Highlights
- The LIBERATE-D trial compared a conservative (indication-driven) dialysis strategy to a conventional (thrice-weekly) strategy in patients with dialysis-requiring acute kidney injury (AKI-D).
- Conservative dialysis was associated with a higher unadjusted rate of kidney function recovery at hospital discharge (64% vs 50%, P = .04).
- Patients in the conservative group received significantly fewer dialysis sessions (median 1.8 vs 3.1 sessions per week) and experienced fewer episodes of dialysis-associated hypotension.
- While the primary outcome lost statistical significance after prespecified adjustments (P = .15), the findings suggest that ‘less may be more’ when facilitating renal recovery.
The Burden of Dialysis-Requiring Acute Kidney Injury
Acute kidney injury requiring kidney replacement therapy (AKI-D) represents one of the most severe complications in hospitalized patients, particularly those in intensive care units. Beyond the immediate metabolic and fluid challenges, the transition from acute injury to chronic kidney disease (CKD) or end-stage renal disease (ESRD) remains a major concern. Persistent dependence on dialysis is linked to increased morbidity, higher mortality rates, and a profound reduction in quality of life. Furthermore, the economic burden on healthcare systems is substantial, as AKI-D survivors often require prolonged hospitalizations and specialized outpatient care.
Historically, once a patient starts dialysis for AKI, the default approach has been to continue treatment on a regular schedule—typically three times per week—until significant improvements in urine output or laboratory parameters are observed. However, emerging evidence suggests that the dialysis process itself, particularly through episodes of intradialytic hypotension, may cause ‘recurrent hits’ to the recovering tubules, effectively stunning the kidney and delaying spontaneous recovery. The LIBERATE-D (Liberation From Acute Dialysis) trial was designed to challenge this conventional paradigm by testing whether a more restrained approach could facilitate faster renal liberation.
Study Design and Methodology
The LIBERATE-D trial was a multicenter, unblinded, randomized superiority trial conducted across four clinical sites in the United States between 2020 and 2025. The study enrolled 221 participants who met specific criteria: they had AKI-D, a baseline estimated glomerular filtration rate (eGFR) greater than 15 mL/min/1.73 m2, and were hemodynamically stable enough for planned intermittent hemodialysis.
The Interventions
Participants were randomized into two distinct treatment arms:
- Conservative Strategy: In this group, dialysis was not performed on a set schedule. Instead, clinicians initiated dialysis only when specific metabolic or clinical indications were met, such as refractory hyperkalemia, severe metabolic acidosis, or symptomatic fluid overload.
- Conventional Strategy: This group followed the standard of care, receiving intermittent hemodialysis three times per week. Treatment continued until the patient met prespecified urine output or creatinine clearance thresholds for weaning.
The primary endpoint was unadjusted kidney function recovery at hospital discharge, defined as being alive and dialysis-independent for at least 14 consecutive days. Secondary endpoints included the number of dialysis sessions per week, dialysis-free days up to day 28, and the incidence of adverse events such as hypotension.
Key Findings: A Shift Toward Less Intervention
The results of the LIBERATE-D trial provide compelling data on the potential benefits of reducing dialysis intensity during the recovery phase of AKI.
Primary Outcome: Kidney Function Recovery
In the unadjusted analysis, the conservative strategy appeared significantly superior. Seventy of the 109 participants (64%) in the conservative group achieved kidney function recovery at discharge, compared to 55 of 109 (50%) in the conventional group. This represented a 13.8% absolute difference (95% CI, 0.8%-26.8%; P = .04). However, when the researchers applied prespecified adjustments for baseline characteristics, the odds ratio shifted to 1.56 (95% CI, 0.86-2.84; P = .15), crossing the threshold for statistical significance but still favoring the conservative approach.
Secondary Outcomes and Treatment Burden
The secondary outcomes strongly favored the conservative arm. Patients managed with the indication-only approach received a median of 1.8 dialysis sessions per week, compared to 3.1 sessions in the conventional arm—a reduction of nearly 1.4 sessions per week. Additionally, the conservative group enjoyed significantly more dialysis-free days by day 28 (median 21 days vs 5 days; difference of 16 days), suggesting a much faster transition to independence.
Safety and Hemodynamic Stability
Safety data revealed that dialysis-associated hypotension occurred less frequently in the conservative group (69 events) than in the conventional group (97 events). This is a critical finding, as intradialytic hypotension is a known risk factor for delayed kidney recovery due to transient ischemic injury to the already vulnerable renal parenchyma.
Expert Commentary and Clinical Interpretation
The LIBERATE-D trial touches on a fundamental tension in nephrology: the balance between ‘cleaning the blood’ and ‘allowing the kidney to rest.’ While the conventional strategy ensures tight control of solutes and fluid, the LIBERATE-D data suggests that this rigor might come at the cost of renal auto-recovery.
The loss of statistical significance in the adjusted analysis of the primary endpoint suggests that while the signal for benefit is strong, the study may have been underpowered to account for the heterogeneity of AKI patients. Nevertheless, the clinical implications are noteworthy. By reducing the number of dialysis sessions, the conservative strategy not only lowers the risk of hypotension but also reduces the logistical and physical burden on patients, reduces the risk of catheter-related infections, and potentially lowers healthcare costs.
Mechanistically, the ‘kidney stunning’ hypothesis remains the most plausible explanation for these results. Each dialysis session involves rapid fluid shifts and potential inflammatory triggers. In a patient whose kidneys are attempting to repair their tubular architecture, these repeated hemodynamic stresses may be counterproductive. The LIBERATE-D trial provides the first high-quality randomized evidence that waiting for clinical indications rather than following a calendar may be the better path forward for stable patients.
Conclusion and Future Directions
The LIBERATE-D trial demonstrates that a conservative dialysis strategy in stable AKI-D patients results in fewer dialysis sessions and potentially higher rates of kidney recovery. While the adjusted primary analysis suggests some uncertainty regarding the exact effect size, the consistency of the secondary outcomes—including faster recovery times and fewer hypotensive episodes—provides a strong rationale for adopting a more individualized, symptom-driven approach to dialysis in the subacute phase of AKI.
Clinical practice may need to shift away from ‘reflexive’ thrice-weekly dialysis in patients who show signs of stabilization. However, as the authors conclude, these findings should ideally be validated in a larger, more diverse patient population to confirm the impact on long-term renal outcomes and survival.
Funding and Clinical Registry
The study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Trial registration: ClinicalTrials.gov Identifier: NCT04218370.
References
Liu KD, Siew ED, Tuot DS, et al. A Conservative Dialysis Strategy and Kidney Function Recovery in Dialysis-Requiring Acute Kidney Injury: The Liberation From Acute Dialysis (LIBERATE-D) Randomized Clinical Trial. JAMA. 2026;335(4):326-335. doi:10.1001/jama.2025.21530.
