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

Acute Kidney Injury Clinical Trial

— GLOBAL-AKI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05387811
• Other study ID #: AOP2414
• Status: Completed
• Start date: July 1, 2022
• Est. completion date: November 30, 2023

Study information

• Verified date: January 2024
• Source: Azienda Ospedaliera di Padova
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1456
• Est. completion date: November 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Fibrosis
• Hepatorenal Syndrome
• Liver Cirrhosis
• Wounds and Injuries

Intervention

Combination Product:
• Crystalloids, albumin, vasoconstrictors, diuretics, renal replacement therapy
Adherence to International Club of Ascites recommendations for the management of AKI

Locations

Country	Name	City	State
Argentina	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
Brazil	Hospital Federal de Bonsoccesso	Rio De Janeiro
Chile	Universidad de Chile	Santiago
China	Shanghai Jiao Tong University School of Medicine	Shanghai
Denmark	Hvidovre Hospital	Copenaghen
Egypt	Ain Shams University	Cairo
Ethiopia	Black Lion Hospital	Addis Ababa
France	Jean Minjoz University Hospital	Besançon
France	Hospital Beaujon	Clichy
Germany	University of Aachen	Aachen
Germany	University Hospital Munich	Munich
Hungary	Hospital of Debrecen	Debrecen
India	Institute of Liver and Biliary Sciences	New Delhi
Italy	IRCCS Azienda Ospedaliera-Universitaria di Bologna	Bologna
Italy	Università La Sapienza - Latina	Latina
Italy	Hospital Niguarda Milan	Milano
Italy	University and Hospital of Padua	Padua
Italy	Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino	Torino
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang
Korea, Republic of	Hallym University College of Medicine	Chuncheon
Mexico	Central Military Hospital	Mexico City
Mexico	Hospital General	Mexico City
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"	Mexico City
Netherlands	Erasmus Medical Center	Rotterdam
Paraguay	Hospital de Clínicas Facultad de Ciencias Médicas U.N.A.	Asunción
Peru	Hospital Nacional D.A. Carrion	Lima
Poland	Medical University of Warsaw	Warsaw
Russian Federation	University of Moscow	Moscow
Spain	Hospital Clinic	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Baylor University Medical Center	Dallas	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Ochsner Medical Center	New Orleans	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera di Padova

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  China,  Denmark,  Egypt,  Ethiopia,  France,  Germany,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Paraguay,  Peru,  Poland,  Russian Federation,  Spain, 

References & Publications (1)

Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G. Diagnosis and management of acute kidney injury in patients with cirrhosis: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Transfer to intensive care unit	Transfer to intensive care unit	Hospital stay (up to 90 days)
Other	Mechanical ventilation	Patients receiving mechanical ventilation	Hospital stay (up to 90 days)
Other	Renal replacement therapy	Patients receiving renal replacement therapy	Hospital stay (up to 90 days)
Other	Indication to RRT	Patients with indications to receive renal replacement therapy	Hospital stay (up to 90 days)
Primary	90-day Mortality	Mortality at 90 days	90 days
Secondary	Phenotypes of acute kidney injury across geographic areas	Characteristics of acute kidney injury (clinical type and stage)	Hospital stay (up to 90 days)
Secondary	Staging of acute kidney injury across geographic areas	Characteristics of acute kidney injury (clinical type and stage)	Hospital stay (up to 90 days)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	In-hospital mortality	Mortality during hospital stay	Hospital stay (up to 90 days)
Secondary	28-day mortality	Mortality at 28 days	28 days
Secondary	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