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

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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 26th August at 9pm Eastern using #NephJC. Also, check out www.nephjc.com
for more background and past journal clubs.

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