An observational study in Acute Kidney Injury, Fluid Overload and Fluid Overload in Dialysis Patients, sponsored by Hospital Las Higueras. Recruiting at 10 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Hospital Las Higueras · Observational
Acute kidney injury (AKI) is common in critically ill patients and is frequently associated with fluid overload, which can worsen clinical outcomes. Continuous renal replacement therapy (CRRT) allows fluid removal through net ultrafiltration (UFNET), but some patients develop hemodynamic instability or signs of poor tissue perfusion during this process.
The purpose of this prospective observational study is to evaluate tolerance to net ultrafiltration in critically ill patients with AKI receiving CRRT. The study will assess clinical, hemodynamic, ultrasound, perfusion, and biochemical parameters before and during fluid removal to identify factors associated with ultrafiltration intolerance.
The investigators hypothesize that alterations in hemodynamic, perfusion, and congestion-related parameters can identify patients at increased risk of ultrafiltration intolerance before the development of overt hypotension. The results may help improve individualized fluid removal strategies and optimize the safety of CRRT in critically ill patients.
Fluid overload is a frequent and clinically relevant complication in critically ill patients with acute kidney injury (AKI). In this setting, continuous renal replacement therapy (CRRT) is frequently used not only for solute control but also as a strategy for controlled fluid removal through net ultrafiltration (UFNET). Although UFNET is central to de-resuscitation, the individual tolerance to fluid removal is highly variable and is not fully captured by blood pressure monitoring alone.
The concept of ultrafiltration intolerance remains poorly standardized. In clinical practice, intolerance is often recognized only after overt hemodynamic instability occurs, such as hypotension, escalation of vasoactive support, or interruption of fluid removal. However, reductions in cardiac output, impaired tissue perfusion, or worsening venous congestion may precede overt hypotension. Therefore, a multiparametric assessment may allow earlier identification of patients at risk.
This is a prospective, observational, analytical study in critically ill adult patients with AKI receiving CRRT with prescribed UFNET. The study does not assign or modify therapeutic interventions. CRRT modality, anticoagulation strategy, UFNET prescription, vasopressor management, fluid administration, and all other clinical decisions will remain under the responsibility of the treating clinical team according to routine care.
The study will characterize the physiological response to UFNET using a structured multiparametric monitoring approach. Recorded domains will include conventional macrohemodynamic variables, vasoactive support, selected advanced hemodynamic variables when available, focused cardiac ultrasound, venous congestion assessment, peripheral perfusion parameters, fluid balance variables, and selected biochemical markers. Functional hemodynamic maneuvers may be performed when feasible and clinically safe.
Data will be collected prospectively using a standardized case report form. Variables will be recorded at predefined time points before and during the early phase of UFNET, with additional off-schedule recordings if clinical signs compatible with intolerance occur. Source data will be obtained from the electronic or paper medical record, bedside monitoring systems, CRRT prescription and treatment records, laboratory results, and ultrasound assessments performed as part of clinical evaluation.
A data dictionary will define each variable, including its source, units, coding, and expected physiological range when applicable. Data quality procedures will include review of completeness, range checks, consistency checks between related variables, and verification of clinically implausible values against source records. The research team will periodically review entered data to identify missing, inconsistent, or out-of-range values.
Data will be anonymized before analysis. No directly identifiable patient information will be stored in the final analytical database. Access to the study database will be restricted to authorized study investigators. Data will be stored using password-protected institutional or investigator-controlled systems according to local confidentiality and ethical requirements.
The planned sample size is 128 participants, including an estimated analytical sample of 116 participants and an approximate 10% over-recruitment to account for incomplete data, missing assessments, or inability to definitively adjudicate the outcome. The sample size was based on an analytical case-control approach aimed at identifying factors associated with ultrafiltration intolerance.
Missing data will be evaluated before statistical analysis. Variables with substantial missingness may be excluded from inferential analyses. For variables with acceptable levels of missingness, available-case analysis will be performed. The extent and pattern of missing data will be reported.
Statistical analysis will include descriptive statistics, comparison between patients who develop ultrafiltration intolerance and those who do not, and exploratory modeling to identify factors independently associated with intolerance. Continuous variables will be summarized using median and interquartile range or mean and standard deviation, as appropriate. Categorical variables will be summarized as frequencies and percentages. Group comparisons will be performed using appropriate parametric or non-parametric tests according to data distribution. Multivariable logistic regression may be used to explore independent predictors, with covariate selection based on clinical relevance and number of events.
The overall objective of this study is to improve the characterization of ultrafiltration intolerance during CRRT and to generate evidence that may support individualized, physiology-guided fluid removal strategies in critically ill patients with AKI.
Adult critically ill patients admitted to participating intensive care units with acute kidney injury requiring continuous renal replacement therapy and prescribed net ultrafiltration as part of routine clinical care.
Exclusion Criteria:
Adult critically ill patients with acute kidney injury receiving continuous renal replacement therapy with prescribed net ultrafiltration. Participants will be prospectively evaluated using a multiparametric monitoring strategy including clinical, hemodynamic, ultrasound, perfusion, and biochemical assessments. Patients will subsequently be classified according to the development or absence of ultrafiltration intolerance during the observation period.
Development of Ultrafiltration Intolerance
Proportion of patients who develop ultrafiltration intolerance according to the protocol-defined composite criteria, including hypotension, increased vasopressor requirements, worsening peripheral perfusion, tissue hypoperfusion, or reduction/interruption of ultrafiltration due to instability.
Time frame: From UFNET initiation (T0) to 24 hours after initiation of net ultrafiltration
Incidence of Ultrafiltration Intolerance
Percentage of participants who develop ultrafiltration intolerance during the observation period.
Time frame: From UFNET initiation (T0) to 24 hours.
Net Ultrafiltration Rate (mL/kg/h)
Prescribed and achieved net ultrafiltration rate during continuous renal replacement therapy.
Time frame: From UFNET initiation (T0) to 24 hours.
Time to First Ultrafiltration Intolerance Event (hours)
Time from UFNET initiation to the first occurrence of ultrafiltration intolerance.
Time frame: From UFNET initiation to 24 hours.
Severity Category of Ultrafiltration Intolerance
Proportion of participants classified as having mild, moderate, or severe ultrafiltration intolerance according to protocol-defined criteria. Higher categories indicate greater severity of intolerance.
Time frame: From UFNET initiation to 24 hours.
Agreement Between Hypotension-Based and Hypoperfusion-Based Definitions of Ultrafiltration Intolerance
Agreement between intolerance defined by hypotension criteria and intolerance defined by tissue hypoperfusion criteria, assessed using Cohen's kappa coefficient.
Time frame: From UFNET initiation to 24 hours.
Cumulative Fluid Balance (mL)
Cumulative fluid balance achieved during the first 24 hours following UFNET initiation.
Time frame: 24 hours after UFNET initiation
Achieved Net Ultrafiltration Volume (mL)
Total net ultrafiltration volume achieved during the observation period.
Time frame: 24 hours after UFNET initiation
Proportion of Participants Achieving Renal Recovery
Percentage of participants who recover kidney function sufficiently to discontinue kidney replacement therapy according to the treating clinical team.
Time frame: Up to 90 days after UFNET initiation
Ventilator-Free Days
Number of days alive and free from invasive mechanical ventilation.
Time frame: Up to 28 days after UFNET initiation
Intensive Care Unit Mortality
Percentage of participants who die during intensive care unit admission.
Time frame: From UFNET initiation up to 90 days or ICU discharge, whichever occurs first
Hospital Mortality
Percentage of participants who die during hospital admission.
Time frame: From UFNET initiation until hospital discharge, assessed up to 180 days
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided — The investigators have not yet determined whether individual participant data (IPD) will be shared. Any future decision regarding data sharing will be made in accordance with institutional policies, ethical approvals, participant confidentiality requirements, and applicable regulations.
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Hospital Las Higueras