Pam Harrison

May 23, 2016

VIENNA — The initiation of renal replacement therapy less than 8 hours after the onset of stage 2 acute kidney injury significantly reduces all-cause mortality at 90 days, according to results from the ELAIN randomized clinical trial.

In addition, early intervention shortens other clinical end points, such as time spent on dialysis, mechanical ventilation, and overall hospital stay.

"You don't want to dialyze a patient who doesn't need therapy because it is associated with complications, said Alexander Zarbock, MD, from University Hospital Munster in Germany.

However, "when you combine early clinical conditions with the biomarker we used, you can predict which patients will develop severe acute kidney injury," he told Medscape Medical News. With such an approach, "you can initiate renal replacement therapy early. It's better for the patient and it's better for outcomes."

The study was presented here at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 53rd Congress, and published online simultaneously in JAMA.

For their multicenter study, Dr Zarbock and his colleagues randomized 112 patients to early treatment, initiated a median of 6 hours after the onset of stage 2 acute kidney injury, and 119 patients to delayed treatment, initiated a median of 25.5 hours after the onset of stage 2 acute kidney injury.

All patients were critically ill, had no life-threatening complications, had a plasma level of neutrophil gelatinase-associated lipocalin in excess of 150 mg/mL, and met the criteria for stage 2 acute kidney injury, defined by Kidney Disease: Improving Global Outcomes (KDIGO) as a serum creatinine level at least two times greater than baseline or a urinary output of less than 0.5 mL/kg per hour for at least 12 hours.

At 90 days, the mortality rate was lower in the early group than in the delayed group (39.3% vs 54.7%; = .03), and the absolute risk reduction for early treatment was 15.4%. In addition, secondary end points were better in the early group than in the delayed group.

Table. Secondary End Points in the Study Cohort

Outcome Early Treatment Group Delayed Treatment Group P Value
Median time on dialysis, days 9 25 .04
Time spent on mechanical ventilation, hours 125.5 181 .002
Overall length of hospital stay, days 51 82 <.001

 

At 90 days, more patients in the early group than in the delayed group had recovered renal function (53.6% vs 38.7%; = .02). However, there was no difference in the need for dialysis between the two groups the 90 days.

It is interesting that a difference in the initiation of treatment of less than 24 hours can have such significant effects on multiple end points, including 90-day mortality, Glenn Chertow, MD, from Stanford University in Palo Alto, California, and Wolfgang Winkelmayer, MD, from the Baylor College of Medicine in Houston, write in an editorial accompanying the published results.

However, "other single-center, modestly sized published trials of dialytic interventions have yielded similarly remarkable results," the pair point out. For example, one study of 114 patients showed that rates of in-hospital mortality were lower in the group that received hemofiltration filtration than in the group that received a saline infusion (2% vs 14%; P = .02), as were rates of 1-year mortality (10% vs 30%; P = .01) (N Engl J Med. 2003;349:1333-1340).

"At the time, many clinicians thought these results were implausible; to date no confirmatory trials have been conducted," Drs Chertow and Winkelmayer note.

Whether the findings presented by Dr Zarbock are plausible or not, "investigators have performed a rigorous trial and have presented their results, appropriately, with responsible and conservative reporting," the editorialists explain. "In view of the provocative findings reported by Zarbock et al, it is the responsibility of the nephrology and critical care communities to confirm or refute these findings across multiple sites in a much larger, diverse population."

There are conflicting data right now on whether early treatment really does improve outcomes for patients with acute kidney injury, said Denis Fouque, MD, PhD, from the University of Lyon in France, who is chair of the ERA-EDTA paper selection committee.

In a recent multicenter study, mortality differences between early treatment and delayed treatment were not significant (48.5% vs 49.7%) (N Engl J Med. Published online May 15, 2016). However, diuresis, a sign of improved kidney function, occurred earlier in the delayed group (P < .00.1).

"Any treatment brings some risk to the patient, so if you don't start dialysis, you can avoid dialysis-related complications, such as bleeding and catheter-related infection," Dr Fouque explained. "It's really up to an individual doctor's perception of when to start dialysis, but relying only on KDIGO biological numbers may not be sufficient to decide when to initiate treatment."

This study was funded by the Else-Kroner Fresenius Stiftung. Dr Zarbock reports receiving grant support and lecture fees from Astute Medical. Dr Chertow reports serving on the board of directors of Satellite Healthcare, and serving as an advisor or consultant for Akebia, AMAG, Amgen, Ardelyx, Durect, Keryx, Outset Medical, Physiowave, PuraCath, Relypsa, Thrasos, and ZS Pharma. Dr Winkelmayer reports serving as an advisor or consultant for Akebia, AMAG, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Merck, Sharpe & Dohme, Medtronic, Relypsa, Vifor Fresenius Medical Care Renal Pharma, and Zoll.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 53rd Congress: Abstract LB02. Presented May 22, 2015.

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