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Proenkephalin A 119–159 May Predict Post-operative Acute Kidney Injury and in Hospital Mortality Following Open or Endovascular Thoraco-abdominal Aortic Repair

Open ArchivePublished:July 10, 2020DOI:https://doi.org/10.1016/j.ejvs.2020.05.020
      Complex aortic surgery such as thoraco-abdominal aortic aneurysm (TAAA) repair may be associated with an increased risk of complications such as acute kidney injury (AKI) and in hospital mortality.
      • Riambau V.
      • Bockler D.
      • Brunkwall J.
      • Cao P.
      • Chiesa R.
      • Coppi G.
      • et al.
      Editor's choice - management of descending thoracic aorta diseases: clinical practice guidelines of the European society for vascular surgery (ESVS).
      Detection of kidney failure is based on urine volume and serum creatinine levels; however, serum creatinine measurement cannot be made at an early stage thereby delaying detection of AKI, and it can also be associated with several non-renal clinical variables, meaning creatinine is not an ideal predictor of AKI.
      • Waikar S.S.
      • Bonventre J.V.
      Creatinine kinetics and the definition of acute kidney injury.
      Hence, a predictive biomarker of AKI after TAAA repair would be useful in facilitating early therapeutic intervention.
      Enkephalins are endogenous opioids related to numerous physiological functions such as cardiovascular regulation, analgesia, natriuresis, and diuresis. Enkephalin and its receptors are highly expressed in renal tissue, suggesting that enkephalin may play an important biological function in renal physiology. Proenkephalin A 119–159 (penKid) has been described as a promising biomarker associated with AKI after surgery.
      • Shah K.S.
      • Taub P.
      • Patel M.
      • Rehfeldt M.
      • Struck J.
      • Clopton P.
      • et al.
      Proenkephalin predicts acute kidney injury in cardiac surgery patients.
      The present study describes an observational trial to investigate the potential of penKid as a marker of AKI within 48 h of surgery or in hospital mortality in 33 patients undergoing elective open or endovascular TAAA repair in 2017. Patients were included if an elective open or endovascular TAAA repair was planned. TAAA was defined according to the Crawford classification. Exclusion criteria were emergency procedures, age under 18 years, pregnancy, chronic kidney disease requiring permanent dialysis treatment, and ongoing immunosuppressive medication.
      During the study, blood samples were collected before surgery, after admission to the intensive care unit (ICU), and 12, 24, 48, and 72 h after admission to ICU. Plasma was stored at −80 °C.
      AKI within 48 h of surgery was defined according to the Kidney Disease Improving Global Outcomes criteria based on serum creatinine levels.
      • Lamb E.J.
      • Levey A.S.
      • Stevens P.E.
      The Kidney Disease Improving Global Outcomes (KDIGO) guideline update for chronic kidney disease: evolution not revolution.
      Plasma levels of penKid were measured retrospectively using a commercially available chemiluminescence immunoassay (sphingotest® penKid®, SphingoTec GmbH, Hennigsdorf, Germany).
      Statistical analysis included receiver operating characteristic (ROC) curves, which were constructed to assess the sensitivity and specificity of penKid concentration obtained at each time point and to compare its ability to predict AKI within 48 h of surgery or in hospital mortality. PenKid was not normally distributed and was therefore log transformed. Logistic regression was used to derive significance and the area under the ROC curve (AUC) was given as a measure of effect size.
      Mean patient age was 63 (±16.2) years, and 16 patients (48.5%) were women. Endovascular TAAA repair was conducted in 19 patients (57.6%) and open repair in 14 (42.4%). The endovascular repair group was significantly older (75.5 ± 7.1 vs. 50.1 ± 16.4 years, p < .001), connective tissue disease was more common in the open repair group (35.7% vs. 0%, p = .010), and chronic obstructive pulmonary disease was more common in the endovascular repair group (57.9%, vs. 14.3%, p = .019).
      Post-operative AKI was detected in 17 patients (51.5%), and six patients died in hospital after surgery (18.2%). Patients suffering from AKI within 48 h of surgery and those patients who died in hospital showed a partially significant increase of peri-operative penKid during the post-operative measurements (Fig. 1). The course of penKid following endovascular and open TAAA repair was similar.
      Figure 1
      Figure 1Peri-operative levels of Proenkephalin A 119–159 (penKid) before (pre), on admission (adm) for, and 24, 48 and 72 h after elective open or endovascular thoraco-abdominal aortic aneurysm repair in patients presenting with acute kidney injury (AKI) or not (no AKI) within 48 h of surgery.
      PenKid showed a significant correlation with AKI within 48 h of surgery, with an AUC of 0.752 (p = .004) at 12 h and 0.714 (p = .021) at 48 h after admission to the ICU. The most accurate diagnostic abilities of penKid were observed for AKI within 48 h of surgery in the subgroup of patients after open TAAA repair (admission to ICU: AUC 0.750 [p = .078], 24 h: AUC 1.000 [p < .001], 48 h: AUC 0.972 [p < .001]).
      While assessing a correlation between penKid and in hospital mortality, the AUC was 0.827 (p = .002) at 12 h after admission to the ICU, reached 0.877 (p = .005) 48 h and 0.920 (p = .007) 72 h after admission to the ICU.
      This observational pilot study including patients undergoing open or endovascular TAAA repair showed AKI to be the most common complication after surgery, which could possibly be monitored within 72 h of surgery using penKid plasma levels. In addition, increased penKid plasma levels were related to in hospital mortality. Although a distinct separation between patients suffering from AKI and those patients who died was not possible in this retrospective small cohort, the present findings may highlight the role of penKid as a potential biomarker for prediction of post-operative AKI and in hospital mortality.
      Prediction of an adverse outcome after complex aortic surgery is difficult, but of clinical relevance. As yet, the guidelines of the European Society of Vascular Surgery do not give a clear recommendation for the use of any new biomarker focusing on AKI; however, biomarkers for risk assessment and outcome prediction would be a desirable tool for adequate initiation of treatment bundles leading to improved patient outcome.
      • Riambau V.
      • Bockler D.
      • Brunkwall J.
      • Cao P.
      • Chiesa R.
      • Coppi G.
      • et al.
      Editor's choice - management of descending thoracic aorta diseases: clinical practice guidelines of the European society for vascular surgery (ESVS).
      ,
      • Wanhainen A.
      • Verzini F.
      • Van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      Editor's choice - European society for vascular surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      Although the results of this study are promising, the hypothesis generating character of the study must be emphasised. For validation, further larger and multicentre clinical studies are required to verify the clinical relevance of penKid as a biomarker for early detection of AKI and early mortality after open or endovascular TAAA surgery.

      References

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        • Brunkwall J.
        • Cao P.
        • Chiesa R.
        • Coppi G.
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        Proenkephalin predicts acute kidney injury in cardiac surgery patients.
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        The Kidney Disease Improving Global Outcomes (KDIGO) guideline update for chronic kidney disease: evolution not revolution.
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        • Wanhainen A.
        • Verzini F.
        • Van Herzeele I.
        • Allaire E.
        • Bown M.
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        • et al.
        Editor's choice - European society for vascular surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
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