What are the criteria for hepatorenal syndrome (HRS), a type of rapid kidney function decline in patients with advanced liver disease, particularly cirrhosis?

From the Guidelines

Hepatorenal syndrome (HRS) is diagnosed based on specific criteria, including serum creatinine >1.5 mg/dl, absence of shock, absence of hypovolemia, no current or recent treatment with nephrotoxic drugs, and absence of parenchymal renal disease, as defined by proteinuria <0.5 g/day, no microhaematuria, and normal renal ultrasonography 1. The diagnosis of HRS involves a combination of clinical and laboratory findings. Key criteria include:

• Serum creatinine >1.5 mg/dl (133 lmol/L)
• Absence of shock
• Absence of hypovolemia, as defined by no sustained improvement of renal function following at least 2 days of diuretic withdrawal and volume expansion with albumin
• No current or recent treatment with nephrotoxic drugs
• Absence of parenchymal renal disease, as indicated by proteinuria <0.5 g/day, no microhaematuria (<50 red cells/high powered field), and normal renal ultrasonography HRS is further classified into two types: type 1 HRS, characterized by a rapid and progressive impairment in renal function, and type 2 HRS, characterized by a stable or less progressive impairment in renal function 1. The criteria for HRS diagnosis are crucial for prompt recognition and treatment, as HRS carries high mortality, and early treatment with vasoconstrictors, such as terlipressin, plus albumin can improve outcomes while patients await definitive treatment with liver transplantation 1. The management of HRS involves the use of vasoconstrictors, such as terlipressin, and albumin, with the goal of improving renal function and reducing mortality 1. In patients with type 1 HRS, the use of transjugular intrahepatic portosystemic shunts (TIPS) may improve renal function, although its applicability is limited due to the severity of liver failure 1. Renal replacement therapy should be considered in non-responders to vasoconstrictors and in patients with end-stage kidney disease, with indications similar to those in the general population 1.

From the FDA Drug Label

Patients with cirrhosis, ascites, and a diagnosis of HRS-1 with a rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2.25 mg/dL and meeting a trajectory for SCr to double over two weeks, and without sustained improvement in renal function (<20% decrease in SCr and SCr ≥2.25 mg/dL) 48 hours after both diuretic withdrawal and the beginning of plasma volume expansion with albumin were eligible to participate. The criteria for hepatorenal syndrome (HRS) include:

• Cirrhosis and ascites
• Rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2.25 mg/dL
• Meeting a trajectory for SCr to double over two weeks
• No sustained improvement in renal function (<20% decrease in SCr and SCr ≥2.25 mg/dL) 48 hours after:
  • Diuretic withdrawal
  • Plasma volume expansion with albumin 2

From the Research

Definition and Diagnosis of Hepatorenal Syndrome (HRS)

• HRS is a severe complication of cirrhosis that develops in the final phase of the disease, characterized by a rapid reduction of renal function 3.
• Two types of HRS exist: Type 1, defined by a rapid reduction of renal function, and Type 2, with a slowly progressive reduction of renal function 3.
• The International Ascites Club defines HRS by the presence of five criteria:
  • Severe cirrhosis
  • Glomerular hypofiltration
  • No other functional or organic causes
  • Failure of plasma volume expansion
  • No proteinuria 3.
• Type 1 HRS is diagnosed when the serum creatinine level increases by more than 50% of the baseline value to above 133 micromol/L 3.
• The term acute kidney injury (AKI) is now adopted to include all functional and structural forms of acute renal dysfunction in cirrhosis, with various stages describing the severity of the condition 4.

Diagnostic Criteria for HRS

• Significant recent changes in the understanding of the pathophysiology of renal dysfunction in cirrhosis include the role of inflammation in addition to hemodynamic changes 4.
• Albumin is used for its volume expanding and anti-inflammatory properties to confirm the diagnosis of HRS-AKI, which is stage 2 AKI [doubling of baseline serum creatinine (sCr)] while fulfilling all other criteria of HRS1 4.
• Vasoconstrictors are added to albumin as pharmacotherapy to improve the hemodynamics, with terlipressin being the most common vasoconstrictor used worldwide, although not yet available in North America 4.
• Norepinephrine is equally effective as terlipressin in reversing HRS1, and recent data show that norepinephrine may be administered outside the intensive care setting, but close monitoring is still required 4.

Prognostic Factors and Treatment Outcomes

• Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin 5.
• Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001) 5.
• The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%) 5.
• Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04) 5.
• Combined liver and kidney transplantation is recommended for patients with prolonged history of AKI, underlying chronic kidney disease or with hereditary renal conditions 4.