hepatorenal syndrome (HRS)

Last edited 03/2023 and last reviewed 04/2023

Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease (1)

Hepatorenal syndrome (HRS) has been defined as a purely ‘‘functional” type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.

• diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent
• in contrast to other causes of acute kidney injury (AKI), hepatorenal syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs
• renal failure is thought to be due to reduced renal blood flow - more marked in the cortex than the medulla - due to cortical vasoconstriction
• basis for the reduced perfusion is uncertain but may result from the accumulation of a vasoactive substance, thought to be endotoxin, which is usually cleared in the liver.
• relative adrenal insufficiency (RAI) is present in 24-47% of patients with decompensated cirrhosis and ascites and may play a role in the development HRS (2)
  

Previously Hepatorenal syndrome was classified into two clinical types:

• type 1
• defined as rapid reduction of renal function by doubling of initial serum creatinine to a concentration of at least 2.5 mg/dL or a 50% reduction in less than two weeks in the initial 24 hour creatinine clearance to below 20 mL/min, or,
• type 2
• which renal failure progression did not meet the criteria for type I

The International Club of Ascites (ICA) updated the definition of hepatorenal syndrome (HRS) type 1 which is now termed HRS-AKI (acute kidney injury).

AKI is a broad clinical syndrome encompassing various aetiologies that cause either direct injury to the kidney (structural injury) or an acute impairment of function (functional injury)

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define AKI as any of the following:

1) increase in sCr by >=0.3mg/dl (>=26.5μmol/L) within 48h; or

2) increase in sCr to >=1.5x baseline, which is known or presumed to have occurred within the prior 7days; or 3) urine volume <0.5ml/kg/h for 6h

New diagnostic criteria for HRS-AKI

*The evaluation of this parameter requires a urinary catheter. **This criterion would not be included in cases of known pre-existing structural chronic kidney disease (e.g. diabetic or hypertensive nephropathy). AKI, acute kidney injury; FENa, fractional excretion of sodium; HRS, hepatorenal syndrome; ICA, International Club of Ascites

If functional kidney injury in patients with cirrhosis that does not meet the criteria for HRS-AKI then this is termed

• HRS-NAKI (that is, non-AKI)
• defined by estimated glomerular filtration rate (eGFR) rather than serum creatinine
• NAKI is sudivided into:
• HRS acute kidney disease (HRS-AKD) if the eGFR is less than 60 mL/min/1.73 m2 for less than three months, or,
• HRS chronic kidney disease (HRS-CKD) if the eGFR is less than 60 mL/min/1.73 m2 for more than three month

The kidneys are morphologically normal and, when transplanted into patients with chronic renal failure, function normally.

The condition is characterised by oliguria, hyponatraemia and uraemia. Urine sodium is low (less than 10 mmol) as renal tubular function is preserved

• note though that urinary sodium can be elevated secondary to diuretics, frequently used in this group of patients with ascites

The condition is often irreversible and rapidly fatal - patients who develop hepatorenal syndrome have a 95% chance of dying from it, and a mean survival of under 2 weeks (4):

• the outcome of patients with hepatorenal syndrome, as well as recovery of kidney function, is strongly dependent upon reversal of the hepatic failure, whether spontaneous, following medical therapy, or following successful liver transplantation

Terlipressin:

• in patients with type 1 hepatorenal syndrome terlipressin may cause serious or fatal respiratory failure at a frequency higher than previously known, and that terlipressin increases the risk of sepsis and septic shock (5)
  • consider the individual benefits and risks for patients with type 1 hepatorenal syndrome when initiating terlipressin treatment, especially for those with severe renal or hepatic impairment and monitor all patients closely during terlipressin treatment

Reference:

• Angeli P, Garcia-Tsao G, Nadim MK, Parikh CR. News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document. J Hepatol 2019;71:811-22. doi:10.1016/j. jhep.2019.07.002.
• EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018; 69: 406–460.
• Simonetto DA et al. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ 2020;370:m2687http://dx.doi.org/10.1136/bmj.m2687
• Drug and Therapeutics Bulletin (2003), 41 (7), 49-52.
• Terlipressin: new recommendations to reduce risks of respiratory failure and septic shock in patients with type 1 hepatorenal syndrome Drug Safety Update volume 16, issue 8: March 2023: 2.