Hepatorenal syndrome

Definition

Hepatorenal syndrome (HRS) is a functional, potentially reversible renal dysfunction in advanced liver cirrhosis with ascites or in alcoholic steatohepatitis. Structural kidney damage is typically absent; the cause is markedly reduced renal perfusion.

Classification

• HRS type 1 (historical term): rapidly progressive kidney failure; in the classic definition, doubling of serum creatinine to above 2.5 mg/dL within less than two weeks
• HRS type 2 (historical term): moderate, stable or slowly progressive renal dysfunction with creatinine of 1.5–2.5 mg/dL, often together with ascites that is difficult to control

According to the consensus of the International Club of Ascites (ICA) and ADQI (2024), these terms are replaced by HRS-AKI (acute kidney injury), HRS-AKD (kidney dysfunction for less than 90 days without meeting AKI criteria) and HRS-CKD (more than 90 days).

Aetiopathogenesis

The starting point is arterial splanchnic vasodilatation in portal hypertension. The effective arterial blood volume falls, and the renin-angiotensin-aldosterone system, the sympathetic nervous system and vasopressin (ADH) are activated in response. Sodium and water retention promote ascites and hyponatremia. The result is severe renal vasoconstriction with a fall in glomerular filtration rate.

HRS is frequently triggered by an event that further impairs the circulation, such as a bacterial infection (especially spontaneous bacterial peritonitis), gastrointestinal bleeding or marked fluid loss.

Clinical features

HRS usually occurs in patients with advanced cirrhosis and ascites or with alcoholic hepatitis. It is characterised by increasing oliguria and a rise in nitrogenous waste products without structural kidney damage. Hyponatremia, ascites that is difficult to control and other signs of decompensation are often present.

HRS is a frequent organ manifestation of acute-on-chronic liver failure; kidney failure is the most common form of organ failure in that setting.

Diagnosis

Diagnostic criteria

HRS-AKI is a diagnosis of exclusion. Diagnostic criteria according to the ICA and ADQI consensus (2024):

• liver cirrhosis with ascites
• acute kidney injury according to KDIGO: rise in serum creatinine of at least 0.3 mg/dL within 48 hours or of at least 50% from baseline within 7 days and/or urine output of at most 0.5 mL/kg per hour for at least 6 hours
• no improvement in creatinine and/or urine output within 24 hours after adequate volume expansion, if clinically required
• no strong evidence of another primary cause of kidney injury, such as septic shock, drug-induced kidney injury, urinary tract obstruction or acute glomerular injury

HRS-AKI may also be present with tubular injury, proteinuria or pre-existing chronic kidney disease. Older criteria, for example those of the 2019 German guideline, instead required serum creatinine above 1.5 mg/dL, no improvement after at least two days of volume expansion with albumin without fluid-removing medicines, and exclusion of shock, nephrotoxic medicines and parenchymal kidney disease (proteinuria above 0.5 g per day, microscopic hematuria with more than 50 red cells per high-power field, abnormal renal ultrasound).

Because many patients with cirrhosis have low muscle mass, creatinine underestimates the loss of renal function; a rapid rise is therefore relevant even below fixed thresholds.

Urine findings and triggers

In addition, a low urinary sodium concentration and a bland urinary sediment support HRS and argue against acute tubular necrosis. Triggers are also sought, in particular spontaneous bacterial peritonitis (diagnostic paracentesis) and gastrointestinal bleeding.

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Further reading (open access)

1. AWMF-Leitlinienregister 021-017: Komplikationen der Leberzirrhose (S2k-Leitlinie DGVS, Fassung 2019)
2. MSD Manual Professional: Systemic Abnormalities in Liver Disease
3. Acute kidney injury in patients with cirrhosis: ADQI and ICA joint multidisciplinary consensus meeting (J Hepatol 2024)
4. Hepatorenal syndrome, a form of acute kidney injury, in patients with cirrhosis: review (Clin Exp Gastroenterol 2021)

Cross-references