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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Kidney Injury, Hepatorenal Syndrome

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No AKI<br>Patients with cirrhosis admitted to hospital with bacterial infection with initial serum creatinine below 1.5mg/dL. | |
| AKI and Infection<br>Patients with cirrhosis admitted to hospital with bacterial infection and initial serum creatinine above 1.5mg/dL. | |
| AKI with No Infection<br>Patients with cirrhosis admitted to hospital with initial serum creatinine above 1.5mg/dL without bacterial infection. | |

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGAL, Acute kidney injury, Cirrhosis, Hepatorenal syndrome