What are the diagnostic criteria for Hepatorenal Syndrome (HRS)?

From the Guidelines

Hepatorenal syndrome (HRS) is diagnosed using specific criteria that help distinguish it from other causes of kidney injury in patients with advanced liver disease, including the presence of cirrhosis with ascites, acute kidney injury (defined as a serum creatinine increase of ≥0.3 mg/dL within 48 hours or ≥50% from baseline), and the exclusion of other causes of kidney dysfunction, as outlined in the most recent guidelines 1. The diagnosis of HRS requires a comprehensive approach, considering the following key points:

• Presence of cirrhosis with ascites
• Acute kidney injury, defined as a serum creatinine increase of ≥0.3 mg/dL within 48 hours or ≥50% from baseline
• Absence of response to volume expansion with albumin (typically 1 g/kg/day up to 100 g/day for 2 days)
• Absence of shock
• No recent use of nephrotoxic drugs
• No evidence of parenchymal kidney disease (as indicated by significant proteinuria >500 mg/day, microhematuria >50 RBCs per high power field, or abnormal kidney ultrasound) HRS is further classified into two types: HRS-AKI (acute kidney injury) and HRS-NAKI (non-acute kidney injury), with HRS-AKI characterized by a rapid reduction in renal function, and HRS-NAKI representing a more gradual decline in kidney function 1. The pathophysiology of HRS involves intense renal vasoconstriction due to splanchnic vasodilation and reduced effective arterial blood volume, leading to activation of vasoconstrictor systems, and early diagnosis is crucial as HRS carries high mortality 1. The most effective treatment for HRS-AKI includes the use of vasoactive drugs (terlipressin, norepinephrine, or combination of octreotide/midodrine) combined with albumin, which can improve outcomes while patients await definitive treatment with liver transplantation 1. Key considerations in the management of HRS include:
• Use of IV albumin as the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI
• Tailoring volume replacement with albumin to the volume status of the patient
• Avoiding routine administration of a fixed albumin dose in any patient with AKI to prevent volume overload and complications
• Using vasoactive drugs (terlipressin, NE, or combination of octreotide/midodrine) in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis 1.

From the Research

Diagnosis of Hepatorenal Syndrome

The diagnosis of hepatorenal syndrome (HRS) is based on an exclusion-based approach using serum creatinine as a biomarker 2. The International Ascites Club has recommended strict diagnostic criteria for HRS, which include:

• Cirrhosis with ascites
• Serum creatinine > 1.5 mg/dL
• No improvement in serum creatinine after diuretic withdrawal and volume expansion with albumin
• Absence of shock, infection, or other causes of renal dysfunction Some studies have suggested that the use of urine biomarkers and novel plasma expanders may improve the diagnosis and management of HRS 2, 3.

Diagnostic Criteria

The diagnostic criteria for HRS can be divided into two types:

• Type 1 HRS (HRS-AKI): characterized by a rapid deterioration of renal function, with a doubling of serum creatinine in less than 2 weeks 3, 4
• Type 2 HRS (HRS-CKD): characterized by a more gradual deterioration of renal function, with a serum creatinine > 1.5 mg/dL for more than 2 weeks 4 In some cases, the diagnostic criteria for HRS may not be completely fulfilled, and the diagnosis may be presumed based on clinical judgment 5.

Limitations of Diagnostic Criteria

The current diagnostic criteria for HRS have some limitations, including:

• The use of serum creatinine as a biomarker, which may not accurately reflect renal function in all patients 2
• The need for a sustained period of time to measure serum creatinine, which may delay treatment 2
• The absence of a clear definition of HRS in patients with underlying chronic kidney disease or other renal disorders 4

Future Directions

Future studies are needed to develop new biomarkers and diagnostic criteria for HRS, and to improve the management and outcomes of patients with this condition 2, 3. The use of biomarkers, metabolomics, and other novel approaches may help to identify patients at risk of HRS and allow for earlier diagnosis and treatment 3.