Off-pump CABG reduces acute kidney injury, but not long-term function loss

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.