Delaying renal replacement therapy in critically ill patients has advantages

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..