What is the classification of hepatorenal syndrome based on kidney dysfunction severity and other complications?

Classification of Hepatorenal Syndrome

Hepatorenal syndrome is classified into two types based on the acuity and severity of kidney dysfunction: Type 1 HRS (now termed HRS-AKI) characterized by rapid, progressive renal impairment with serum creatinine increasing ≥100% to >2.5 mg/dL in less than 2 weeks, and Type 2 HRS (now termed HRS-CKD) featuring stable or slowly progressive renal dysfunction with a more chronic course. 1, 2

Modern Classification System

The classification has evolved from the traditional Type 1/Type 2 nomenclature to align with contemporary nephrology terminology:

HRS-AKI (formerly Type 1 HRS)

• Rapid progression: Doubling of serum creatinine to >2.5 mg/dL or 50% reduction in creatinine clearance to <20 mL/min within 2 weeks 1, 3
• Acute presentation: Often precipitated by bacterial infections (particularly spontaneous bacterial peritonitis), gastrointestinal bleeding, or large-volume paracentesis without albumin replacement 1, 4
• Poor prognosis: Median survival of approximately 2 weeks without treatment and 1 month overall 1, 5
• Clinical manifestation: Acute kidney injury with rapidly deteriorating renal function 2, 6

HRS-CKD (formerly Type 2 HRS)

• Stable course: Moderate renal dysfunction that is stable or slowly progressive 1, 4
• Chronic presentation: More gradual decline without obvious precipitating events 7, 6
• Better prognosis: Median survival of approximately 6 months 5, 6
• Clinical manifestation: Primarily presents as refractory ascites with chronic kidney dysfunction 5, 3

AKI Staging Within HRS Diagnosis

The International Club of Ascites and AASLD recommend using standardized AKI staging criteria for HRS-AKI 1, 8:

• Stage 1: Creatinine increase ≥0.3 mg/dL or 1.5-2 times baseline 1
• Stage 2: Creatinine increase 2-3 times baseline 1
• Stage 3: Creatinine increase >3 times baseline, or creatinine >4 mg/dL with acute increase ≥0.3 mg/dL, or initiation of renal replacement therapy 1

Critical Evolution in Classification

The fixed threshold of serum creatinine >1.5 mg/dL has been abandoned because it delays diagnosis and treatment. 1 The newer criteria emphasize dynamic changes in creatinine rather than absolute values, allowing earlier detection when outcomes are better 1. The old requirement for creatinine to reach 2.5 mg/dL for Type 1 HRS diagnosis has been removed from updated guidelines 1.

Diagnostic Framework

All HRS diagnoses require meeting these core criteria 9, 1, 8:

• Cirrhosis with ascites
• AKI defined by ICA-AKI criteria (for HRS-AKI) or chronic kidney dysfunction (for HRS-CKD)
• No improvement after 2 consecutive days of diuretic withdrawal and albumin expansion (1 g/kg, maximum 100 g/day) 9, 1
• Absence of shock 9, 1
• No current or recent nephrotoxic drug exposure (NSAIDs, aminoglycosides, contrast media) 9, 1
• Absence of structural kidney injury: no proteinuria >500 mg/day, no microhematuria >50 RBCs/HPF, normal renal ultrasonography 9, 1

Important Clinical Distinctions

HRS vs. Other Causes of AKI in Cirrhosis

HRS accounts for only 15-43% of AKI cases in cirrhotic patients 1. Other common causes include:

• Hypovolemia: 27-50% of cases (from diuretics, bleeding, inadequate albumin replacement) 1
• Acute tubular necrosis: 14-35% of cases (from prolonged hypotension, sepsis, nephrotoxins) 1

Biomarkers can help differentiate: Urinary NGAL >220 μg/g creatinine suggests acute tubular necrosis rather than HRS (88% sensitivity, 85% specificity) 8. Other markers include KIM-1, IL-18, and L-FABP 1.

Common Pitfalls to Avoid

• Do not wait for creatinine to reach 1.5 mg/dL or 2.5 mg/dL before diagnosing HRS-AKI—use dynamic AKI criteria instead 1, 8
• Do not rely on urine output as a diagnostic criterion in cirrhotic patients with ascites, as oliguria may reflect appropriate sodium retention rather than kidney injury 1
• Recognize that HRS is not purely functional—severe or repeated episodes can cause structural kidney damage, challenging the traditional view of complete reversibility 1, 4
• Consider renal biopsy if proteinuria, microhematuria, or abnormal kidney size is present to evaluate for parenchymal disease 1

Prognostic Implications by Classification

• HRS-AKI: 28-day mortality of 78% without treatment; requires urgent liver transplant evaluation 9, 1
• HRS-CKD: More favorable short-term prognosis but still indicates advanced liver disease with high mortality without transplantation 5, 6
• Response to vasoconstrictors: Reversal of HRS occurs in 40-76% of patients treated with terlipressin plus albumin, but even responders have poor long-term prognosis without transplantation 8, 5, 6