CLDF #1

Expert Perspectives from the Chronic Liver Disease Foundation (CLDF) on the 2021 American Association for the Study of Liver Diseases (AASLD) Cirrhosis Guidance

Hepatorenal Syndrome

Scroll through this summary or click the button to go through the full diagnostic algorithm.

Download the guidelines in PDF.

Step-by-Step View

QUICK TIP! Hold CTRL+F (PC) or Command+F (Mac) to search for keywords on this page.

QUICK TIP! Hold Tap (3 vertical dots. (Android) or Start typing in the URL field (iPhone) to search for keywords on this page.

Introduction

The “Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases” is a comprehensive guidance on the diagnosis, evaluation, and management of the aforementioned complications of cirrhosis. It serves to replace the prior by the American Association for the Study of Liver Diseases (AASLD) guidelines on the same topics published in 2012. The Chronic Liver Disease Foundation (CLDF) is a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease. Members of the CLDF cirrhosis committee, actively involved in the management and treatment of patients with advanced liver disease, cirrhosis, and its complications, have provided their expert perspectives on this updated guidance. The result is this summary, which provides a streamlined version of the practical recommendations set forth in the guidance to facilitate their use in clinical practice.

Cirrhosis directly results in the development of splanchnic vasodilation, portal hypertension, and bacterial translocation. Specifically, splanchnic vasodilation leads to effective arterial underfilling associated with the activation of vasoconstrictor (e.g., renin-angiotensin) and antidiuretic (e.g., arginine vasopressin) factors. Both portal hypertension (because of increased sinusoidal) and bacterial translocation (because of gut permeability) contribute to the pathogenesis of complications associated with ascites, including hyponatremia, acute kidney injury, hepatorenal syndrome, and spontaneous bacterial infections.

Hepatorenal Syndrome

Defining hepatorenal syndrome (HRS)-Acute kidney injury (AKI)

Acute kidney injury (AKI) is diagnosed by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL within 48 hours or a ≥ 50% increase in SCr that is known or presumed to have occurred within the preceding 7 days. AKI in cirrhosis is mainly caused by prerenal AKI or acute tubular necrosis (ATN). The two main causes of prerenal AKI are hypovolemia and hepatorenal syndrome (HRS).

AKI, acute kidney injury; ATN, acute tubular necrosis; HRS, hepatorenal syndrome

AKI commonly occurs in cirrhosis, and its causes must be evaluated before HRS is diagnosed. AKI must be differentiated from HRS. HRS, a type of AKI known as HRS-AKI under the current terminology, is unique to patients with cirrhosis and occurs in the absence of hypovolemia or significant abnormalities in kidney histology. HRS almost always occurs in patients with cirrhosis who also have ascites and hyponatremia, not compensated disease. Before the development of the new AKI criteria, patients with HRS were classified according to two clinical patterns. The first pattern, known as type-1 HRS, defined by an abrupt decline in kidney function, falls under the current criteria of AKI (100% increase in SCr to a value greater than 2.5 mg/dL). The second pattern, previously known as type-2 HRS, falls into the current definition of chronic kidney disease.

Criteria

New classification

Old classification

HRS-1

Absolute increase in sCr ≥ 0.3 mg/dL within 48 h AND/OR
Urinary output ≤ 0.5 mL/kg body weight ≥ 6 h OR
Percent increase in SCr ≥ 50% using the last available value of outpatient SCr within 3 months as the baseline value

HRS-AKI

HRS-2

HRS-CKD

eGFR < 60 mL/min per 1.73 m² for ≥ 3 months in the absence of other (structural) causes

HRS-2

HRS-AKD

eFGR <60 ml/min per 1.73 m² for > 3 months in the absence of other (structural) OR
Percent increase in SCr < 50% using the last available value of outpatient SCr within 3 months as the baseline value

HRS, hepatorenal syndrome; HRS-AKI, acute kidney injury type of HRS; HRS-NAKI, non-acute kidney injury type of HRS; HRS-AKD, HRS acute kidney disease; HRS-CKD, HRS chronic kidney disease

Streamlining the Diagnostic Algorithm

AIN, acute interstitial nephritis; ATN, acute tubular necrosis; UTI, urinary tract infection; UTO, urinary tract obstruction

Acute rise in SCr is detected: Per the definition of AKI, an increase in SCr ≥ 0.3 mg/dL within 48 hours or a ≥ 50% increase in SCr that is known or presumed to have occurred within the preceding 7 days should lead to suspicion of AKI.

Clinical assessment and serum and urine tests: Assess for the following:

Serum tests

Elevations seen in hemoglobin/hematocrit, total protein/albumin, calcium bicarbonate, or uric acid

Urine tests

Decreased urine volume (< 500 mL/day), urine specific gravity > 1.105, urine sodium < 20 mEq/L, fractional excretion of Na < 1%, fractional excretion of urea < 35%*, or fractional excretion of uric acid < 10%*

*Not affected by diuretic use; Na, sodium

If a specific diagnosis is made other than AKI (e.g., ATN, acute interstitial nephritis [AIN], urinary tract infection [UTI], urinary tract obstruction [UTO]), individualized nephrology care is recommended.

If other diagnoses are ruled out and AKI is confirmed, assess for doubling of SCr:

AKI, acute kidney injury; AIN, acute interstitial nephritis; ATN, acute tubular necrosis; UTI, urinary tract infection; UTO, urinary tract obstruction

If the SCr has not doubled, manage as AKI Stage 1.
If the SCr has doubled, manage as AKI Stage 2 or 3.

AKI Stage

Description

1

Increase in creatinine ≥ 0.3 mg/dL up to 2-fold of baseline

2

Increase in creatinine between 20-fold and 3-fold of baseline

3

Increase in creatinine > 3-fold of baseline of creatinine > 4 mg/dL (353.6 μmol/L) with an acute increase of ≥ 0.3 mg/dL (26.5 μmol/L) or the initiation of RRT, renal replacement therapy

Managing AKI Stage 1

Although there is no specific therapy to reverse AKI, a diligent search must be conducted for treatable causes.

AKI, acute kidney injury; HRS, hepatorenal syndrome

Clinical Reprint

The Current Management of Hepatorenal Syndrome -
Acute Kidney Injury in the United States
and the Potential of Terlipressin

HRS Educational Meetings

New Advances in HRS/AKI
(Request a Live CME Meeting)

HRS Slide Set

Expert Perspectives on the
Management of HRS

AKI, acute kidney injury; HRS, hepatorenal syndrome

If AKI stage 1 is diagnosed, implement risk factor management, which includes the following:

AKI Risk Factor Management

Withdrawal of nephrotoxic drugs

Reduction of withdrawal of diuretics

Detection and treatment of infections

Volume replacement (if severely volume depleted) initially using 25% salt-poor albumin of crystalloids, preferentially balanced

Assess for one of the following scenarios:

SCr normalizes with risk factor management: Continue to monitor.
SCr does not normalize within 1 to 2 days, despite risk factor management: Implement the albumin challenge (albumin 1g/kg for 2 days).
Absolute SCr > 1.5 mg/dL should expedite the use of vasoconstrictors.

If there is no resolution following the albumin challenge, refer to the HRS-AKI criteria below to diagnose HRS-AKI:

Cirrhosis with ascites

AKI according to the International Club of Ascites-Acute Kidney Injury^† criteria‍

No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin infusion (1 g/kg body weight per day)

Absence of shock

No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, or iodinated contrast media)

No signs of structural kidney injury, as indicated by proteinuria (> 500 mg per day), microhematuria (> 50 red blood cells per high-power field), and/or abnormal renal ultrasonography

AKI, acute kidney injury; NSAIDs, nonsteroid anti-inflammatory drugs
^†Increase in SCr ≥ 0.3 mg/dL from the baseline within 48 h or a percent increase in SCr of ≥ 50%, which is known or presumed to have occurred within the preceding 7 days

Managing AKI Stages 2 or 3

AKI, acute kidney injury; HRS, hepatorenal syndrome

If AKI Stage 2 or 3 is diagnosed: Implement risk factor management if applicable
AND
implement the albumin challenge (albumin 1g/kg for 2 days).
Assess for one of the following scenarios:

SCr normalizes: Continue to monitor.
There is no resolution following the albumin challenge: Refer to the below HRS criteria to diagnose HRS.

Cirrhosis with ascites

AKI according to the International Club of Ascites-Acute Kidney Injury^† criteria‍

No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin infusion (1 g/kg body weight per day)

Absence of shock

No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, or iodinated contrast media)

No signs of structural kidney injury, as indicated by proteinuria (> 500 mg per day), microhematuria (> 50 red blood cells per high-power field), and/or abnormal renal ultrasonography

^†Increase in SCr ≥ 0.3 mg/dL from the baseline within 48 h or a percent increase in SCr of ≥ 50%, which is known or presumed to have occurred within the preceding 7 days
AKI, acute kidney injury; NSAIDs, nonsteroid anti-inflammatory drugs

Treating HRS-AKI

HRS, hepatorenal syndrome

Vasoconstrictors, in combination with albumin, are effective in improving kidney function in patients with HRS-AKI. The vasoconstrictor of choice for HRS-AKI is terlipressin. In settings where terlipressin is not available, norepinephrine should be considered, typically in an intensive care setting. If neither can be administered, a trial of oral midodrine in combination with octreotide may be considered, but its efficacy is low. All vasoconstrictors should be dosed according to the table; albumin 25% should be administered in combination with each vasoconstrictor and dosed according to clinical parameters. Response to vasoconstrictor therapy is defined by SCr decreasing to < 1.5 mg/dL or returning to within 0.3 mg/dL of baseline over a maximum of 14 days. In patients whose SCr remains at or above the pretreatment level over 4 days with the maximum tolerated doses of the vasoconstrictor, therapy may be discontinued. Disease may recur after discontinuation of treatment, so close follow-up is warranted. If there is recurrence, patients should be retreated.

Patients with HRS-AKI have a better response to therapy if therapy is started earlier rather than later. Terlipressin, when available, should be considered the treatment of choice as response rates are better than the poor response rates of midodrine, octreotide, and albumin.

Drug

Dosing and Administration

Terlipressin

Vasoconstrictor of choice for treating HRS-AKI

Norepinephrine

Continuous IV infusion starting at 0.5 mg/h to achieve an increase in mean arterial pressure of at least 10 mmHg or an increase in urine output of > 200 mL/4 h

If at least one of these goals is not achieved, increase every 4 h in increments of 0.5 mg/h up to a maximum of 3 mg/h

Oral midodrine in combination with octreotide

Midodrine 5-15 mg po every 8 h
Octreotide 100-200 µg every 8 h or 50 µg/h via IV

AKI, acute kidney injury; HRS, hepatorenal syndrome

Patients on vasoconstrictors and albumin should be closely monitored for the possible development of adverse effects. Adverse effects are infrequent, are mainly related to vasoconstrictors, and include hypertension, peripheral ischemia, abdominal pain, nausea, diarrhea, headache, intestinal ischemia, and cardiac ischemia. Pulmonary edema may develop from fluid overload related to albumin infusion. Early intervention may prevent more serious consequences, and most resolve after dose reduction or discontinuation of therapy.

Additional Special Considerations in HRS Management

Transplantation

All patients with cirrhosis and AKI should be considered for urgent liver transplant (LT) evaluation given the high short-term mortality even in responders to vasoconstrictors.
Simultaneous liver-kidney transplantation may be necessary for patients who are not expected to recover kidney function following transplantation.

Renal Replacement Therapy (RRT)

Use RRT in candidates for LT with worsening renal function, electrolyte disturbances, or increasing volume overload unresponsive to vasoconstrictor therapy.

Initiation of RRT in patients who are not candidates for LT must be made after defining goals of care with the patient and their family.

Multidisciplinary Teams

Given the complexity of cases of patients with suspected HRS-AKI, decisions about management should be made by multidisciplinary teams.

Teams should include specialists in hepatology, nephrology, critical care, and transplant surgery.

AKI, acute kidney injury; HRS, hepatorenal syndrome

The Chronic Liver Disease Foundation is a non-profit organization with content developed specifically for healthcare professionals.© Copyright 2012-2022 Chronic Liver Disease Foundation. All rights reserved. This site is maintained as an educational resource for US healthcare providers only.Use of this Web site is governed by the Chronic Liver Disease Foundation and .

Introduction

Hepatorenal Syndrome

Defining hepatorenal syndrome (HRS)-Acute kidney injury (AKI)

Clinical Insights

Find an Expert

Pharmacoeconomics

More Resources

Streamlining the Diagnostic Algorithm