Conservative dialysis strategy promotes faster kidney function recovery in severe AKI

In hospitalized patients with acute kidney injury (AKI) requiring dialysis (AKI-D), a conservative strategy appears to lead to more frequent and faster kidney function recovery with fewer dialysis sessions compared with a conventional strategy, as shown in the LIBERATE-D trial.

The primary endpoint of kidney function recovery at hospital discharge was achieved in 64 percent of patients who received dialysis only when specific metabolic or clinical indications were met (conservative strategy) and in 50 percent of those who received dialysis three times per week (conventional strategy) (unadjusted odds ratio, 1.76, 95 percent confidence interval [CI], 1.02–3.03; p=0.04). [JAMA 2025;doi:10.1001/jama.2025.21530]

Furthermore, patients in the conservative strategy group had an earlier recovery, with more consecutive dialysis-free days by day 28 (21 vs 5 days; p<0.001), and received fewer dialysis sessions (median, 1.8 vs 3.1; p<0.001).

Dialysis-associated hypotension occurred less frequently in the conservative vs the conventional strategy group (69 vs 97 events), although the mean ultrafiltration rate per haemodialysis or pure ultrafiltration session was higher (6.4 vs 4.9 mL/kg/h).

Rethinking dialysis targets

“The results suggest the amount of dialysis targeted for delivery to patients with AKI-D should be more nuanced than indicated by current guidelines,” the authors noted.

They argued that there should be different Kt/V targets for different subsets of patients with AKI-D, especially those in early stages of recovery of kidney function.

The current practice of putting patients with AKI-D on dialysis three times a week with a Kt/V of 1.3 is based on data involving patients with AKI-D who were much more acutely ill than LIBERATE-D study participants and for whom survival was a much greater clinical consideration than recovery of kidney function, the authors pointed out. [Kidney Int Suppl 2012;2:1-138; Am J Kidney Dis 2013;61:649-672]

“Unlike patients with kidney failure, there is the potential for some hospitalized patients with AKI to recover enough kidney function to come off dialysis, which is a very important clinical and patient-centred outcome. In this clinical trial, we tested an approach to managing dialysis that increased the likelihood of these patients coming off dialysis—the first intervention ever demonstrated to have such a beneficial effect,” said senior author Dr Chi-yuan Hsu from the University of California San Francisco (UCSF), San Francisco, California, US, in a press statement.

LIBERATE-D population

Liberate-D included 220 adults (mean age 56 years, 67 percent male, 60 percent White) with AKI-D who had a baseline eGFR >15 mL/min/1.73 m², had already initiated kidney replacement therapy (KRT), and were haemodynamically stable. Mean baseline eGFR was 64.8 mL/min/1.73 m², and KRT had been initiated a median of 9 days before randomization. None of the patients were receiving vasopressors, and none required mechanical ventilation via endotracheal tube at enrolment.

The patients were randomly assigned to receive dialysis via a conservative strategy (n=110) or a conventional strategy (n=110). In the conservative strategy group, dialysis was administered only when the following criteria were met: serum urea nitrogen level >112 mg/dL, hyperkalaemia >6 mmol/L (or 5.5 mmol/L despite medical treatment), or arterial blood gas pH <7.15 from pure metabolic acidosis. In the conventional group, dialysis was administered 3 times per week until one of the following urine output or creatinine clearance criteria were met: timed creatinine clearance ≥8 mL/min; 24-h urine output of 1 L/d without diuretics or 2 L/d with diuretics; or spontaneous decrease in creatinine level of >0.3 mg/dL during 12 h.

“Our next steps will be to continue to test and refine this intervention in more patients and additional settings,” said first author Dr Kathleen Liu from UCSF.

Sensible dialysis discontinuation

“LIBERATE-D may arguably be considered a trial of sensible discontinuation vs unnecessary continuation rather than conservative vs conventional dialysis strategies,” wrote Dr Sushrut Waikar from Boston University Chobanian & Avedisian School of Medicine in Boston, Massachusetts, US, in a linked editorial piece. [JAMA 2025;doi:10.1001/jama.2025.21618]

Waikar noted that the criteria for discontinuing dialysis in the conventional strategy group may have been “too strict” and “may not resemble clinical practice.” In this regard, it is notable that the rates of time to first kidney function recovery before hospital discharge diverged between the two groups immediately on randomization after day 0, with around 35 percent of patients in the conservative group vs only <10 percent of patients in the conventional group achieving kidney function recovery and not needing a single subsequent dialysis session.

“The trial results should change clinical practice by emphasizing that KRT with haemodialysis, although life-saving, is nephrotoxic. Each dialysis session exposes litres upon litres of blood to plastic tubing, an artificial membrane, and rapid solute/volume fluxes that do not resemble anything in normal human physiology,” according to Waikar.

“The LIBERATE-D trial patients were far less sick than many of the patients in the ICU who receive KRT, many of whom may in fact need frequent and intensive KRT for optimal management of volume and metabolic needs. But for haemodynamically stable patients with hope for kidney recovery, excessive haemodialysis can set recovery back many days,” he said.