Acute Kidney Injury Implicated in Multiple Organ Failure

CHICAGO – Early kidney failure was associated with a 19-fold increased risk of multiple organ failure and a sixfold higher risk of death in a retrospective analysis of 1,273 trauma cases.

The study was done at the Rocky Mountain Regional Trauma Center of the University of Colorado at Denver to learn more about the epidemiology of acute kidney injury and its role in acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF).

"Of the four major organ systems involved, the kidneys are often overlooked as MOF development has been thought to occur sequentially, being initiated by the lungs," Dr. Max V. Wohlauer said at the annual meeting of the American Association for the Surgery of Trauma.

He noted that postinjury MOF death rates remain high at 60%, "despite widespread availability [of] renal replacement therapy," and that therefore the prevention of early acute kidney injury could help to reduce complications and death rates in the critically ill.

Conceptually, MOF occurs as patients are resuscitated into a state of early systemic hyperinflammation, explained Dr. Wohlauer, who is now at the University of Washington Medical Center, Seattle. Although a mild response may be beneficial and will resolve in most patients as they recover, a massive traumatic insult can overwhelm a patient’s response to resuscitation, precipitating early organ failure.

"As neutrophil mediated ischemia-reperfusion injury is thought to be the driving factor in the development of ARDS, recent investigation highlights the critical function of the neutrophils in acute kidney injury as well," Dr. Wohlauer said. "Indeed, emerging evidence indicates that there is a direct contribution of the inflamed, injured kidney in the development of ARDS and MOF. Recent research has shown that acute kidney injury leads to increased vascular permeability and both cellular and soluble inflammation in the lungs, and that acute kidney injury–mediated lung dysfunction begins within hours."

Of the 1,273 patients the study evaluated, 21% went on to develop MOF with an overall mortality of 8%. Early acute kidney injury was detected in only 2% of the patients, but was associated with a 78% MOF rate and a 27% death rate, higher rates than isolated cardiac, liver, or lung dysfunction, Dr. Wohlauer reported. (See box.) The study defined acute kidney injury as an acute increase in creatinine greater than 1.8 mg/dL. Renal replacement therapy was mostly ineffective in these patients, he said.

The most important independent predictors of early acute kidney failure were shock, day 1 crystalloid count, day 2 base deficit, and a need for blood transfusion in the first 12 hours, according to Dr. Wohlauer. "Most patients who developed early kidney injury culminated in full-blown MOF, whereas only 34% of the lung failure cases evolved to ... full MOF," he said.

Dr. Mitchell Jay Cohen of San Francisco General Hospital noted that no consensus exists in the hospital on the definition of acute kidney injury, and that nephrology uses different definitions. "Can you identify a group of patients with acute kidney failure [who] don’t go on to develop multiple organ failure, and what distinguishes these two groups?"

Dr. Wohlauer noted that the renal component of the Denver Postinjury MOF Scale score (creatinine greater than 1.8 mg/dL) correlated strongly with the development of MOF, but that patients with acute kidney injury using the RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) criteria did not go on to develop subsequent MOF.

"We’re suggesting that a creatinine of 1.8 is a severe insult to the kidney, and by the time that occurs [on day 2], a lot of the injury and inflammation has already occurred and we’re pedaling backwards to catch up," he said.

"When it comes to postinjury acute kidney injury, an ounce of prevention is worth a pound of cure," Dr. Wohlauer said. He noted that conservative strategies, including judicious use of IV contrast and rational use of hypotensive resuscitation, may help prevent early acute kidney injury and ensuing MOF.

"Once acute kidney injury had reared its ugly head, renal replacement therapy did very little to alter the progression of disease," he said.

Dr. Wohlauer said he had no conflicts to disclose. The study received funding from the National Institutes of Health.

CHICAGO – Early kidney failure was associated with a 19-fold increased risk of multiple organ failure and a sixfold higher risk of death in a retrospective analysis of 1,273 trauma cases.

The study was done at the Rocky Mountain Regional Trauma Center of the University of Colorado at Denver to learn more about the epidemiology of acute kidney injury and its role in acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF).

"Of the four major organ systems involved, the kidneys are often overlooked as MOF development has been thought to occur sequentially, being initiated by the lungs," Dr. Max V. Wohlauer said at the annual meeting of the American Association for the Surgery of Trauma.

He noted that postinjury MOF death rates remain high at 60%, "despite widespread availability [of] renal replacement therapy," and that therefore the prevention of early acute kidney injury could help to reduce complications and death rates in the critically ill.

Conceptually, MOF occurs as patients are resuscitated into a state of early systemic hyperinflammation, explained Dr. Wohlauer, who is now at the University of Washington Medical Center, Seattle. Although a mild response may be beneficial and will resolve in most patients as they recover, a massive traumatic insult can overwhelm a patient’s response to resuscitation, precipitating early organ failure.

"As neutrophil mediated ischemia-reperfusion injury is thought to be the driving factor in the development of ARDS, recent investigation highlights the critical function of the neutrophils in acute kidney injury as well," Dr. Wohlauer said. "Indeed, emerging evidence indicates that there is a direct contribution of the inflamed, injured kidney in the development of ARDS and MOF. Recent research has shown that acute kidney injury leads to increased vascular permeability and both cellular and soluble inflammation in the lungs, and that acute kidney injury–mediated lung dysfunction begins within hours."

Of the 1,273 patients the study evaluated, 21% went on to develop MOF with an overall mortality of 8%. Early acute kidney injury was detected in only 2% of the patients, but was associated with a 78% MOF rate and a 27% death rate, higher rates than isolated cardiac, liver, or lung dysfunction, Dr. Wohlauer reported. (See box.) The study defined acute kidney injury as an acute increase in creatinine greater than 1.8 mg/dL. Renal replacement therapy was mostly ineffective in these patients, he said.

The most important independent predictors of early acute kidney failure were shock, day 1 crystalloid count, day 2 base deficit, and a need for blood transfusion in the first 12 hours, according to Dr. Wohlauer. "Most patients who developed early kidney injury culminated in full-blown MOF, whereas only 34% of the lung failure cases evolved to ... full MOF," he said.

Dr. Mitchell Jay Cohen of San Francisco General Hospital noted that no consensus exists in the hospital on the definition of acute kidney injury, and that nephrology uses different definitions. "Can you identify a group of patients with acute kidney failure [who] don’t go on to develop multiple organ failure, and what distinguishes these two groups?"

Dr. Wohlauer noted that the renal component of the Denver Postinjury MOF Scale score (creatinine greater than 1.8 mg/dL) correlated strongly with the development of MOF, but that patients with acute kidney injury using the RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) criteria did not go on to develop subsequent MOF.

"We’re suggesting that a creatinine of 1.8 is a severe insult to the kidney, and by the time that occurs [on day 2], a lot of the injury and inflammation has already occurred and we’re pedaling backwards to catch up," he said.

"When it comes to postinjury acute kidney injury, an ounce of prevention is worth a pound of cure," Dr. Wohlauer said. He noted that conservative strategies, including judicious use of IV contrast and rational use of hypotensive resuscitation, may help prevent early acute kidney injury and ensuing MOF.

"Once acute kidney injury had reared its ugly head, renal replacement therapy did very little to alter the progression of disease," he said.

Dr. Wohlauer said he had no conflicts to disclose. The study received funding from the National Institutes of Health.

CHICAGO – Early kidney failure was associated with a 19-fold increased risk of multiple organ failure and a sixfold higher risk of death in a retrospective analysis of 1,273 trauma cases.

The study was done at the Rocky Mountain Regional Trauma Center of the University of Colorado at Denver to learn more about the epidemiology of acute kidney injury and its role in acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF).

"Of the four major organ systems involved, the kidneys are often overlooked as MOF development has been thought to occur sequentially, being initiated by the lungs," Dr. Max V. Wohlauer said at the annual meeting of the American Association for the Surgery of Trauma.

He noted that postinjury MOF death rates remain high at 60%, "despite widespread availability [of] renal replacement therapy," and that therefore the prevention of early acute kidney injury could help to reduce complications and death rates in the critically ill.

Conceptually, MOF occurs as patients are resuscitated into a state of early systemic hyperinflammation, explained Dr. Wohlauer, who is now at the University of Washington Medical Center, Seattle. Although a mild response may be beneficial and will resolve in most patients as they recover, a massive traumatic insult can overwhelm a patient’s response to resuscitation, precipitating early organ failure.

"As neutrophil mediated ischemia-reperfusion injury is thought to be the driving factor in the development of ARDS, recent investigation highlights the critical function of the neutrophils in acute kidney injury as well," Dr. Wohlauer said. "Indeed, emerging evidence indicates that there is a direct contribution of the inflamed, injured kidney in the development of ARDS and MOF. Recent research has shown that acute kidney injury leads to increased vascular permeability and both cellular and soluble inflammation in the lungs, and that acute kidney injury–mediated lung dysfunction begins within hours."

Of the 1,273 patients the study evaluated, 21% went on to develop MOF with an overall mortality of 8%. Early acute kidney injury was detected in only 2% of the patients, but was associated with a 78% MOF rate and a 27% death rate, higher rates than isolated cardiac, liver, or lung dysfunction, Dr. Wohlauer reported. (See box.) The study defined acute kidney injury as an acute increase in creatinine greater than 1.8 mg/dL. Renal replacement therapy was mostly ineffective in these patients, he said.

The most important independent predictors of early acute kidney failure were shock, day 1 crystalloid count, day 2 base deficit, and a need for blood transfusion in the first 12 hours, according to Dr. Wohlauer. "Most patients who developed early kidney injury culminated in full-blown MOF, whereas only 34% of the lung failure cases evolved to ... full MOF," he said.

Dr. Mitchell Jay Cohen of San Francisco General Hospital noted that no consensus exists in the hospital on the definition of acute kidney injury, and that nephrology uses different definitions. "Can you identify a group of patients with acute kidney failure [who] don’t go on to develop multiple organ failure, and what distinguishes these two groups?"

Dr. Wohlauer noted that the renal component of the Denver Postinjury MOF Scale score (creatinine greater than 1.8 mg/dL) correlated strongly with the development of MOF, but that patients with acute kidney injury using the RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) criteria did not go on to develop subsequent MOF.

"We’re suggesting that a creatinine of 1.8 is a severe insult to the kidney, and by the time that occurs [on day 2], a lot of the injury and inflammation has already occurred and we’re pedaling backwards to catch up," he said.

"When it comes to postinjury acute kidney injury, an ounce of prevention is worth a pound of cure," Dr. Wohlauer said. He noted that conservative strategies, including judicious use of IV contrast and rational use of hypotensive resuscitation, may help prevent early acute kidney injury and ensuing MOF.

"Once acute kidney injury had reared its ugly head, renal replacement therapy did very little to alter the progression of disease," he said.

Dr. Wohlauer said he had no conflicts to disclose. The study received funding from the National Institutes of Health.