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ATLANTA -- Patients who had coronary bypass surgery (CABG) without a bypass machine had a significantly lower risk of acute kidney injury (AKI), but the difference did not translate into a long-term benefit, a randomized trial showed.

Off-pump surgery was associated with a 17% reduction in the relative risk of AKI. A year after surgery, loss of kidney function had occurred in a similar proportion of patients who had surgery with or without a bypass pump.

The results added to findings from an earlier meta-analysis showing a much larger reduction in the risk of AKI in association with off-pump CABG, , of the London Kidney Clinical Research Unit in London, Ont., reported here at the American Society of Nephrology Kidney Week.

"We now have convincing evidence that cardiac surgery done off pump reduces the risk of mild to moderate AKI," Garg said. "The relative and absolute risk reduction appears greatest in patients with chronic kidney disease."

"We need proof to claim an intervention which reduces AKI better preserves long-term kidney function for the group that received it," he said of the lack of association between early and long-term kidney outcomes. "A mild or moderate nonsustained increase in creatinine is a surrogate outcome."

Garg presented findings from a follow-up analysis of the CORONARY randomized trial, whose investigators examined multiple outcomes following CABG performed with or without the aid of a cardiopulmonary bypass pump. Previous reports from the trial showed no difference in the composite outcome of death, nonfatal myocardial infarction, stroke, or need for dialysis,either at or after surgery.

CORONARY investigators continued their analysis of the results by examining the relationship between early and late kidney effects after CABG.

"A cardiopulmonary bypass machine can have many adverse effects on the kidney," Garg said. "We expected off-pump compared to on-pump to reduce the risk of postop AKI. If we were correct, we wanted to know if there was a difference in kidney function between the two groups 1 year later."

CORONARY involved almost 3,000 patients enrolled at 63 sites in 16 countries. They were randomized to undergo CABG with or without the assistance of a bypass pump. Garg said 7% of patients in each group crossed over to the opposite group, but intention-to-treat and per-protocol analyses produced similar results.

Investigators defined postoperative AKI as ≥50% increase in serum creatinine from pre-randomization values. They defined loss of kidney function at 1 year as ≥20% loss in estimated glomerular filtration rate (eGFR) as compared with measures obtained prior to randomization.

The groups exhibited no significant differences in baseline demographic or clinical characteristics, including the use of medications that can affect assessment of kidney function (ACE inhibitors, angiotensin receptor blockers, and diuretics).

Preoperative presence of chronic kidney disease (CKD) was the only prespecified subgroup. Investigators defined CKD as eGFR ≤60 mL/min/1.73 m², and one-fourth of patients in each group had CKD by that definition.

The data showed that the off-pump group had an AKI rate of 17.5% compared with 20.8% in the on-pump group (P=0.01). Using multiple creatinine-based definitions of AKI, investigators consistently found significantly higher rates in the off-pump group (P=0.04 to P=0.001).

A year after surgery, 17.1% of the off-pump group had CKD as compared with 15.3% of the on-pump group, a nonsignificant difference. Once again, Garg and colleagues performed analyses using various definitions of CKD, and none of the differences achieved statistical significance.

The analysis of patients with and without CKD prior to surgery yielded a larger, statistically significant difference in the rate of AKI in favor of off-pump surgery. Among patients with normal kidney function prior to surgery, AKI occurred in 16.9% of the off-pump group and 18% of the on-pump group, which translated into a nonsignificant 7% reduction in the relative risk of AKI. The relative benefit of off-pump surgery increased to 41% in patients who had CKD prior to surgery (19.2% versus 30.2%, P=0.01).

"However, we observed no evidence that reducing the risk of AKI better preserved 1-year kidney function in those with preoperative CKD," Garg said.

The investigators evaluated the relationship between postoperative AKI and reduced kidney function at 1 year, irrespective of treatment assignment. Among patients who had no AKI after surgery, 12.5% had ≥20% loss in eGFR at 1 year as compared with 32.1% of patients who did have postoperative AKI (odds ratio 3.4, 95% CI 2.6-4.3, P<0.001).

The lack of association between early and long-term kidney outcomes came as a surprise to nephrologist , of Duke University.

The study "clearly established that the off-pump procedure is associated with a significantly reduced risk for AKI," Coffman told 番茄社区 in an email. "On the other hand, the reduced incidence of AKI was not associated with any improvement in kidney function long term. This is important and surprising, since a number of previous studies have suggested that transient acute kidney injury is a significant cause of long-term chronic kidney disease."

"A caveat is that the vast majority of AKI events in the the trial were in the mild to moderate range, and would be expected to largely be caused by ischemia," he added. "It therefore remains possible that preventing more severe AKI or AKI from other causes may preserve long-term kidney function."

The findings are consistent with those of other studies that have compared off- and on-pump CABG, said cardiothoracic surgeon , of the University of Pittsburgh.

"This has been a controversial issue for some time," Gleason told 番茄社区. "Some studies have shown that on-pump is equivalent to off-pump, but renal function is one of the things that proponents of off-pump have been touting for some time. This corroborates that viewpoint, and, overall, I think it's a positive study."

Both surgical strategies remain in use and have ardent supporters, he added, noting that he has used off-pump surgery for cardiac revascularization procedures "for years."

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