BERLIN—The Acute Kidney Injury Network (AKIN) criteria for acute renal failure (ARF) better predicted survival over a period of 90 days in a study of hospitalized patients with cirrhosis when compared with current criteria, according to a study presented at the  46th Annual Meeting of the European Association for the Study of the Liver.

Renal failure in cirrhosis is currently defined as a serum creatinine level greater than 1.5 mg/dL, but senior author Pere Ginès, MD, Chairman of the liver unit in the Hospital Clinic in Barcelona and Professor of Medicine at the University of Barcelona in Spain, noted two shortcomings of this definition. First, 1.5 mg/dL represents a very low glomerular filtration rate (GFR), and second, it may be insensitive to changes in GFR because it does not take into account changes in serum creatinine levels.

Comparing the AKIN criteria to the current definition, which is more than 20 years old, Dr. Ginès said,

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“The idea was to see if this [new] definition adjusts or could be used in the field of renal failure in patients with liver disease.”

The AKIN criteria for acute renal failure are an absolute increase in serum creatinine of 0.3 mg/dL or greater or a 50% or greater increase over baseline in a 48-hour period. The researchers stratified patients meeting these criteria into two groups: those with a peak serum creatinine level of greater than 1.5 mg/dL and those with peak values less than or equal to 1.5 mg/dL.

In this first prospective observational trial of this patient population to assess the value of the AKIN criteria to predict outcome, the investigators enrolled 300 consecutive patients admitted to the hospital for complications of cirrhosis between July 2009 and December 2011. At baseline, patients had an average age of 60 years, and 60% were men, and 51% had alcoholic cirrhosis. Serum bilirubin was 4.6 mg/dL, International Normalized Ratio 1.6, and serum creatinine 1.3 mg/dL. Patients were followed up for three months.

While hospitalized, 88 patients (29%) experienced renal failure according to the AKIN criteria. At three months, 38% were alive compared with 87% of the 212 patients without renal failure, a significant difference between the groups. The 60 patients meeting AKIN criteria and having a peak serum creatinine greater than 1.5 mg/dL had a significantly lower survival rate compared to the 28 AKIN criteria patients with peak creatinine levels at or below 1.5 mg/dL (29% vs. 58%).

The 30 patients with elevated creatinine levels but not meeting AKIN criteria had a three-month survival rate of 80%. Multivariate analyses indicated that both the AKIN criteria and the current criteria for ACR are independent predictors of survival, but the AKIN criteria provide higher predictive power, the investigators said.

They concluded that the development of renal failure according to the AKIN criteria is common among patients hospitalized with cirrhosis and leads to poor outcomes “even when small increases in serum creatinine are considered,” something the older definition of renal failure does not take into account.

“We combined two definitions, the new definition and the old definition, and we came up with a subclassification of patients, which was associated with outcomes, so we think that this could be  potentially a new way of defining renal failure in cirrhosis,” Dr. Ginès predicted.

“We found that patients without renal failure have an excellent survival, which at three months was above 85%. Patients meeting the AKIN criteria but with a peak value of serum creatinine below 1.5 [mg/dL], which was below the former definition [of ARF], had a survival of around 56%.,” he told Renal & Urology News. “And then patients with the AKIN definition plus a peak value of serum creatinine above 1.5 had a much worse prognosis. So I think that the combination of the old and the new definition is helping us in making a better discrimination with the respect to outcome of patients.”

The study continues to enroll patients, and Dr. Ginès would like to see it replicated in a multi-center setting and involving at least 1,000 patients. If the AKIN criteria are validated for patients with cirrhosis, he foresees a change in practice “because you may treat the disease more aggressively if you know that prognosis is very poor,” including putting the patient on a transplant waiting list.

Mauro Bernardi, MD, Professor of Internal Medicine at the University of Bolgna in Bologna, Italy, commented that the study addresses an important issue. “The problem we have in hepatology is related to the fact that these patients have muscle wasting. They do not produce creatinine,” he said. So serum creatinine “is not an absolutely reliable marker of renal function in this specific context.”

Dr. Bernardi views the concept of the change in serum creatinine level over time as the most important part of the AKIN criteria in the liver disease setting. A higher but stable level in a patient with chronic renal failure may be a lower risk than for a patient with a lower one but who “is doubling his serum creatinine in a very short time because he is experiencing an acute renal failure,” he said.