From the Guidelines
Cirrhosis with acute kidney injury (AKI) requires prompt management focused on identifying and treating the underlying cause while preserving renal function. The initial approach should include discontinuing nephrotoxic medications (including NSAIDs, ACE inhibitors, ARBs), volume assessment, and albumin administration at 1g/kg (up to 100g) for volume expansion, as recommended by the most recent study 1. Diuretics should be temporarily held. For suspected hepatorenal syndrome (HRS), terlipressin 1-2mg IV every 4-6 hours plus albumin is the preferred treatment, with norepinephrine (0.5-3 mg/hour) as an alternative when terlipressin is unavailable, according to the latest guidelines 1. Midodrine (7.5-12.5mg three times daily) with octreotide (100-200mcg subcutaneously three times daily) can be used in settings without intensive care capabilities. Continuous renal replacement therapy may be necessary for severe cases with metabolic derangements. The pathophysiology involves splanchnic vasodilation leading to effective arterial underfilling, intense renal vasoconstriction, and decreased glomerular filtration rate, as explained in 1. Early recognition and treatment are crucial as mortality is high, particularly with HRS. Liver transplantation evaluation should be expedited as it represents the definitive treatment for eligible patients with cirrhosis and AKI.
Some key points to consider in the management of AKI in cirrhosis include:
- Discontinuing nephrotoxic medications and holding diuretics
- Volume assessment and expansion with albumin
- Use of vasoconstrictors such as terlipressin or norepinephrine for HRS
- Consideration of liver transplantation evaluation
- Monitoring for complications such as pulmonary edema and metabolic derangements
It is essential to note that the management of AKI in cirrhosis should be individualized and based on the underlying cause and severity of the disease, as well as the patient's overall clinical condition, as recommended by 1.
From the FDA Drug Label
The efficacy of TERLIVAZ was assessed in a multicenter, double-blind, randomized, placebo-controlled study (CONFIRM) (NCT02770716). Patients with cirrhosis, ascites, and a diagnosis of HRS-1 with a rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2. 25 mg/dL and meeting a trajectory for SCr to double over two weeks, and without sustained improvement in renal function (<20% decrease in SCr and SCr ≥2. 25 mg/dL) 48 hours after both diuretic withdrawal and the beginning of plasma volume expansion with albumin were eligible to participate. A total of 300 patients were enrolled; the median age was 55 years (range: 23 to 82), 60% were male, and 90% were White. At baseline, 40% had alcoholic hepatitis and 19% had ACLF Grade 3; the mean serum creatinine was 3. 5 mg/dL, and the mean MELD score was 33. The primary efficacy endpoint was the incidence of Verified HRS Reversal, defined as the percentage of patients with 2 consecutive SCr values of ≤1. 5 mg/dL, obtained at least 2 hours apart while on treatment by Day 14 or discharge.
The answer to the question about Cirrhosis and AKI is that terlipressin (IV), also known as TERLIVAZ, has been shown to be effective in reversing Hepatorenal Syndrome (HRS), a type of Acute Kidney Injury (AKI), in patients with cirrhosis. The study found that a greater proportion of patients achieved Verified HRS Reversal in the TERLIVAZ arm compared to the placebo arm 2.
- Key findings:
- 29.1% of patients in the TERLIVAZ arm achieved Verified HRS Reversal, compared to 15.8% in the placebo arm.
- The durability of HRS Reversal was also higher in the TERLIVAZ arm, with 31.7% of patients achieving HRS Reversal without renal replacement therapy to Day 30, compared to 15.8% in the placebo arm.
From the Research
Definition and Diagnosis of Acute Kidney Injury in Cirrhosis
- Acute kidney injury (AKI) is a common complication of advanced cirrhosis, with various definitions and criteria for staging its severity, including the RIFLE, AKIN, and KDIGO groups 3.
- The hepatology community has mostly embraced the AKIN diagnostic and staging criteria, which incorporate changes in serum creatinine and urine output in the definition and staging of AKI 3.
- However, the AKIN criteria have not been strictly applied in all studies on cirrhosis, leading to some confusion in the interpretation of results 3.
Causes and Management of Acute Kidney Injury in Cirrhosis
- The cause of AKI in cirrhosis is multifactorial and can be subdivided into either functional or structural, with functional causes including volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome) 4.
- Management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause, with albumin-based volume resuscitation recommended in prerenal AKI and vasoconstrictor therapy used to treat hepatorenal syndrome type 1 5, 6.
- Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion, while direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated glomerulonephritis (GN) 5.
Predictors of Acute Kidney Injury Resolution and Associated Clinical Outcomes
- Clinical predictors of AKI resolution in hospitalized patients with cirrhosis include higher albumin value at the time of admission and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis, while a higher creatinine value at the time of admission is associated with lower odds of AKI resolution 7.
- AKI resolution during index admission is associated with improved short- and long-term transplant-free survival, with patients with resolved AKI experiencing higher 90-day survival rates and greater transplant-free survival compared to those with unresolved AKI 7.
- The use of terlipressin in patients with acute-on-chronic liver failure (ACLF) and AKI has been shown to be effective in reversing AKI, with approximately 35% of patients responding to treatment and experiencing improved survival 6.