Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - A Randomized Clinical Trial in Acute Kidney Injury (NEUTRALIZE-AKI)

Inclusion Criteria: Admitted to an ICU requiring CKRT: Must have AKI stage 2 or greater at the time of CKRT initiation. Must have been on CKRT for at least 12 hours but no greater than 48 hours at the time of enrollment. At least 18 years of age but not older than 80 at the time of enrollment. One additional life-threatening organ dysfunction present. Acceptable vascular access for CKRT to include adequate lumen size (at least 11.5 Fr for IJ, 13.5 Fr for femoral), and length of catheters (15cm for IJ, 24cm for femoral sites). Initial (non-binding) commitment to maintaining current level of care for at least 96 hours. C-Reactive Protein >3.5 mg/dl. Exclusion Criteria: Not expected to survive next 24 hours. Anticipated transition to comfort measures or hospice in next 4 days. Terminal condition whereby the patient is not expected to survive 28 days or any condition in which therapy is regarded as futile by the PI. Malignancy which is actively being treated or may be treated by chemotherapy or radiation. Hospitalization >14 days during this hospital admission and/or prior transfer from an outside hospital at the time of screening. Active COVID-19 infection with a primary admission diagnosis of COVID-19. Acute or chronic use of ventricular assist devices. ESRD requiring chronic kidney replacement therapy. History of CKD (greater than Stage 3). AKI stage 0 or stage 1 at the time of CKRT initiation. Non-ATN AKI diagnosis. We intend on relying on local nephrology subspecialty expertise to reasonably exclude non-ATN diagnoses based on clinical suspicions combined with prespecified objective criteria. If there is a reasonable suspicion that the subject has non-ATN AKI based on this, they will be excluded from the trial. Acute coronary syndromes, acute stroke, or acute major vascular compromise requiring medical or surgical interventions within 48 hours of randomization. Active hemorrhage requiring blood transfusions at the time of screening. Acute on Chronic Liver Failure. Suspicion of hepato-renal syndrome. Presence of any solid organ transplant at any time prior to admission. Severe burns >45% total body surface area. Bone marrow transplant within the last year. Chronic immunosuppression. Individuals who have a history of primary or secondary immune disorders including, but not limited to, HIV or AIDS. Dry weight of >150kg. Platelet count <15,000/mm3. Patient is a prisoner or member of a vulnerable population. Patient is pregnant or breast feeding. Concurrent enrollment in another interventional clinical trial. Use of any other investigational drug or device within the previous 30 days. Requiring plasmapheresis for any reason during the hospitalization.