The aim of this study is to evaluate:

• The diagnostic performance of Fractional Excretion of Urea (FEUrea) for the differential diagnosis of acute kidney injury in patients with cirrhosis and ascites presenting to a tertiary care hospital.

• The ability of Fractional Excretion of Urea to distinguish between

  1. structural group of acute kidney injury (acute tubular necrosis) versus functional group of acute kidney injury (prerenal azotemia and hepatorenal syndrome), and
  2. types of functional group (prerenal azotemia versus hepatorenal syndrome type 1).

Acute kidney injury (AKI) is a common complication of end-stage liver disease and is one of the criteria that define acute-on-chronic liver failure.

There are two types of AKI in cirrhosis: functional and structural. The functional group is divided into the volume responsive prerenal azotemia (PRA) that results from decreases in intravascular volume (e.g., aggressive diuretic treatment, diarrhea) and volume-unresponsive state or called hepatorenal syndrome (HRS). AKI that is unresponsive to albumin infusion and withdrawal of diuretics in the absence of identifiable causes. The structural group includes acute tubular necrosis (ATN) that results from intrinsic damage and other renal parenchymal disorders.

Urea is filtered in the glomerulus and then largely reabsorbed in the proximal tubule and also in the distal tubule. The reabsorption of urea is increased by vasopressin and the renin-angiotensin-aldosterone system. The fractional excretion of urea under conditions of decreased renal perfusion and increased vasopressin and renin-angiotensin-aldosterone system (RAAS), such as that seen in cirrhosis with PRA or HRS type 1, should therefore decrease. Conversely, renal tubular injury should impair reabsorption and increase its fractional excretion. Since urea absorption is largely modulated in the proximal tubules, it is not affected by diuretics acting more distally. Recently it is therefore hypothesized that the fractional excretion of urea (FEUrea) could serve as a clinical aid in making an early distinction between ATN versus PRA and HRS type 1 in patients with cirrhosis and ascites presenting with AKI. The current study was designed to test this hypothesis.

Inclusion Criteria:

• Age greater than 18 years.
• Decompensated liver cirrhosis (Child-Pugh classification B or more) of any etiology diagnosed by clinical parameters involving laboratory tests, endoscopic or radiologic evidence of cirrhosis, history of decompensation (hepatic encephalopathy, ascites, variceal bleeding, jaundice), and liver biopsy if available.
• Use of either loop diuretics and/or distal diuretics (ex; spironolactone and eplerenone) until the time of admission.
• Availability of a baseline serum creatinine as defined by the International Club Ascites.

Exclusion Criteria:

• Prior liver or kidney transplant
• Advanced chronic kidney disease defined as serum creatinine greater than 4 mg/dL
• Patients on acute or chronic renal replacement therapy
• Patients with hepatocellular carcinoma.

Potential patients will be identified by screening all cirrhotic patients who will be admitted with acute kidney injury to a specialized hepatology inpatient unit or who will attend for follow up at outpatient clinics