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Patients with cirrhosis are susceptible to acute kidney injury (AKI), which leads to a significant increase in mortality and a risk of progression to chronic kidney disease. Hepatorenal syndrome (HRS) as a specific form of AKI (HRS-AKI) is particularly susceptible to high mortality in patients with advanced cirrhosis and ascites. Early recognition of HRS-AKI is critical, and vasoconstrictors may reverse AKI and serve as a bridge to liver transplantation.
In 2023, the International Ascites Club (ICA) and the Acute Dialysis Quality Organization (ADQI) jointly convened a meeting to develop new diagnostic criteria for HRS-AKI, which provide grading recommendations for the examination, management, and post-discharge follow-up of patients with cirrhosis and AKI.
➢ How to harmonize the definitions of acute kidney injury (AKI), chronic kidney disease (CKD), acute kidney disease (AKD), and renal function recovery in patients with cirrhosis?
1. We recommend using the KDIGO criteria to define AKI in patients with cirrhosis: an increase in serum creatinine (SCr) of ≥0.3 mg/dl (26.5 micromol/L) over 48 hours, or a ≥50% increase from baseline values in the past 7 days, or a urine output (UO) of ≤ 0.5 ml/kg for ≥ 6 hours. (Highly recommended, grade A)
2. We recommend that in patients with cirrhosis, AKD and CKD be defined using the KDIGO criteria. (Highly recommended, grade A)
3. We suggest that in patients with cirrhosis, complete recovery from AKI is defined as SCr recovery to within 0.3 mg/dl (26.5 μmol/L) above baseline levels. (Highly recommended, grade B)
➢ Which serum creatinine (SCr) reference value should be used to define AKI in patients with cirrhosis?
1. We recommend diagnosing and grading AKI using the lowest, stable SCr value obtained within the last 3 months. If no value is available in the last 3 months, the most recent value can be used, up to 12 months ago. (Highly recommended, D grade)
2. In the absence of a known baseline SCr, we recommend taking as a reference the lower of the following values: SCr at admission or SCr calculated from an estimated glomerular filtration rate (eGFR) of 75 ml/min/1.73 m². (Weak Recommendation, Grade B)
➢ What are the diagnostic criteria for AKI DUE TO HRS (HRS-AKI)?
1. HRS-AKI is a phenotype of AKI specific to patients with advanced cirrhosis and ascites that may be accompanied by tubular damage, proteinuria, and/or pre-existing CKD. (Unrated).
2. We recommend the following diagnostic criteria for HRS-AKI:
a) cirrhosis with ascites;
b) 48小时内SCr增加≥0.3 mg/dl(26.5 μmol/L)或7天内SCr较基线值增加≥ 50%，或UO ≤ 0.5 ml/kg 持续 ≥ 6 小时；
c) no improvement in SCr and/or UO within 24 hours of adequate volume resuscitation;
d) There is no strong evidence that other causes are the main causes of AKI. (Unrated)
3. We do not recommend 48 hours of systemic albumin administration as necessary for the diagnosis of HRS-AKI. (Highly recommended, grade D)
4. We propose to replace the historical terms HRS-AKI, HRS-AKD, and HRS-CKD with HRS types 1 and 2 according to the timing and duration of renal insufficiency. (Highly recommended, grade D)
➢ What is the epidemiology and prognosis of renal insufficiency in patients with cirrhosis?
1. AKI and AKD are common in patients with cirrhosis; Prognosis depends on the severity of kidney and liver disease. (Unrated)
2. There is a high risk of developing CKD after AKI, which leads to a worse clinical prognosis. (Unrated)
➢ What are the ways to prevent AKI in patients with cirrhosis?
1. We recommend strategies to mitigate the risk of AKI, including an individualised Renal and Liver Health (KLH) assessment to understand susceptibility to AKI, nephrotoxin management and hepatologist advice for anticipated and accidental exposures. (Best Practice Statement)
2. We recommend the use of 20%-25% albumin for AKI prophylaxis after hepatic venous pressure gradient (LVP) measurements and in patients with SBP. (Highly recommended, grade B). The dose and duration of albumin administration should take into account the patient's hemodynamic and volume status. (Best Practice Statement)
We do not recommend the systematic use of albumin to prevent AKI in non-SBP-infected patients, as well as the use of albumin solely to maintain serum albumin concentrations > 3.0 g/dl, especially in patients with decompensated cirrhosis. (Highly recommended, grade A)
➢ What diagnostic items should be included in the examination of patients with cirrhosis and AKI?
1. We recommend that the diagnostic work-up for AKI in patients with cirrhosis should include similar tools for patients without cirrhosis. (Best Practice Statement)
2. We recommend the use of the Chronic Kidney Disease Epidemiology Cooperative Group (CKD-EPI) eGFR, regardless of ethnic variables, and preferential use of cystatin C to assess renal function, although it may not perform well in patients with low GFR and ascites. (Weak Recommendation, Grade B)
3. In addition to serum creatinine, we suggest adjunctive use of functional and injury-related markers to aid in the timely detection of AKI, characterize different AKI phenotypes, and guide treatment strategies. (Weak Recommendation, Grade B)
➢ What is the strategy for the management of AKI in patients with cirrhosis?
1. We recommend the development of individualized management strategies for the patient's renal and liver health status and AKI phenotype. (Best Practice Statement)
2. We recommend a combination of physical examination, imaging studies, and static and dynamic measurements during fluid management, with frequent reassessment at all stages of treatment to avoid volume overload. (Best Practice Statement)
3. We suggest crystalloid fluid, preferably equilibrium fluid, as first-line treatment for patients with AKI who require fluid resuscitation, unless there is a specific indication for other fluid use. (Highly recommended, grade B)
4. We recommend that in patients with AKI who exhibit signs or symptoms of volume overload, discontinue all fluids and initiate diuretic therapy or RRT. (Best Practice Statement)
5. There is currently insufficient evidence to support routine measurement of intra-abdominal pressure in patients with tension ascites and AKI. (Unrated)
6. We recommend that RRT treatment be individualized, taking into account the clinical context and possible life-threatening AKI-related complications. (Best Practice Statement)
7. We recommend a rapid evaluation of liver transplantation (LT) in patients with decompensated cirrhosis after an attack of AKI. (Best Practice Statement)
8. There is insufficient evidence to recommend transjugular intrahepatic portosystemic shunt (TIPS) or extracorporeal liver supportive treatment for AKI. (Unrated)
➢ What are the specific strategies for the management of HRS-AKI?
1. We recommend initiating vasoconstrictor therapy (terlipressin as first-line agent) in combination with 20% to 25% albumin as soon as HRS-AKI is confirmed. (Highly recommended, grade A)
2. We recommend close monitoring of volume status during HRS-AKI treatment. The albumin dose should be adjusted daily according to the patient's volume status, and albumin should be discontinued immediately if there is evidence of volume overload. (Best Practice Statement)
3. If the SCr is not reduced by more than 25%, we recommend increasing the terlipressin dose every 24 hours (highly recommended, grade D); If mean arterial pressure does not increase by ≥10 mmHg from baseline, we suggest increasing the dose of norepinephrine every 4 hours. (Highly recommended, grade B)
4. We recommend discontinuing vasoconstrictor therapy with HRS-AKI in the following cases:
(a) SCr 降低到不超过基线的0.3 mg/dl；
(b) Serious adverse reactions;
(c) no improvement in renal function after 48 hours of use at the maximum tolerated dose;
(d) RRT is required;
(e) Treatment up to a maximum of 14 days. (Highly recommended, grade B)
5. We recommend LT as the definitive treatment for HRS-AKI in selected patients, regardless of response to vasoconstrictive drug therapy. (Highly recommended, grade A)
➢ What are the key elements of post-AKI/AKD care in patients with cirrhosis after they are discharged from the hospital?
1. We recommend individualized post-discharge management of AKI/AKD based on the severity of the patient's kidney and liver disease, with close collaboration between hepatologists and nephrologists. (Best Practice Statement)
2. We recommend that palliative care assessment be considered in an individualized manner, with goals including reducing the burden of disease and discussing goals of care. (Best Practice Statement)
bibliography
Nadim M K, Kellum J A, Forni L, et al. Acute kidney injury in patients with Cirrhosis: Acute disease quality Initiative (ADQI) and international Club of ascites (ICA) joint multidisciplinary consensus meeting[J]. J Hepatol, 2024.
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