A Randomized, Controlled Trial to Evaluate Efficacy and Safety of a Highly Selective Semipermeable Membrane (AN-69 Oxiris) in Comparison With a Semi Selective Semipermeable Membrane (Standard AN-69) in COVID-19 Associated Acute Kidney Injury: oXAKI-COV Study.

On March 11th, 2020 the World Health Organization declared the new coronavirus disease (COVID-19) as a global pandemic. In México, approximately 35% of COVID-19 positive patients require hospital admission and 4.4% do it in the intensive care unit. Acute kidney injury (AKI) in mild to moderate COVID-19 disease seems to be infrequent; in contrast, critically ill patients or those with a severe disease develop AKI in up to 30% of the cases and nearly half of them will need renal replacement therapy in the form of continuous renal replacement therapy (CRRT). AKI in this context seems to be a marker of multiorgan dysfunction and it produces increased mortality in this population.

Multiple mechanisms of AKI in COVID-19 disease have been proposed: direct injury into podocytes and proximal convoluted tubule cells, organ-organ interactions (lung-kidney axis), and cytokine storm. Of them, the severe cytokine-induced injury seems to be the strongest mechanism participating in AKI in this group of severely ill patients with CRRT need thus representing a valuable therapeutic option.

Lately, extracorporeal blood purification therapies have been proposed as a therapeutic tool for cytokine removal in patients with sepsis (prototype of cytokine storm model). Therefore, new membranes with hemoadsorption capacity have been developed and are now commercially available. The first group of membranes used for patients with sepsis and inflammatory systemic response syndrome was high cut-off semipermeable membranes (HCO) followed by non-selective adsorbent membranes, semi selective semipermeable membranes (AN69), and last highly selective semipermeable (especially those with endotoxin and cytokine adsorption, such as AN69-Oxiris). Although these membranes were designed to improve inflammation, they can also be used as a regular filter in CRTT in patients with AKI. These products can be purchased in our country and internationally but there is scant evidence supporting its efficacy to improve clinical outcomes in patients with overt sepsis.

Highly selective semipermeable membranes (AN69-Oxiris) possess a great capacity for endotoxin adsorption and cytokine removal (interleukin 6 [IL-6], tumor necrosis factor-alfa [TNF-α], C reactive protein [CRP] , and interleukin 1b), representing a valuable therapeutic option in septic shock; these findings have been tested mainly in experimental models. There are human-based studies with non-representative statistical samples in which these membranes appear to improve severity scores without any impact in mortality. This membrane has been used in some regions around the world during the COVID-19 pandemic; recently, Ma et al published two severe COVID-19 patients who were treated with AN69-Oxiris resulting in decreased levels of inflammatory markers (ie, CRP and IL-6) and better lymphocyte counts. However, there is uncertainty in the clinical benefit of those changes.

Given the lack of specific drugs or vaccine targeted for COVID-19 and, taking into account the pathophysiologic basis that supports the use of extracorporeal blood purification therapies to reduce the cytokine storm in COVID-19 infected patients with AKI requiring CRRT, the use of these membranes could be of clinical utility in the disease. Here our group presents a randomized,open-label, controlled trial to evaluate efficacy and safety of a highly selective semipermeable membrane (AN69-Oxiris) in comparison with a semi selective semipermeable membrane ( standard AN69) in COVID-19 associated acute kidney injury.