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Diagnostic criteria

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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

Diagnostic criteria
• Cirrhosis; acute liver failure; acute-on-chronic liver failure

• Increase in serum creatinine >=0.3 mg/dl within 48 h or >=50% from baseline value according
to ICA consensus document

and/or

Urinary output <=0.5 ml/kg B.W. >=6 h*

• No full or partial response, according to the ICA consensus document20, after at least 2 days of diuretic withdrawal and volume expansion with albumin. The recommended dose of albumin is 1 g/kg of body weight per day to a maximum of 100 g/day

• Absence of shock

• No current or recent treatment with nephrotoxic drugs

• Absence of parenchymal disease as indicated by proteinuria >500 mg/day, microhaematuria

(>50 red blood cells per high power field), urinary injury biomarkers (if available) and/or abnormal renal ultrasonography**.

Suggestion of renal vasoconstriction with FENa of <0.2% (with levels <0.1% being highly
predictive)

*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

New classification of hepatorenal syndrome (1):

HRS-1 is now HRS-AKI

HRS1 > HRS-AKI

a) Absolute increase in sCr >=0.3 mg/dl within 48 h
and/or
b) Urinary output <= 0.5 ml/kg B.W. >=6 h*
or
c) Percent increase in sCr >=50% using the last available value of outpatient sCr within 3 months as the baseline value

HRS-2 is now HRS-NAKI (which has subclassifications HRS-AKD and HRS-CKD)

HRS-AKD	a) eGFR <60 ml/min per 1.73 m2 for <3 months in the absence of other (structural) causes b) Percent increase in sCr <50% using the last available value of outpatient sCr within 3 months as the baseline value
HRS-CKD	a) eGFR <60 ml/min per 1.73 m2 for >=3 months in the absence of other (structural) causes

AKD, acute kidney disease; AKI, acute kidney injury; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HRS, hepatorenal syndrome; sCr, serum
creatinine.
* the evaluation of this parameter requires a urinary catheter.

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.

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