Table 1 Outcomes

Primary

Major adverse kidney events to 30 days (MAKE30)

30 days

MAKE30 is defined as:

1) Death due to any cause censored at 30 days after enrollment OR

2) Provision of RRT, any modality, within 30 days of trial enrollment OR

3) Sustained loss of kidney function (100% increase of serum creatinine from baseline at 30 ± 7 days)

Baseline serum creatinine: eGFR (120 ml/min/1.73m²) will be used to impute an estimated baseline value. This estimate will be applied to all patients as most patients will not have a baseline value from within the 3 months preceding study

30-day serum creatinine: these will only be required for participants with an elevated value at the time of fluid pathway termination who do not receive RRT

Secondary

Significant extrarenal complications of HUS (life-threatening)

30 days

a. Neurologic

i. Seizures requiring anticonvulsant therapy

ii. Coma: depressed mental state requiring mechanical ventilation for airway protection and/or ventilatory support

iii. Thrombotic or hemorrhagic stroke confirmed by neuroimaging

b. Cardiac

i. Myocardial infarction: elevated troponin and electrocardiographic features of myocardial ischemia with cardiologist assignment of myocardial infarction

ii. Myocarditis: elevated troponin along with cardiologist assigned diagnosis of myocarditis

iii. Myocardial dysfunction: reduced ejection fraction requiring inotropic agents

iv. Cardiopulmonary arrest requiring cardiopulmonary resuscitation and/or extracorporeal membrane oxygenation

v. Arrhythmias requiring electrical or chemical cardioversion or pharmacological anti-arrhythmic therapy

c. Respiratory

i. Respiratory failure requiring invasive mechanical ventilation (i.e., via an endotracheal tube)

ii. Pleural effusions requiring thoracostomy or thoracentesis

d. Gastrointestinal

i. Hyperglycemia requiring insulin therapy at time of hospital discharge

ii. Bowel obstruction/perforation requiring surgical repair

iii. Intussusception requiring reduction

iv. Acute cholecystitis requiring decompression

v. Pancreatitis with lipase > 3.0 × upper limit of normal (ULN) for age

vi. Hepatitis/liver failure when any one of the following biochemical criteria are met: bilirubin (when other liver functions are in the normal range) > 3.0 × ULN; bilirubin (when accompanied by any increase in other liver function test) > 1.75 × ULN; AST, ALT, and GGT > 8 × ULN

vii. Ascites requiring paracentesis

a. Infectious complications

i. Bacteremia with or without hypotension requiring inotropic support

ii. Peritonitis with or without hypotension requiring inotropic support

Secondary

Development of HUS of any severity (i.e., including those who do not meet the MAKE30 endpoint among those without HUS at randomization)

30 days

HUS is defined as [19]:

1) Anemia (hematocrit level < 30%) AND

2) Thrombocytopenia (platelet count < 150 × 10³/mm³) AND

3) AKI (serum creatinine concentration > upper limit of reference range for age)