International Registry of Acute Kidney Injury in Cirrhosis: The GLOBAL AKI Project

Study Overview
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Brief Summary
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The aims of this study will be to identify the clinical characteristics, the management and the outcomes of acute kidney injury in patients with cirrhosis worldwide. Specific aims: To establish the severity of AKI across different regions To identify precipitants of AKI across different centers To identify the phenotypes of AKI across different centers To evaluate differences in the management of AKI across different centers and their impact on clinical outcomes To assess outcomes of acute kidney injury (resolution of AKI, in-hospital mortality, 28-day mortality, 90-day mortality)

Detailed Description
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Each center will then include patients with cirrhosis who are admitted to the hospital with AKI upon admission or who develop AKI during the hospital stay, and who provide signed informed consent. Acute kidney injury will be defined according to the International Club of Ascites Acute Kidney Injury criteria The following precipitating events of AKI will be considered: volume loss/excessive diuretic use, spontaneous bacterial peritonitis (SBP), non-SBP infection, gastrointestinal bleeding, nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs, contrast media), other causes and no identifiable precipitant. AKI will be classified in the following phenotypes: Hypovolemia-induced AKI: history of excessive fluid losses (i.e., excessive diuresis due to diuretic therapy with loss of body weight >500 g/day or 1,000 g/day in patients without and with edema, respectively; severe diarrhea) or bleeding the days before AKI and improving with fluid administration. HRS-AKI: all the following should be present: a) ascites; b) lack of regression of AKI to a lower stage or resolution of AKI after 2 days of diuretic withdrawal and volume expansion with albumin (1 g/kg of body weight per day to a maximum of 100 g/day); c) absence of shock; d) no current or recent treatment with nephrotoxic drugs; d) absence of parenchymal disease as indicated by proteinuria >500 mg/day, microhaematuria (>50 red blood cells per high power field), urinary injury biomarkers (if available) and/or abnormal renal ultrasonography. Patients will be followed from admission until liver transplantation, death or 90 days, whichever occurs first. Data collected will include demographic, clinical and biochemical information, such as AKI severity, phenotype and evolution. There will be particular emphasis on collecting data regarding the initial management of AKI occurring in the first 2 to 3 days. Furthermore, basic demographic and disease information will be collected in hospitalized patients with cirrhosis who do not develop AKI during the stay to determine the true burden of AKI in this patient population. Data will be registered on an electronic case report form (eCRF) using the Research Electronic Data Capture Software REDCap. ATN-AKI: presence of at least three out of six of the following criteria: a) FeNa > 2%; b) urinary osmolality <400 mOsm/L; c) urinary sodium > 40 mEq/L; d) presence of shock or use of nephrotoxic drugs; e) urine sediment showing granular/epithelial casts; f) urine sediment showing renal tubular epithelial cells. Other parenchymal nephropathy: patients with signs of parenchymal nephropathy not qualified for a diagnosis of ATN-AKI (e.g. IgA nephropathy, glomerulonephritis, nephrotic syndrome, etc.) Post renal AKI: AKI caused by urinary tract obstruction (kidney/bladder stones, prostatic hyperplasia) and resolved after removal of obstruction Unclassified/other AKI: Other types of AKI not fulfilling the afore mentioned phenotypes

Official Title
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Characteristics and Management of Acute Kidney Injury in Hospitalized Patients With Cirrhosis: a Multicenter Intercontinental Observational Prospective Study: The International Club of Ascites GLOBAL AKI Project

Conditions
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Liver Cirrhosis, Acute Kidney Injury, Hepatorenal Syndrome

Intervention / Treatment
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* Combination Product: Crystalloids, albumin, vasoconstrictors, diuretics, renal replacement therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a) Patients with cirrhosis admitted to hospital for the treatment of a complication of liver disease (ascites, gastrointestinal bleeding, hepatic encephalopathy, bacterial infections, jaundice, etc) Exclusion Criteria: Age < 18 years old; Pregnancy; Hepatocellular carcinoma outside Milan criteria (i.e., a single lesion <5 cm or multiple lesions [maximum of three], the largest of which measures ≤ 3 cm); Extrahepatic malignancy other than non-melanoma skin cancer within last 5 years; Previously known severe extrahepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe congestive heart disease [NYHA class ≥ 3]; severe chronic obstructive pulmonary disease [GOLD class ≥ 3], psychiatric disorders); Previous solid organ transplantation; HIV infection with CD4 ≤ 250/µL; Patients who cannot provide prior informed consent and no legal surrogate decision maker

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

| Intervention/Treatment |
| --- |
|Combination Product: Crystalloids, albumin, vasoconstrictors, diuretics, renal replacement therapy|Adherence to International Club of Ascites recommendations for the management of AKI|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day Mortality | Mortality at 90 days | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotypes of acute kidney injury across geographic areas | Characteristics of acute kidney injury (clinical type and stage) | Hospital stay (up to 90 days) | 
| Staging of acute kidney injury across geographic areas | Characteristics of acute kidney injury (clinical type and stage) | Hospital stay (up to 90 days) | 
| Adherence to the International Club of Ascites recommendations for the management of AKI | Proportion of patients receiving treatment according to the International Club of Ascites recommmentations for the management of acute kidney injury | Hospital stay (up to 90 days) | 
| Progression of AKI | Progression of AKI will be defined as transition of AKI to a higher stage and/or need for RRT. | Hospital stay (up to 90 days) | 
| Resolution of AKI | Resolution of AKI will be defined as return of serum creatinine to a value within 0.3 mg/dl (26.5 mmol/L) of the baseline value. Partial response will be defined as regression of AKI to a lower stage with a reduction of serum creatinine to ≥0.3 mg/dl (26.5 mmol/L) above the baseline value | Hospital stay (up to 90 days) | 
| In-hospital mortality | Mortality during hospital stay | Hospital stay (up to 90 days) | 
| 28-day mortality | Mortality at 28 days | 28 days | 
| Development of CKD | Chronic kidney disease will be defined as an estimated glomerular filtration rate <60 ml/min ml/min/1.73 m2 for >3 months. The Modification of Diet in Renal Disease equation will be used for estimating glomerular filtration rate | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AKI, International Club of Ascites, Cirrhosis, Global