 40-50% of patients
- Intrinsic vasoconstrictor activity
- Not available in the U.S.
- AcevedoJ, CrampM. Hepatorenal syndrome: Update on diagnosis and therapy . World J Hepatol. 2017;9(6):293-299.
- ChanS, AuK, FrancisR, et al. An update on hepatorenal syndrome . J Renal Hepatic Disorders. 2017;1:1-13.
- GinesP, GuevaraM, ArroyoV, et al. Hepatorenal syndrome . Lancet. 2003;362(9398):1819-1827.
- LataJ. Hepatorenal syndrome . World J Gastroenterol. 2012;18(36):4978-4984.
- NadimMK, KellumJA, DavenportA, et al. Hepatorenal syndrome: The 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group . Crit Care. 2012;16(1):R23.
- RobertsLR, KamathPS. Ascites and hepatorenal syndrome: Pathophysiology and management . Mayo Clin Proc. 1996;71(9):874-881.
- SenzoloM, CholangitasE, TibballsJ, et al. Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome . Eur J Gastroenterol Hepatol. 2006;18(11):1143-1150.
- VernaEC, WagenerG. Renal interactions in liver dysfunction and failure . Curr Opin Crit Care. 2013;19(2):133-141.
- WongF, BlendisL. New challenge of hepatorenal syndrome: Prevention and treatment . Hepatology. 2001;34(6):1242-1251.
See Also (Topic, Algorithm, Electronic Media Element)
The authors gratefully acknowledge Richard McCormick for his contribution to the previous edition of this chapter.