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

Completed

• Conditions: Acute Kidney Injury; Hepatorenal Syndrome; Liver Cirrhosis

• Registration Number: NCT05387811
• Lead Sponsor: Azienda Ospedaliera di Padova

Brief Summary

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:

1. To establish the severity of AKI across different regions

2. To identify precipitants of AKI across different centers

3. To identify the phenotypes of AKI across different centers

4. To evaluate differences in the management of AKI across different centers and their impact on clinical outcomes

5. To assess outcomes of acute kidney injury (resolution of AKI, in-hospital mortality, 28-day mortality, 90-day mortality)

Detailed Description

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

Study Timeline

• Study First Submitted: 2022-05-16
• Study First Submitted QC: 2022-05-19
• Study First Posted: 2022-05-24
• Study Start: 2022-07-01
• Primary Completion: 2023-09-30
• Study Completion: 2023-11-30
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-29
• Last Update Posted: 2024-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1456

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

1. Age < 18 years old;
2. Pregnancy;
3. 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);
4. Extrahepatic malignancy other than non-melanoma skin cancer within last 5 years;
5. 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);
6. Previous solid organ transplantation;
7. HIV infection with CD4 ≤ 250/µL;
8. Patients who cannot provide prior informed consent and no legal surrogate decision maker

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
90-day Mortality	90 days	Mortality at 90 days

Secondary Outcome Measures

Name	Time	Method
28-day mortality	28 days	Mortality at 28 days
Progression of AKI	Hospital stay (up to 90 days)	Progression of AKI will be defined as transition of AKI to a higher stage and/or need for RRT.
Staging of acute kidney injury across geographic areas	Hospital stay (up to 90 days)	Characteristics of acute kidney injury (clinical type and stage)
Resolution of AKI	Hospital stay (up to 90 days)	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
Phenotypes of acute kidney injury across geographic areas	Hospital stay (up to 90 days)	Characteristics of acute kidney injury (clinical type and stage)
Adherence to the International Club of Ascites recommendations for the management of AKI	Hospital stay (up to 90 days)	Proportion of patients receiving treatment according to the International Club of Ascites recommmentations for the management of acute kidney injury
In-hospital mortality	Hospital stay (up to 90 days)	Mortality during hospital stay
Development of CKD	90 days	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

Trial Locations

Locations (38)

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Ochsner Medical Center; 🇺🇸 New Orleans, Louisiana, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Hospital de Gastroenterología "Dr. Carlos Bonorino Udaondo"; 🇦🇷 Buenos Aires, Argentina

Hospital Italiano; 🇦🇷 Buenos Aires, Argentina

Hospital Nacional Prof. Alejandro Posadas; 🇦🇷 El Palomar, Argentina

Universidad de Rosario; 🇦🇷 Rosario, Argentina

Hospital Federal de Bonsoccesso; 🇧🇷 Rio De Janeiro, Brazil

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