Clinical trial NCT05387811: International Registry of Acute Kidney Injury in Cirrhosis: The GLOBAL AKI Project
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Cirrhosis
Acute Kidney Injury
Hepatorenal Syndrome
Keywords: AKI
International Club of Ascites
Cirrhosis
Global
Lead sponsor: Azienda Ospedaliera di Padova
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 1456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

Eligibility criteria: 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

Primary outcomes:
measure: 90-day Mortality
timeFrame: 90 days
Secondary outcomes:
measure: Phenotypes of acute kidney injury across geographic areas
timeFrame: Hospital stay (up to 90 days)
measure: Staging of acute kidney injury across geographic areas
timeFrame: Hospital stay (up to 90 days)
measure: Adherence to the International Club of Ascites recommendations for the management of AKI
timeFrame: Hospital stay (up to 90 days)
measure: Progression of AKI
timeFrame: Hospital stay (up to 90 days)
measure: Resolution of AKI
timeFrame: Hospital stay (up to 90 days)
measure: In-hospital mortality
timeFrame: Hospital stay (up to 90 days)
measure: 28-day mortality
timeFrame: 28 days
measure: Development of CKD
timeFrame: 90 days
Other outcomes:
measure: Transfer to intensive care unit
timeFrame: Hospital stay (up to 90 days)
measure: Mechanical ventilation
timeFrame: Hospital stay (up to 90 days)
measure: Renal replacement therapy
timeFrame: Hospital stay (up to 90 days)
measure: Indication to RRT
timeFrame: Hospital stay (up to 90 days)
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital de Gastroenterología "Dr. Carlos Bonorino Udaondo"
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: El Palomar
country: Argentina
facility: Hospital Nacional Prof. Alejandro Posadas
city: Rosario
country: Argentina
facility: Universidad de Rosario
city: Rio De Janeiro
country: Brazil
facility: Hospital Federal de Bonsoccesso
city: Santiago
country: Chile
facility: Universidad de Chile
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine
city: Copenaghen
country: Denmark
facility: Hvidovre Hospital
city: Cairo
country: Egypt
facility: Ain Shams University
city: Addis Ababa
country: Ethiopia
facility: Black Lion Hospital
city: Besançon
country: France
facility: Jean Minjoz University Hospital
city: Clichy
country: France
facility: Hospital Beaujon
city: Aachen
country: Germany
facility: University of Aachen
city: Munich
country: Germany
facility: University Hospital Munich
city: Debrecen
country: Hungary
facility: Hospital of Debrecen
city: New Delhi
country: India
facility: Institute of Liver and Biliary Sciences
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliera-Universitaria di Bologna
city: Latina
country: Italy
facility: Università La Sapienza - Latina
city: Milano
country: Italy
facility: Hospital Niguarda Milan
city: Padua
country: Italy
facility: University and Hospital of Padua
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Chuncheon
country: Korea, Republic of
facility: Hallym University College of Medicine
city: Mexico City
country: Mexico
facility: Central Military Hospital
city: Mexico City
country: Mexico
facility: Hospital General
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Asunción
country: Paraguay
facility: Hospital de Clínicas Facultad de Ciencias Médicas U.N.A.
city: Lima
country: Peru
facility: Hospital Nacional D.A. Carrion
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Moscow
country: Russian Federation
facility: University of Moscow
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
Study officials:
affiliation: Azienda Ospedaliera di Padova
name: Salvatore Piano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.