Table 3 |.
Experimental therapies for S-AKI
| Treatment | Property/mechanism of action | Comment |
|---|---|---|
| Blood purification | ||
| High-volume hemofiltration | Convection enhances removal of large molecule proinflammatory cytokines | No survival benefit, increased the rate of hypophosphatemia and hypokalemia, reduced circulating cytokine level (see text) |
| High cutoff membrane | Large pore membrane (average 20 nm in diameter) allows removal of large molecule cytokines | Compared with conventional CRRT in patients with S-AKI, the use of high cutoff membrane significantly reduced circulating levels of inflammatory cytokines and improved hemodynamics, but no effect on mortality was observed.153–159 Excessive amounts of albumin were also lost. |
| Adsorptive therapy | ||
| Polymyxin B hemoperfusion | Synthetic membrane coated with polymyxin B that binds endotoxin | Improved hemodynamic parameter and monocyte and neutrophil function with controversy on survival benefit (see text) |
| CytoSorb | Porous polymer beads; adsorption of cytokines, myoglobin, free hemoglobin, bilirubin/bile acid | Reduce circulating IL-6, improve hemodynamics, no survival benefit160–162 |
| oXiris | Surface-treated AN69 membrane with PEI and coated with heparin; adsorption of endotoxin and cytokines | Reduced SOFA score at 48 h.163 Ongoing RCTs are investigating the effectiveness of this treatment (ENDoX, ; oXiris, ). |
| HA-330 | Neutral microporous resin; adsorption of cytokines, complements, free hemoglobin | Improved hemodynamics and organ function, shortened ICU stay, and reduced ICU mortality164 |
| LPS adsorbers | Synthetic polypeptide bound to porous polyethylene discs; adsorption of endotoxins | A case series in patients with gram-negative sepsis reported improvement of hemodynamics and decreased endotoxin level but no effect on survival.165–167 |
| CPFA | Combined plasma separation with adsorption and hemodialysis; removes inflammatory mediators | No survival benefit, technical issue (clotted), high cost.168 Additional RCTs are pending (COMPACT 2, ; ROMPA, ). |
| Pharmacologic therapy | ||
| Human recombinant alkaline phosphatase | Dephosphorylation of endotoxins and proinflammatory mediators such as extracellular adenosine triphosphate, which is released by mitochondria in response to inflammation and hypoxia | No significant improvement in short-term kidney function was found compared with placebo use. Mortality at day 28 was found to be reduced with AP.169 |
| Angiotensin II | Potent vasoconstrictor to increase blood pressure (effect on efferent arterioles > afferent arterioles); potent vasopressor, without inotropic or chronotropic properties | Pilot study in patients with catecholamine-resistant shock showed restored blood pressure and increase urine output.170 Subgroup analysis in patients with high-output shock with AKI requiring RRT showed angiotensin II associated with an improved survival and a higher rate of renal recovery.171 Ongoing RCT aims to evaluate the effect of angiotensin II on hemodynamics and urine output in patients with S-AKI (ASK-IT, ). |
| Levocarnitine | Enhance fatty acid entry into the mitochondria; antioxidant, anti-inflammatory, and antiapoptotic actions | Did not improved organ dysfunction in septic shock.172 Ongoing RCT aims to explore the effect of levocarnitine as an adjunctive treatment for patients with S-AKI (CarniSave, ) |
| Reltecimod (AB103) | CD28 antagonist prevents binding of bacterial superantigens to the CD28 T-cell receptor | Ongoing phase 2 RCT of reltecimod versus placebo in patients with S-AKI; aims to assess recovery from AKI and safety (Phase 2 Study of Reltecimod Versus Placebo in Patients With Sepsis-associated Acute Kidney Injury, ). |
AP, alkaline phosphatase; ASK-IT, Angiotensin in Septic Kidney Injury Trial; CarniSave, L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury trial; COMPACT 2, Combining Plasma-Filtration and Adsorption 2 trial; CPFA, coupled plasma filtration adsorption; CRRT, continuous renal replacement therapy; ENDoX, Effects of a Polyethylene-Coated Membrane (oXiris) for Hemofiltration Versus Polymyxin B–Immobilized Fiber Column (Toraymyxin) for Hemoperfusion on Endotoxin Activity and Inflammatory Conditions in Septic Shock study; IL-6, interleukin-6; LPS, lipopolysaccharides; oXiris, Comparing Cytokines, Toxins Adsorbing oXiris Filter to ST150 Filter During CRRT in Patients With Septic Shock trial; PEI, polyethyleneimine; RCT, randomized controlled trial; ROMPA, Mortality Reduction in Septic Shock by Plasma Adsorption trial; RRT, renal replacement therapy; S-AKI, sepsis-associated acute kidney injury; SOFA, Sequential Organ Failure Assessment.