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

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

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)

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Acute Kidney Injury; Hepatorenal Syndrome
• Intervention / Treatment: Combination product: Crystalloids, albumin, vasoconstrictors, diuretics, renal replacement therapy

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 Type: Observational
• Enrollment (Actual): 1456

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Italiano
  • Buenos Aires, Argentina
    • Hospital de Gastroenterología "Dr. Carlos Bonorino Udaondo"
  • El Palomar, Argentina
    • Hospital Nacional Prof. Alejandro Posadas
  • Rosario, Argentina
    • Universidad de Rosario
• Brazil
  • Rio De Janeiro, Brazil
    • Hospital Federal de Bonsoccesso
• Chile
  • Santiago, Chile
    • Universidad de Chile
• China
  • Shanghai, China
    • Shanghai Jiao Tong University School of Medicine
• Denmark
  • Copenaghen, Denmark
    • Hvidovre Hospital
• Egypt
  • Cairo, Egypt
    • Ain Shams University
• Ethiopia
  • Addis Ababa, Ethiopia
    • Black Lion Hospital
• France
  • Besançon, France
    • Jean Minjoz University Hospital
  • Clichy, France
    • Hospital Beaujon
• Germany
  • Aachen, Germany
    • University of Aachen
  • Munich, Germany
    • University Hospital Munich
• Hungary
  • Debrecen, Hungary
    • Hospital of Debrecen
• India
  • New Delhi, India
    • Institute of Liver and Biliary Sciences
• Italy
  • Bologna, Italy
    • IRCCS Azienda Ospedaliera-Universitaria di Bologna
  • Latina, Italy
    • Università La Sapienza - Latina
  • Milano, Italy
    • Hospital Niguarda Milan
  • Padua, Italy, 35128
    • University and Hospital of Padua
  • Torino, Italy
    • Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino
• Korea, Republic of
  • Anyang, Korea, Republic of
    • Hallym University Sacred Heart Hospital
  • Chuncheon, Korea, Republic of
    • Hallym University College of Medicine
• Mexico
  • Mexico City, Mexico
    • Hospital General
  • Mexico City, Mexico
    • Central Military Hospital
  • Mexico City, Mexico
    • Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• Paraguay
  • Asunción, Paraguay
    • Hospital de Clínicas Facultad de Ciencias Médicas U.N.A.
• Peru
  • Lima, Peru
    • Hospital Nacional D.A. Carrion
• Poland
  • Warsaw, Poland
    • Medical University of Warsaw
• Russian Federation
  • Moscow, Russian Federation
    • University of Moscow
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clinic
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with cirrhosis admitted to hospital for the treatment of a complication of liver disease (ascites, gastrointestinal bleeding, hepatic encephalopathy, bacterial infections, jaundice, etc)

Patients without AKI will enter in a screening period during the hospitalization to identify patients with hospital-acquired AKI.

For patients that will not develop AKI during hospitalization, no other visits will be performed during the study, except for the discharge and follow-up visits.

Description

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 Plan

How is the study designed?

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfer to intensive care unit	Transfer to intensive care unit	Hospital stay (up to 90 days)
Mechanical ventilation	Patients receiving mechanical ventilation	Hospital stay (up to 90 days)
Renal replacement therapy	Patients receiving renal replacement therapy	Hospital stay (up to 90 days)
Indication to RRT	Patients with indications to receive renal replacement therapy	Hospital stay (up to 90 days)

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Padova
• Investigators: Principal Investigator: Salvatore Piano, MD, Azienda Ospedaliera di Padova

Publications and helpful links

General Publications

• 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: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015 Apr;62(4):968-74. doi: 10.1016/j.jhep.2014.12.029. Epub 2015 Jan 28. No abstract available. Erratum In: J Hepatol. 2015 Jul;63(1):290.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cirrhosis; AKI; Global; International Club of Ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fibrosis; Wounds and Injuries; Liver Cirrhosis; Acute Kidney Injury; Hepatorenal Syndrome; Physiological Effects of Drugs; Natriuretic Agents; Diuretics; Vasoconstrictor Agents
• Other Study ID Numbers: AOP2414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No