Deferring dialysis for AKI improved renal recovery (LIBERATE-D trial)
More evidence for slow-walking dialysis for renal failure in the hospital
Acute kidney injury is a common occurrence during critical illness. Most patients experience mild to moderate AKI and recover most or all of their renal function within weeks.
A sizeable minority develop severe renal failure requiring dialysis, which is often a bad sign. In multiple clinical trials, among patients starting dialysis for AKI in the ICU, more than 40% had died within 90 days.
Initiating dialysis early has intuitive appeal—removing toxins, improving acidosis, etc. Clinical practice guidelines from 2012 advise that patients with dialysis-dependent AKI should receive hemodialysis three times weekly, targeted to reduce urea by two-thirds each session.
However, increasing evidence suggests that systematically delaying renal replacement therapy results in many patients avoiding the need for dialysis altogether.
A new multicenter randomized trial suggests that for new, severe AKI, a conservative RRT strategy—providing dialysis in response to predefined criteria, rather than on a regular schedule—could result in faster recovery of renal function.
The LIBERATE-D Trial
At four U.S. sites (UCSF, Vanderbilt, Wash U, and Intermountain), 220 adults who had already started renal replacement for AKI were randomized to receive dialysis on a scheduled basis three times per week (controls), or as needed according to prespecified metabolic or clinical criteria:
serum urea nitrogen level greater than 112 mg/dL;
hyperkalemia >6 mmol/L (or >5.5 mmol/L after medical treatment);
metabolic acidosis with pH < 7.15 on ABG (or bicarbonate level <12 mEq/L);
acute pulmonary edema attributed to fluid overload, with hypoxemia;
anuria with increasing oxygen requirements attributed to pulmonary edema;
clinician judgment.
The enrolled patients were not critically ill, as a group. Patients who were significantly hypoxemic or mechanically ventilated were excluded, as were those receiving vasopressors.
The primary outcome was renal recovery, defined as not needing dialysis for ≥14 days.
“Dialysis” could include hemodialysis, continuous renal replacement, and/or ultrafiltration.
Restricting Dialysis Improved Renal Recovery
In the restricted-dialysis group, 64% had recovered kidney function at hospital discharge, compared with 50% in the thrice-weekly control group. This translated to a “number needed to not treat” (i.e., restrict dialysis) of 8 to produce one additional patient without ongoing dialysis needs.
Patients in the conservative dialysis arm also recovered renal function faster: within 2 days in the majority of patients, compared to 8.5 days in the scheduled dialysis group.
In fact, they quite frequently were able to forgo dialysis entirely after randomization. Almost all patients in the scheduled-dialysis arm (92%) received dialysis, vs. 66% of those in the conservative arm.
At 90 days, the benefits of greater renal recovery peristed, with only one-third of the conservatively managed patients requiring ongoing dialysis, compared to 42% of the regularly-dialyzed (still a “number needed to not treat” of 8).
A Noisy Mortality Signal
Mortality at 28 days was twice as high in the restricted-dialysis group (12.7% vs 6.4%, non-significant), but at 90 days, it was numerically lower (14.7% vs. 18.5%).
Adverse events
The unblinded authors adjudicated one severe adverse event attributable to study participation in the limited-dialysis group, but they don’t say what it was (with severe events ranging from hyperphosphatemia to cardiac arrest).
Patients in the restricted dialysis group had more fluid removed by ultrafiltration per session, but still had less dialysis-associated hypotension compared to the scheduled dialysis group (69 vs 97 events).
Discussion
Recent randomized trials have suggested that delaying renal replacement in critically ill patients until it is strongly indicated permits many of them to forgo the need for dialysis entirely. AKIKI, IDEAL-ICU, and STARRT-AKI all found no benefit of an early RRT strategy.
In these trials, delaying RRT allowed ~40% of patients to recover sufficiently that they did not require dialysis in the ICU at all, while also avoiding the infectious and mechanical risks of central venous catheterization.
Earlier initiation of RRT in those trials did not clearly improve long-term renal function; on the contrary, in at least one RCT (STARRT-AKI), those randomized to early RRT had an increased need for ongoing dialysis at 90 days, compared to the delayed strategy.
(That said, delaying dialysis or CRRT too long also carries risks. In the AKIKI-2 trial, patients randomized to delaying RRT until BUN increased >140 mg/dL or oliguria was prolonged >72 hours experienced increased 60-day mortality.)
The LIBERATE-D trial adds further support to a conservative approach to dialysis in acute illness, suggesting that limiting dialysis can hasten the recovery of native kidney function.
It’s hypothesized that over-frequent dialysis might worsen kidney injury, through repetitive ischemia (such as during episodes of relative or frank hypotension) or by immune- and inflammatory-mediated mechanisms as blood transits the artificial surfaces of the extracorporeal circuit.
Even if no dialysis-induced injury occurs, frequent dialysis obscures the return of normal kidney function, introducing an inherent delay in the recognition of recovery.
Patients in LIBERATE-D were highly selected—not severely hypoxemic, on mechanical ventilation or vasopressors at enrollment. This might limit its extrapolability, but also opens the door for future trials in more severely ill patients.
Although unblinded, moderate-sized, and enrolling a not-that-critically-ill population, LIBERATE-D aligns with multiple randomized trials suggesting that a conservative approach is reasonable and safe for patients not requiring immediate dialysis in the ICU.
References
KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury
Bagshaw SM et al . Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. The New England Journal of Medicine. 2020;383(3):240-251. doi:10.1056/NEJMoa2000741.
Gaudry S, Hajage D, Martin-Lefevre L, et al. Comparison of Two Delayed Strategies for Renal Replacement Therapy Initiation for Severe Acute Kidney Injury (AKIKI 2): A Multicentre, Open-Label, Randomised, Controlled Trial. Lancet. 2021;397(10281):1293-1300. doi:10.1016/S0140-6736(21)00350-0.
Fayad AI et al. Timing of Kidney Replacement Therapy Initiation for Acute Kidney Injury. The Cochrane Database of Systematic Reviews. 2022;11:CD010612. doi:10.1002/14651858.CD010612.pub3.
Gaudry S, Hajage D, Benichou N, et al. Delayed Versus Early Initiation of Renal Replacement Therapy for Severe Acute Kidney Injury: A Systematic Review and Individual Patient Data Meta-Analysis of Randomised Clinical Trials. Lancet. 2020;395(10235):1506-1515. doi:10.1016/S0140-6736(20)30531-6.
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Uhlig et al. 2012 Clinical Practice Guideline for Acute Kidney Injury. Kidney Disease: Improving Global Outcomes
Coppola S, Chiumello D, Adnan A, et al. Diuretics in critically ill patients: a narrative review of their mechanisms and applications. British Journal of Anaesthesia. 2025;134(6):1638-1647.
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I won’t start CRRT on a dialysis naive patient, in general, without a diuretic challenge. I define a diuretic challenge as two doses of a bumex during resuscitation if they aren’t meeting urine output goals. Employing diuretics early (after adequate resuscitation) can help avoid CRRT and decrease cardiorenal congestion. If it is impossible to spark urine output enough I will use a gtt or start crrt if there is rapidly worsen uncompensated metabolic acidosis.
I think intensivists running crrt, to balance ultrafiltration, Qb, and hemodynamic stability- is important. These things are dynamic and nephrologists aren’t at the bedside. I think CRRT training and credentials for PCCMs is really important and we are undertrained in it.