Fractional Excretion of Urea for the Differential Diagnosis of Acute Kidney Injury in Cirrhosis

Diagnostic Performance of Fractional Excretion of Urea in Acute Kidney Injury in Patients With Liver Cirrhosis

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Eman A Sabet, Professor; Phone Number: 00200102907077; Email: eman_thabet@med.sohag.edu.eg
• Study Contact Backup: Name: Mahmoud Kh Mahmoud, Doctor; Phone Number: +201092292409; Email: mahmoud.khalaf@med.aswu.edu.eg

Study Locations

• Egypt
  • Aswan, Egypt
    • Recruiting
    • Aswan university hospitals
    • Contact: mahmoud.khalaf@med.aswu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; Acute kidney injury due to acute tubular necrosis
Group 2; Acute kidney injury due to prerenal azotemia
Group 3; Acute kidney injury due to hepatorenal syndrome type 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fractional excretion of urea percentage in urine	By equation : [(urine Na ÷ serum Na) ÷ (urine creatinine ÷ serum creatinine)] x 100%	"through study completion, an average of 1 year".

Collaborators and Investigators

• Sponsor: Sohag University
• Investigators: Principal Investigator: Eman A Sabet, Professor, Suhag University

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: cirrhosis; hepatorenal syndrome; ascites; acute tubular necrosis; pre-renal azotemia
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Fibrosis; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: Soh-Med-21-07-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No