Study objectives:

To determine whether, in critically ill patients with Acute Kidney Injury requiring renal replacement therapy (AKI-RRT), randomization to receive intravenous hyperoncotic albumin 20-25% (100 mL X two doses) compared to control/placebo normal saline boluses (100 mL X two doses) given during RRT sessions, leads to:

1. An increase in organ support-free days (primary outcome) at 28 days following randomization; and
2. An increase in RRT-free days (principal secondary outcome) at 28 days following randomization.

Background: Severe Acute Kidney Injury that necessitates renal replacement therapy (AKI-RRT) is a frequent complication of critical illness and portends severe outcomes: high morbidity, an approximately 50% risk of in-hospital death, and increased healthcare resource utilization. Although life-saving when needed, RRT itself may contribute to the poor outcomes associated with AKI-RRT. Since RRT treatments frequently cause hypotension, repeated episodes of kidney and other organ ischemia may occur during RRT. Hypotension during RRT is often triggered by fluid removal. At the same time, there is some evidence that more aggressive ultrafiltration could be beneficial in AKI-RRT.

Albumin is a protein that is the primary contributor to the colloid oncotic pressure maintaining the effective circulating volume (ECV) during RRT. Critically ill patients with AKI-RRT are nearly always hypoalbuminemic. Despite its high cost and limited evidence to support the practice, intravenous hyperoncotic albumin is commonly administered to patients with AKI-RRT in an effort to boost the colloid oncotic pressure and maintain the blood pressure while simultaneously facilitating fluid removal

Objective:

This proposed trial is intended to provide definitive evidence as to the efficacy of a frequently used and expensive intervention to promote hemodynamic stability and augment ultrafiltration during RRT in critically ill patients

Design: A randomized controlled trial with two parallel arms. Setting: The mixed medical-surgical intensive care units of five Canadian tertiary care hospitals with plans to expand to include other centres across Canada and internationally.

Study Population: 856 patients admitted to the Intensive Care Unit (ICU) with AKI requiring treatment with RRT .

Intervention: Participants will be randomized 1:1 to receive either albumin (20-25%) boluses or normal saline placebo boluses at the start and halfway through RRT sessions in ICU, during their RRT treatments to a maximum of 14 days.

Inclusion Criteria:

• Age ≥18 years old;
• Admission to a critical care unit/intensive care unit (ICU) for > 24 hours;
• Receiving vasoactive therapy AND/OR undergoing mechanical ventilation (including non-invasive mechanical ventilation (NIMV));
• Immediate initiation of RRT for management of AKI is planned OR additional RRT sessions are imminently planned for patients who already received RRT during their ICU admission;

Exclusion Criteria:

• Initiation of RRT for reasons other than AKI (e.g. drug intoxication, hypothermia) ;

• Known pre-hospitalization end-stage kidney disease;

• Kidney transplant within the past 365 days;

• Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis;

• Advanced cirrhosis (Child Pugh class C [score 10-15]), spontaneous bacterial peritonitis or hepatorenal syndrome;

• Acute peritoneal dialysis used as the initial RRT modality;

• Contraindications to albumin:

  1. Admitted with traumatic brain injury
  2. Increased intra-cranial pressure in those with intra-cranial pressure monitoring
  3. Prior history of anaphylaxis to intravenous albumin
  4. Contraindication or known objection to albumin/blood product transfusions

• Already received 2 or more RRT sessions during ICU admission.

• Limitations of medical therapy precluding RRT/mechanical ventilation/vasoactive medications or plan to transition to palliation

De-identified individual participant data collected during the ALTER-AKI trial will be shared with researchers who provide a detailed and methodologically sound proposal, with specific aims. Data sharing will be for the purposes of medical research, with specific data elements provided to answer the research questions in the proposal, and under the auspices of the consent under which the data were originally gathered

Data availability will commence 6 months after the publication of the primary and secondary analyses, with no anticipated end date

Qualified researchers will need to sign a data sharing and access agreement and will need to confirm that data will only be used for the agreed upon purpose for which data access was granted. The decision to grant access will be made by the trial co-principal investigators, with involvement of the trial steering committee as needed. Proposals to access ALTER-AKI data should be directed to the trial principal investigator via email: Edward Clark--edclark@toh.ca. Costs of preparing and providing partial datasets will be charged to requesting investigators

Blood Banks at participating sites prepare intravenous hyperoncotic albumin and normal saline (control) in identical infusion mini-bags. Opaque bags and intravenous tubing covers will be used to maintain blinding as much as possible.

The packaging for normal saline and 25% albumin will be identical (mini-bags) and be covered. The intravenous tubing will have an opaque sleeve to mask any colour discrepancy in the 2 product