Hepatorenal Syndrome Workup

Updated: Sep 22, 2022
  • Author: Deepika Devuni, MD; Chief Editor: BS Anand, MD  more...
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Workup

Laboratory Studies

Guidelines by the British Society of Gastroenterology (BSG), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD) recommend the use of abdominal ultrasonography, diagnostic paracentesis, and ascitic fluid cultures in the workup of patients with suspected hepatorenal syndrome (HRS). [21]

The diagnosis of HRS is one of exclusion [13] and depends mainly on the serum creatinine level, as no specific tests establish the diagnosis of HRS. Although serum creatinine level is a poor marker of renal function in patients with cirrhosis, no other validated and reliable noninvasive markers exist for monitoring renal function in these patients. [22]

The International Club of Ascites (ICA) proposed revised diagnostic criteria of HRS-acute kidney injury (AKI) (previously HRS type 1) in 2015, including the following [23] :

  • Diagnosis of cirrhosis and ascites
  • Diagnosis of AKI according to ICA-AKI criteria

  • No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin 1 g/kg body weight

  • Absence of shock

  • No current or recent use of nephrotoxic drugs (nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides, iodinated contrast media, etc)

  • No macroscopic signs of structural kidney injury, as defined as an absence of proteinuria (>500 mg/day); absence of microhematuria (>50 red blood cells per high-power field [RBCs/hpf]); normal findings on renal ultrasonography

ICA-AKI criteria

  • Baseline sCr is defined as a value of serum creatinine (sCr) obtained in the previous 3 months or on admission if no baseline is available.

  • AKI is defined as an increase in sCr ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours or a percentage increase in sCr ≥ 50% from baseline which is known, or presumed, to have occurred within the prior 7 days.

The ICA-AKI staging of AKI is as follows:

  • Stage 1: Increase in sCr ≥ 0.3 mg/dL (26.5 µmol/L) or an increase in sCr ≥ 1.5 fold to 2-fold from baseline

  • Stage 2: Increase in sCr > 2 to 3-fold from baseline

  • Stage 3: Increase of sCr > 3-fold from baseline or sCr ≥ 4.0 mg/dL (353.6 µmol/L) with an acute increase ≥ 0.3 mg/dL (26.5 µmol/L) or initation of renal replacement therapy

The revised diagnostic criteria divided AKI in three stages to reflect its association with severity of disease. The HRS-1 diagnostic requirement for sCr to double to a value above 2.5 mg/dL over 2 weeks was removed due to its barrier to clinicians to initiate treatment on time prior to the disease progression to higher stages of AKI. The use of decreased urine output (< 0.5 mL/kg/h for >6 h) as part of the AKI definition for patients with cirrhosis was removed due to several reasons: 1) cirrhotic patients can be and often are oliguric due to sodium retention, but they have preserved renal function, and 2) the urine output may be increased due to use of diuretics and, therefore, urine output collection may be inaccurate. It has been proposed that urine output may be used in the AKI definition only if a urinary catheter is placed for precise measurement.

Response to treatment is defined as the following:

  • No response: No regression of AKI

  • Partial response: Regression of AKI stage with a reduction of sCr to ≥ 0.3 mg/dL (26.5 µmol/L) above the baseline value

  • Full response: Return of sCr to a value within 0.3 mg/dL (26.5 µmol/L) of the baseline value

Complete blood cell count with differential

This may indicate the presence of an underlying infection such as spontaneous bacterial peritonitis (SBP) if leukocytosis or bands are present, a condition known to present with reversible impairment in renal function. However, many patients with SBP do not have serum leukocytosis. Because shock from gastrointestinal bleeding may cause acute tubular necrosis, checking the hematocrit level and platelet count is helpful.

Serum electrolytes and renal function

These are essential investigations to obtain data for diagnosing HRS.

Liver function tests with prothrombin time

Although the degree of liver failure does not correlate with the development of HRS, these investigations are necessary to assess the patients' Child-Pugh scores. [18]

Alpha-fetoprotein levels

Although few studies demonstrate a relationship between hepatoma and the development of HRS, this test should be performed when patients with cirrhosis decompensate.

Blood cultures

Infections place patients at an increased risk for decompensation, and looking for bacteremia, particularly if no precipitant is identified, is prudent. Occasionally, patients may present with culture-negative SBP (20%), and performing blood cultures is wise under these circumstances.

Cryoglobulins

Measuring these may be helpful in patients with hepatitis B and/or C, who can develop renal failure from cryoglobulinemia. Treatment and eradication of the underlying disease, if performed early in the course of the disease process, can reverse renal failure.

Urinalysis and urine electrolytes

Significant proteinuria or hematuria may provide a clue that an organic cause may be responsible for patients' renal failure. Similarly, urinary tract infection may be detected, and this usually is readily treatable.

Measuring urine sodium and creatinine levels is used as a screening test to assess the degree of sodium retention. Patients with low urine sodium excretion (< 5 mEq/L) are at a greater risk of developing HRS. Urine sodium and creatinine levels are also used to calculate the fractional excretion of sodium, which is helpful in differentiating HRS and prerenal azotemia from intrinsic renal disease.

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Imaging Studies

Abdominal ultrasonography

This is a useful noninvasive test to help exclude hydronephrosis and intrinsic renal disease, which may be characterized by bilateral small kidneys. When combined with Doppler studies, valuable information may be provided on renal vascular flow.

Echocardiography

This study may be helpful for evaluating the right ventricular preload, ventricular filling pressures, and cardiac performance in response to fluid replacement.

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Procedures

Paracentesis

Spontaneous bacterial peritonitis (SBP) can present with reversible impairment of renal function, and performing diagnostic paracentesis is strongly recommended in all patients. The role of therapeutic paracentesis/large-volume paracentesis (LVP) in hepatorenal syndrome (HRS) is more controversial in the absence of tense ascites. Concerns exist that further volume depletion may aggravate the renal function, due to third spacing in a patient with a known underlying systemic circulatory disturbance. Albumin replacement is recommended in these patients when LVP is performed. Ten grams of albumin is administered for every liter of ascites drained, to a maximum of 50 g of albumin.

Bladder catheterization

Catheterization may be helpful to exclude urinary retention as a potential cause of acute renal failure in these patients. However, long-term indwelling urinary catheters are not recommended (because of the risk of acquiring urinary tract infection) unless patients are incontinent and are at risk of developing skin breakdown or unless strict recording of urinary output is mandatory.

Central line and Swan-Ganz line placement

Measurement of central venous pressure and pulmonary capillary wedge pressure may be helpful in patients who do not respond to an adequate trial of plasma expansion. Hemodynamic findings in HRS include increased cardiac output, reduced mean arterial pressure (range of 60-80 mm Hg), and reduced total systemic vascular resistance. These findings, although characteristic of patients with cirrhosis, can also be observed in other conditions, such as anaphylaxis and sepsis. Invasive hemodynamic monitoring, aside from the risk of procedure-related complications, also has limitations for assessing volume status in patients. For example, a study by Kumar showed that, in healthy volunteers, neither the central venous pressure nor the pulmonary artery occlusion pressure were useful for predicting ventricular preload with respect to optimizing cardiac performance. [24]

Histologic findings

The kidneys are histologically normal because HRS is a functional disorder.

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