Study of Accuracy of NGAL, a Renal Injury Biomarker, in Patients With Cirrhosis

Urinary Biomarker NGAL in Decompensated Cirrhosis: Early Prediction of AKI and of Treatment Response

The purpose of this study is to test the accuracy of urinary neutrophil-gelatinase associated lipocalin (NGAL) and other biomarkers (plasma renin, norepinephrine) to predict acute kidney injury (AKI) development in patients with cirrhosis and bacterial infection and to predict response to AKI treatment with albumin and albumin with terlipressin in patients with suspected hepatorenal syndrome.

Study Overview

• Status: Unknown
• Conditions: Acute Kidney Injury; Hepatorenal Syndrome

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Rafael O Ximenes, MD; Phone Number: +55 011 2661-3338; Email: rximenes@gmail.com

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-010
    • Recruiting
    • University of Sao Paulo
    • Contact: Rafael O Ximenes, MD; Phone Number: +55011 2661-3338; Email: rximenes@gmail.com
    • Principal Investigator: Alberto Q Farias, Assoc. Prof.
    • Principal Investigator: Ana LC Martinelli, Assoc. Prof.
    • Principal Investigator: Flair J Carrilho, Professor
  • Espirito Santo
    • Vitoria, Espirito Santo, Brazil, 29075-910
      • Not yet recruiting
      • Federal University of Espirito Santo
      • Contact: Luciana L Goncalves, Ph. D.; Email: lucianalofego@terra.com.br
      • Principal Investigator: Luciana L Goncalves, Ph. D.
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Recruiting
      • Federal University of Rio Grande do Sul
      • Contact: Mario RA Silva, Assoc. Prof.; Email: marioreis@live.com
      • Principal Investigator: Mario RA Silva, Assoc. Prof.
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083-887
      • Not yet recruiting
      • University of Campinas
      • Contact: Daniel FC Mazo, PhD
      • Contact: Email: danielmazo@yahoo.com.br
      • Principal Investigator: Daniel FC Mazo, PhD

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: Non-Probability Sample

Study Population

We will include cirrhotic patients admitted to hospitals participating centers with AKI and/or bacterial infection.

Description

Inclusion Criteria:

• Cirrhosis diagnosis by liver biopsy or combination of clinical, laboratorial, endoscopic and imagenological data;
• Presence of ascites and/or hepatic hydrothorax;
• Age over 18 years old;
• Diagnosis of bacterial infection (including spontaneous bacterial peritonitis and others) with or without acute kidney injury (defined as a serum creatinine above 1.5mg/dL at admission) or acute kidney injury without bacterial infection;
• Agreement to participate in the study, registered by informed consent;

Exclusion Criteria:

• Serious comorbidities (functional class IV heart failure, O2 dependent chronic obstructive pulmonary disease, advanced cancer);
• Shock, as defined by American College of Chest Physicians;
• Chronic kidney disease with serum creatinine persistently above 1.5mg/dL in the previous 6 months and/or with sonographic findings of chronic nephropathy;
• Intrinsic nephropathy with hematuria over 50 red cells/high power field and dysmorphic erythrocyte and/or proteinuria over 500mg/24h;
• Use of nephrotoxic drugs in the previous 30 days;
• Dialysis prior to study inclusion;
• Previous solid organ transplantation.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
No AKI; Patients with cirrhosis admitted to hospital with bacterial infection with initial serum creatinine below 1.5mg/dL.
AKI and Infection; Patients with cirrhosis admitted to hospital with bacterial infection and initial serum creatinine above 1.5mg/dL.
AKI with No Infection; Patients with cirrhosis admitted to hospital with initial serum creatinine above 1.5mg/dL without bacterial infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of NGAL to predict no response to albumin expansion	We will build a receiver-operating curve and calculate the area under the curve to determine the accuracy of NGAL to predict no response to albumin expansion. No response will be defined as an absence of a drop of serum creatinine to a final value below 1.5mg/dL in the day after the end of albumin expansion. Albumin will be administrated as International Ascites Club recommendations, i.e. in the dose of 1g/kg/day for 2 days in patients with suspected hepatorenal syndrome.	One day after albumin expansion (day 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of urinary NGAL and other biomarkers to predict no response to hepatorenal syndrome treatment	We will test the accuracy of urinary NGAL and other biomarkers to predict no response to hepatorenal syndrome treatment. No response to treatment will be defined as a final value of serum creatinine above 1.5mg/dL after the end of treatment with terlipressin plus albumin. The treatment will be conducted according to International Ascites Club recommendations.	Treatment period (maximum of 14 days)
Accuracy of urinary NGAL and other biomarkers to predict development and progression of acute kidney injury (AKI) in patients with bacterial infection	We will test the accuracy of urinary NGAL and other biomarkers to predict AKI development and progression during antibiotic therapy and during hospital stay in patients with bacterial infection. AKI will be defined by ICA-AKI criteria.	During antibiotic therapy and during hospital stay
Predictors of mortality	We will test clinical and laboratorial data relationship with in-hospital, 30 days and 90 days mortality in a univariate analysis. Associated variables will be tested in a multivariate analysis.	In-hospital, 30 days and 90 days
Urinary NGAL as a predictor of adverse events of AKI treatment in cirrhosis	We will build a receiver-operating curve and calculate the area under the curve to determine the accuracy of urinary NGAL to predict adverse events during AKI treatment with albumin alone or in combination with terlipressin. We will also calculate the best cut-off value based on the receiver-operating curve.	During treatment period
Accuracy of other biomarkers to predict no response to albumin expansion	We will test the accuracy of other biomarkers to predict no response to albumin expansion. No response will be defined as an absence of a drop of serum creatinine to a final value below 1.5mg/dL in the day after the end of albumin expansion. Albumin will be administrated as International Ascites Club recommendations, i.e. in the dose of 1g/kg/day for 2 days in patients with suspected hepatorenal syndrome.	One day after albumin expansion (day 3)

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Federal University of Rio Grande do Sul; University of Campinas, Brazil; Hospital de Base; Federal University of Espirito Santo
• Investigators: Study Chair: Alberto Q Farias, Associate professor, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 27, 2014
• First Posted (Estimate): January 29, 2014

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Cirrhosis; Acute kidney injury; NGAL; Hepatorenal syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Fibrosis; Acute Kidney Injury; Hepatorenal Syndrome
• Other Study ID Numbers: NGAL01