Early renal replacement therapy improves survival in acute liver failure, cerebral edema

Key takeaways:

• Mortality at 28 days was lower in patients who received continuous renal replacement therapy within 12 hours of therapeutic plasma exchange.
• Mean arterial pressure and arterial lactate also improved.

SAN DIEGO — Preemptive continuous renal replacement therapy after therapeutic plasma exchange reduced mortality and improved other outcomes in patients with acute liver failure and cerebral edema, according to data from The Liver Meeting.

“In this part of the world, live-donor liver transplantation is the more active transplant program; however, it is not available because of the lack of donors,” Rakhi Maiwall, MD, DM, professor of hepatology at the Institute of Liver and Biliary Sciences in New Delhi, told Healio. “Therefore, liver support therapies provide an effective bridge to support the failing liver.”

Two extracorporeal liver support therapies — therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) — have the potential to “tide the cytokine storm,” Maiwall said, and improve transplant-free survival in patients with ALF.

With data lacking on outcomes associated with early initiation of CCRT after TPE, Maiwall and colleagues conducted a randomized controlled trial of 86 patients (aged 30.6 years) with ALF and cerebral edema, all of whom underwent TPE via centrifugal apheresis following initial resuscitation. Patients in group 1 (n = 44) received CRRT within the first 12 hours of TPE, while those in group 2 (n = 42) started CRRT after worsening hyperammonemia or upon meeting renal indications.

The primary outcome was 28-day mortality, and secondary endpoints included improvement in ammonia, mean arterial pressure and arterial lactate.

According to study results, 47% of patients died at 28 days and 8% underwent live-donor LT. Although there was no difference between groups 1 and 2 in mortality in intention-to-treat analysis (48% vs. 45%; HR = 0.89; 95% CI, 0.48-1.65), per-protocol analysis demonstrated significantly reduced mortality among patients in group 1 (46.2% vs. 75%; HR = 0.37; 95% CI, 0.19-0.74).

In addition, patients in group 1 experienced improvements in mean arterial pressure (P = .003), arterial lactate (P = .04), ammonia (P = .009) and Sequential Organ Failure Assessment score (P = .04) on day 3.

“CRRT with therapeutic plasma exchange is synergistic in improving outcomes in ALF with cerebral edema,” Maiwall said, adding that biomarkers for identification of those with spontaneous recovery are needed.

The researchers also reported that each 1-hour delay in CRRT was associated with higher mortality (HR = 1.03; 95% CI, 1.02-1.04).

“We propose an early initiation of CRRT to TPE in patients with ALF who have cerebral edema,” Maiwall said. “TPE, even though it ameliorates cytokine storm, is ineffective in ammonia reduction and therefore, combination may be better compared to either strategy alone.”

However, she added, “it is still not known whether CRRT alone is as effective as TPE combined with CRRT in improving outcomes of ALF patients.”