Renal Function after Off- or On-Pump CABG: CORONARY Trial is next #NephJC

The next Nephrology online journal club (#NephJC) will discuss the results of the CORONARY Trial, presented at the late breaking session at the ASN and published this year in JAMA. The trial compared patients undergoing their first coronary artery bypass graft (CABG) surgery using an off- or on-pump technique. The main study published previously revealed no difference with respect to the composite outcome of 30-day mortality, myocardial infarction, stroke or acute kidney injury (AKI) requiring dialysis. The renal function trial was a prespecified substudy involving 2975 (of a total 4752) consecutive patients enrolled in CORONARY with baseline and post-operative serum creatinine data. The renal substudy patients had similar characteristics to the overall CORONARY population.

Outcomes of Interest:

• Post-operative AKI was defined as a 50% increase in the serum creatinine concentration within 30 days of surgery (highest creatinine within 30 days was used).
• Loss of renal function at 1 year = 20% loss in eGFR (using CKD-EPI).

Patients:

• Worldwide enrolment with 42% from Asia and the remainder mostly from Europe (21%) and the Americas (<1% were African American).
• Baseline characteristics of note were a mean age of 68 years, BMI 27, >80% male, almost half were diabetic and a similar number of ‘urgent’ cases between the groups.
• Almost a quarter had CKD (eGFR <60mls/min) and the mean eGFR was 74-75mls/min in the 2 groups.

Results:

• There were 561 AKI events (median time of 2 days post-op to peak creatinine) with a reduced rate with off-pump (17.5%) V. on-pump (20.8%) surgery (adjusted RR 0.83 [CI 0.72-0.97]; p = 0.01).
• Mean eGFR at 1 year was 72 mL/min with off-pump and 73 mL/min with on-pump.
• No significant difference in loss of eGFR at 1 year between off-pump (17.1%) V. on-pump (15.3%) surgery (P = 0.23).
• Those with CKD derived a greater benefit in reduced AKI with off-pump surgery but eGFR loss at 1 year remained insignificant.
• Over 200 patients crossed over between the groups (evenly split) and results of the intention to treat were similar to as-treated analysis.
• Multiple alternative definitions of AKI & loss of kidney function did not alter the main results.

Discussion:

Dialysis requiring AKI has detrimental effects on long-term kidney function. Less severe AKI is more common with major cardiac surgery (only just >1% had AKI requiring dialysis in the original CORONARY trial). It is less clear what effect these more subtle derangements have on long-term function. This study suggests that these ‘mild’ AKI events may not have much longer-term significance, contrary to observational studies [ref, ref]. As pointed out by the authors, this finding has implications for other interventions in mild AKI such as for contrast nephropathy. Does preventing a subtle GFR dip in this scenario have a long-term benefit? The study is limited somewhat by the unique situation studied in the trial (although cardiac surgery provides a very ‘convenient’ insult in which to study AKI). Also, we are relying on serum creatinine and all its limitation to assess kidney function. Moreover, not all eligible patients had creatinine values measured and single measurements and imputed values were often used for the analysis.

Verdict:

This study provides good evidence that off-pump CABG decreases the rate of non-severe AKI but that this does not appear to translate into better renal function at 1 year. When I first heard the results of this study at the ASN (a somewhat deflating session along with lots of other negative/inconclusive Nephrology studies), I was disappointed with the small magnitude of the AKI decrease with off-pump surgery. I had expected the toxic milieu associated with on-pump surgery (aortic cross clamping, exposure to bypass circuit, changes in blood pulsatility) to be associated with much higher rates of AKI, compared to off-pump. The study also questions my preheld assumption that acute drops in GFR, from mild to severe, had a continuous magnitude of impact on long term renal function.

Feel free to get involved by joining the live Twitter chat on Tuesday 26^th August at 9pm Eastern using #NephJC. Also, check out www.nephjc.com for more background and past journal clubs.