Abstract Background and Aims Sepsis is life-threatening organ dysfunction caused by dysregulated body response to an infection. Mortality rate ranging over 60% for septic shock. AKI is final common pathway of this immune dysregulation leading to systemic inflammation (SI) due to uncontrolled circulating levels of pro-inflammatory mediators and cytokine induced direct organ damage. Kidney replacement therapy (KRT) is often required in Sepsis Associated AKI (SA-AKI) and could improve SI removing pathogens and inflammatory factors. Various blood purification techniques have been used: HCO/MCO membranes, hemoperfusion, plasma filtration/adsorption and, anecdotal, Hemo Filtrate Reinfusion Supra (HFR-S): endogenous reinfusion HDF based on adsorbing resin cartridge that remove cytokines and pro-inflammatory mediators, whose full spectrum is not yet know, and myoglobin also. Aim of this study is to test HFR on outcome of SA-AKI in critically ill pts. Method In a retrospective observational study, we evaluated development of AKI requiring KRT in 12 consecutive SA-AKI patients (pts) admitted in the ICU of our two hospitals from December 2022. ESKD pts in chronic dialysis are excluded. SA-AKI were treated with daily IRRT: HFR-S. Given the laboratory operating standards they were daily assessed: urea, creatinine, C-reactive protein (CRP), procalcitonin (PCT), WBC, platelets (PLT), myoglobin, albumin. Mean arterial pressure (MAP), need for vasopressor, and outcome are also evaluated. The values have been reported as mean ± SD or median and interquartile range (IQR). AKI was defined according to KDIGO. Statistical analyzes were performed with the Wilcoxon Signed Rank Test Results Among the 12 pts 9 had AKI III stage. The mean age was 74 ± 8.2 years, 7 were male. 90% were hypertensive, some with heart disease, 50% with CKD (70% G3-KDIGO, 30% G2) 30% were obese or with diabetes, 40% with COPD. All received mechanical ventilation and several antibiotics, 80% received amines. They underwent IRRT by HFR-S with an average of 7 ± 4.9 treatments (range 2-17 sessions); Qb = 235 ± 19.6 ml/m, TT 225.7 ± 28.5 m. UF 407 ± 120 ml/h. HFR-S confirm an expected reduction for urea and creatinin, significant abatement of CRP, PCT and Myoglobin. Albumin remain stable. Neutral is the effect on WBC and PLT whose progress reflects the trend of sepsis. Cardiovascular instability decreased significantly with the treatments allowing the suspension of vasoactive amines as shown by the significant increase in MAP at the end of treatment (Tab. 1) None of those undergoing HFR had poor intradialytic compliance. Four patients did not survive (three had surgical, one pulmonary, complications), 6 patients had renal recovery, 2 patients had chronic dialysis. Conclusion Our experience with HFR may promote a new strategy to decrease SI and support renal recovery in SA-AKI pts even in the not survived. The adsorbing resin is able to efficacy remove proinflammatory cytokines and many other unknow mediators, that lead to improved MAPs and lower critical illness scores, and allow to eliminate myoglobin too. Indeed there is no study on the use of HFR in SA-AKI and very few experience on his use to hypermyoglobinemia. Finally HFR-Supra is safe and is the cheapest technique for SA-AKI in comparison to the other techniques available (e.g. CRRT, HCO, Cytosorb) by excellent cost-effectiveness-sustainability ratio regarding treatment times and staff-sparing. Larger studies could confirm our evidence but, in the meantime, our cases could help to build a new scientific evidence.