Initial Kidney Protection of Off-Pump CABG May Not Last

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The immediate protection against acute kidney injury (AKI) offered by off-pump vs on-pump coronary artery bypass graft (CABG) surgery fails to make any difference in long-term kidney function, reports a paper published online June 2, 2014, ahead of print in the Journal of the American Medical Association.

Based on these results, interventions to reduce such early damage may be futile, study author Amit X. Garg, MD, PhD, of London Health Sciences Centre (London, Canada), told TCTMD in a telephone interview.

Michael J. Mack, MD, of Baylor Health Care System (Dallas, TX), however, commented to TCTMD that even if the renal protection offered by off-pump CABG only extends to AKI, the technique is still worth using.

While off-pump CABG reduced the risk of AKI (≥ 50% increase in SCr concentration) within 30 days of surgery, both approaches led to similar loss of kidney function (≥ 20% loss in estimated glomerular filtration rate) at 1 year (table 1).

Table 1. Relationship Between CABG Technique and Kidney Damage

Results were consistent across various definitions of AKI and loss of kidney function as well as when considering both types of kidney damage in combination with death.

Notably, AKI was short lived in most cases; of the patients with AKI who survived their index hospital stay, the most recent available SCr value prior to discharge showed that 72% of the off-pump group and 64% of the on-pump group no longer showed signs of kidney damage.

Patients with baseline chronic kidney disease obtained protection against AKI with off- pump CABG (adjusted RR 0.63; 95% CI 0.46-0.83) while those with normal function did not (adjusted RR 0.98; 95% CI 0.79-1.11; P for interaction = .01). Furthermore, AKI vs no AKI independently predicted greater likelihood of losing kidney function at 1 year (adjusted OR 3.37; 95% CI 2.65-4.28; P < .001).

What if AKI Has No Long-term Fallout?

Rather than having direct implications for practice, Dr. Garg said, “the more important message out of this paper is its impact on how we think about… mild-to-moderate changes in kidney function.”

Many trials are investigating “interventions used to prevent [such changes] and those interventions have costs, and they have side effects,” he commented. “What we’re showing in this study is that while we were able to influence that surrogate outcome… it had no lasting impact on kidney health.”

The finding supports the US Food and Drug Administration’s position that these mild-to-moderate changes cannot serve as an outcome for the purposes of regulatory approval, Dr. Garg added. “There are tons of trials using this is as an outcome, and we see them in the literature all the time. Using this outcome on its own may or may not be in the service of patients.”

Off- and on-pump CABG “are both pretty comparable. In the hands of an experienced surgeon, either is probably fine,” he concluded.

Yet the JAMA paper lists several reasons why the CORONARY substudy may not have observed a connection between short-term injury and long-term function. Among them are:

• Too short a follow-up duration
• Errors in SCr measurements
• Differences in follow-up care between the 2 CABG techniques
• Other nonkidney-related effects of off- vs on-pump CABG
• Too small a magnitude of reduction in AKI affecting too few patients
• The possibility that mild-to-moderate AKI may not lead to chronic kidney disease

The need for proof of benefit “has implications for the development, testing, and use of interventions designed solely to prevent the degrees of acute kidney injury observed in CORONARY, and in determining acceptable adverse effects and costs of such interventions,” the researchers write, citing N-acetylcysteine and intravenous sodium bicarbonate as examples.

Off-Pump CABG Still Worthy, Particularly in Select Patients

In a telephone interview, Dr. Mack said that while the evidence has been mixed, “there is this sense that off-pump CABG may be protective of renal function.”

CORONARY offers “a little bit of a signal” showing that benefit, but given that the study included patients with and without baseline kidney disease, “I’m actually [slightly] surprised that they detected a difference at all,” he commented.

The study’s cutoff for defining baseline disease is an estimated glomerular filtration rate below 60 mL/min/1.73 m². To be more informative, Dr. Mack said, the limit should have been set at 30 mL/min/1.73 m². “Those are the patients that we selectively do off-pump surgery in because those are the patients [for whom] we want to do everything we potentially can to preserve [function].”

Moreover, “[e]ven if it doesn’t affect kidney function at 1 year, acute kidney injury is a significant cause of increased resource utilization, prolonged length of stay, and morbidity in the hospital. Even if it only [reduces] that, that’s good enough for me,” he concluded.

Garg AX, Devereaux PJ, Yusuf S, et al. Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial. JAMA. 2014;Epub ahead of print.

Related Stories:

• Off-Pump CABG May Be Safer in Higher-Risk Patients vs. On-Pump CABG
• CABG Equally Safe in Elderly Patients Whether On- or Off-Pump
• CORONARY Bypass Shows Similar Results Whether On-Pump or Off