What is the treatment for acute kidney injury in patients with cirrhosis, as per the Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting?

From the Guidelines

El tratamiento de la lesión renal aguda (AKI) en pacientes con cirrosis requiere un enfoque sistemático basado en la causa subyacente, y se recomienda iniciar con la administración de albúmina a 1 g/kg (hasta 100g) durante 48 horas, después de retirar diuréticos y tratar factores precipitantes como infecciones bacterianas. La guía de práctica clínica de la Asociación Americana para el Estudio del Hígado (AASLD) 1 sugiere que, en pacientes con cirrosis y AKI, se debe realizar un desafío de volumen con albúmina intravenosa a una dosis de 1 g de albúmina/kg de peso corporal, con un máximo de 100 g/día, durante 48 horas.

• En pacientes con síndrome hepatorrenal (HRS), se recomienda el uso de vasoconstrictores como terlipressina (0,5-2,0 mg i.v. cada 6 horas o infusión continua de 2 g/24 h i.v.) combinados con albúmina 1.
• La terapia de reemplazo renal (RRT) puede ser necesaria para AKI grave, especialmente como puente para el trasplante de hígado, que sigue siendo el tratamiento definitivo para pacientes con cirrosis y disfunción renal persistente 1.
• Es importante destacar que la guía de práctica clínica de la European Association for the Study of the Liver (EASL) 1 también recomienda el uso de vasoconstrictores y albúmina en pacientes con AKI-HRS de grado >1A, y sugiere que la terlipressina más albúmina debe ser considerada como la primera opción terapéutica para el tratamiento de HRS-AKI.
• En resumen, el tratamiento de la lesión renal aguda en pacientes con cirrosis debe ser individualizado y basado en la causa subyacente, y se debe considerar la administración de albúmina, vasoconstrictores y terapia de reemplazo renal según sea necesario, con el objetivo de mejorar la morbimortalidad y la calidad de vida de estos pacientes.

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 greater proportion of patients achieved Verified HRS Reversal in the TERLIVAZ arm compared to the placebo arm (Table 2).

Table 2: Efficacy Analyses TERLIVAZ N = 199 Placebo N = 101 P value CI = confidence interval

• Primary endpoint † Patients with a SCr value of not more than 1. 5 mg/dL while on treatment, by Day 14, or discharge. ‡ Patients with HRS Reversal without renal replacement therapy to Day 30. Verified HRS Reversal*, n (%) 58 (29.1) 16 (15.8) 0.012 95% CI (0.2,0.4) (0.1,0.2)

The treatment of Acute Kidney Injury in patients with cirrhosis using terlipressin (IV), as studied in the CONFIRM trial 2, shows that a greater proportion of patients achieved Verified HRS Reversal in the TERLIVAZ arm compared to the placebo arm.

• The primary endpoint, Verified HRS Reversal, was achieved by 29.1% of patients in the TERLIVAZ arm and 15.8% in the placebo arm.
• Key findings include:
  • Verified HRS Reversal: 58 patients (29.1%) in the TERLIVAZ arm and 16 patients (15.8%) in the placebo arm.
  • Durability of HRS Reversal: 63 patients (31.7%) in the TERLIVAZ arm and 16 patients (15.8%) in the placebo arm. The use of terlipressin (IV) may be beneficial in the treatment of Acute Kidney Injury in patients with cirrhosis, as evidenced by the results of the CONFIRM trial 2.

From the Research

Acute Kidney Injury in Patients with Cirrhosis

• Acute kidney injury (AKI) is a common complication in patients with decompensated cirrhosis, associated with unfavorable outcomes 3.
• The most common causes of AKI in cirrhosis are prerenal azotemia, acute tubular necrosis, and hepatorenal syndrome (HRS) 4.
• HRS is a functional type of prerenal AKI exclusive to cirrhosis that does not respond to volume repletion, and can occur spontaneously or be precipitated by events that worsen vasodilatation 4.

Treatment of Acute Kidney Injury in Cirrhosis

• Management of AKI in cirrhosis should be tailored to the specific underlying etiology 3.
• Albumin-based volume resuscitation is recommended in prerenal AKI, while acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and potentially corticosteroids 3.
• Terlipressin and albumin have been shown to improve renal function in patients with cirrhosis and type I HRS, with a trend to prolong survival 5, 6.
• Vasoconstrictor therapy, such as terlipressin, is the primary treatment for HRS type 1, with the goal of improving renal function and reducing mortality 3, 7.

Hepatorenal Syndrome

• HRS is a form of AKI occurring in patients with advanced cirrhosis, associated with significant morbidity and mortality 7.
• The pathophysiology of HRS involves increasing portal pressures, release of vasodilatory substances, and compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system 7.
• Terlipressin, a synthetic vasopressin analogue, has been shown to be effective in reversing HRS, but its use is not approved in the United States due to concerns about respiratory adverse events and lack of evidence for mortality benefit 7.