Septic patients with acute kidney injury (SA-AKI) requiring continuous renal replacement therapies (CRRT) present high mortality due to systemic inflammatory response, cytokine liberation, and finally multiorgan dysfunction. Cytokine plasmatic elimination with continuous venovenous hemofiltration (CVVH) presents frequent complications, known as "dialytrauma", and a high resource cost both technical and human. The study primary end-point is to demonstrate a longer filter life with the use of continuous venovenous hemodialysis (CVVHD) respect to CVVH, both modalities employing the same adsorption capacity membrane. As secondary end-points investigators will try to demonstrate less dialytrauma events of CVVHD respect to CVVH. In order to achieve these objectives investigators have designed a proof of concept exploratory trial that will include those patients whom present SA-AKI meeting CRRT initiation criteria. During the first 72 hours investigators will measure plasmatic elimination capacity of main cytokines, and other clinical and prognostic relevant molecules. Investigators will also measure hemodynamic, respiratory, and metabolic parameters. Adverse effects related to CRRT ("dialytrauma") will also be registrated. Finally, investigators will analyze 90 days survival. Demonstration of a minor complication rate (longer filter patency with less dialytrauma events) with a similar immunomodulating capacity and with its consequent lower cost, should settle the based evidence principles that recommend the use of CVVHD asociated to an adsorption capacity membrane in patients with SA-AKI whom need CRRT.

Investigators will warrant a correct protocol application. Study data will be reviewed by an external monitoring committee from the clinical assay research central unit (UCICEC - IDIBELL). Monitors will contrast registered data from the collection data form (CDF) with data from patient´s medical record. All patient´s medical records will be indefinitely saved in electronical format to be reviewed if necessary.

Patients who meet inclusion criteria will be randomized for one of both arms with aleatory assignation using a randomisation sequential (RndSeq) program for Statistical Package for the Social Sciences (SPSS). Adverse events will be reported (in less than 24 hours if severe) to the sponsor center to be properly evaluated. If the severe adverse event (SAE) is finally evaluated by the study board as related to the intervention arm, urgent notification to health authorities must proceed and study should be interrupted until further decision.

As a pilot study of at least 50 cases is advisable in many circumstances (Sim and Lewis, 2012), and we wanted to compare two treatment options, we aimed to recruit at least 100 patients.

Missing data will try to be avoided by an exhaustive patient´s follow up by study investigators. Intention to treat analysis (ITT) will be the main strategy and statistical substitution techniques for missing data will be applied when necessary. Per protocol analysis will also be done to avoid possible bias. Out-of-range results will be identified and processed with adequate statistical techniques.

Data registry has been created to include all variables with written individual data collection forms (DCF). Data will be bedside registered by the study members but final software database registration will be done by the statistics outside investigator who has no contact with patients situation. Cytokines levels will be introduced in DCF when measured (every six months).

Statistical analysis will be done by the statistics investigator who wont have any role in patient´s selection, randomization, or follow up. SPSS v. 18.0 for statistical analysis will be used. Variable distribution will be studied and logarithmic transformation will be used on those variables that don't present normal distribution, presumably cytokine levels. Univariate analysis comparing clinical, demographic, biochemical, metabolic, hemodynamic and respiratory baseline variables between both arms (CVVHD-ST150 and CVVH-ST150), will be done with two-tailed t test for continuous variables and chi-square test for categorical variables. Variables determined several times (T0, T24, T48, T72) will be analysed using a one-way repeated measures ANOVA test in order to demonstrate differences between both arms. Multivariate analysis will be completed to control those clinically relevant confounding variables as well as to discover baseline differences. According to hypothesis and to the dependent variable on study investigators will use a survival analysis (to study mortality) with a cox regression model, or a hierarchic multiple linear regression model when the dependent variable is continuous (for example dialytrauma score). Arm intervention (CVVHD, CVVH) will be considered as the main independent variable adding other control independent variables.

As the study is measuring cytokine levels in five different moments (T0, T24, T48, T72), in order to maximize statistical power and reduce control variables number, the area under the curve (AUC) we´ll be determined for every cytokine and LPS during the first 72 hours. Due to this statistical maneuver investigators will obtain a continuous variable that represents each cytokine level during the biochemical study period (72 hours). To evaluate if the arm intervention improvement in terms of efficacy and safety could be related to cytokine levels during the first 72 hours, a mediation complementary analysis will be done considering cytokine (represented by AUC) as a mediator between the independent variable (intervention arm) and the effect we study.

Data dictionary. ICU: Intensive Care Unit; AKI: Acute Kidney Injury; CRRT: Continuous Renal Replacement Therapies; IL-1β: interleukin 1β; TNF-α: tumor necrosis factor α; IL-6: interleukin 6, IL-10: interleukin 10; IL-4: interleukin 4; CVVH: Continuous Venovenous Hemofiltration; CVVHD: Continuous Venovenous Hemodialysis; SPSS: Statistical Package for the Social Sciences.

Inclusion Criteria:

• Less than 72 hours from ICU admission to inclusion
• Clinical diagnosis of Severe Sepsis or Septic shock (SCCM definitions)
• Correct therapeutic initial management of septic process (SSC guidelines)
• Clinical diagnosis of Acute Kidney Injury (ADQI definitions)
• Acute Kidney Injury meeting CRRT initiation criteria (ADQI guidelines)
• Written informed consent from patient or legal surrogates

Exclusion Criteria:

• End Stage Renal Disease(ESRD)
• Received previous CRRT or hemodialysis in the last three months
• Inclusion in other ongoing study
• Coexisting illness with a high probability of death
• Immunosuppression