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Biomarker Proenkephalin Investigated in Diagnosis of Acute Kidney Injury

By LabMedica International staff writers
Posted on 12 May 2022
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Image: ROC curve AUC and levels of Proenkephalin A 119–159 (PENK) 48 hours after liver transplantation in the need-renal replacement therapy groups (Photo courtesy of University of Sao Paulo)
Image: ROC curve AUC and levels of Proenkephalin A 119–159 (PENK) 48 hours after liver transplantation in the need-renal replacement therapy groups (Photo courtesy of University of Sao Paulo)

Liver transplantation (LT) is the only treatment available for patients with end-stage liver disease, such as liver cancer or acute and subacute liver failure. Among the various types of postoperative organ damage, acute kidney injury (AKI) is particularly prevalent, developing in 5% to 20% of patients undergoing major non-cardiac surgery.

Proenkephalin A 119–159 (PENK) was recently described to be a reliable biomarker (BM) of renal function, with a long half-life in vivo, stability after collection, and levels that are not influenced by age or sex. In addition, it is not a plasma-bound protein and, therefore, is exclusively filtered in the glomerulus, making it a promising BM for the analysis of renal function in critically ill patients.

Nephrologists at the University of Sao Paulo (Sao Paulo, Brazil) and their colleagues selected 57 patients undergoing LT to include for analysis. They selected the most severe patients for analysis with KDIGO 3 and the need for renal replacement therapy (RRT) versus KDIGO 0 and 1. Of the 57 patients undergoing LT, 50 (88%) developed acute kidney injury (AKI) and were categorized as follows: no-AKI/mild-AKI 21 (36.8%) and severe-AKI 36 (63.2%).

Blood samples were collected from central venous catheters or arterial lines, and urine was collected through indwelling catheters. The team used the penKid immunoassay kit (PEK96, SphingoTec GmbH, Hennigsdorf, Germany) that measures plasma Proenkephalin119-159, a stable surrogate for the kidney stimulating hormone enkephalin, by immunoluminometric assay in pmol/L. The biomarker cystatin C was measured in urine and plasma using a kit (BioLegend, San Diego, CA, USA). Serum creatinine was measured by the Roche automatic kinetic method and the Cobas c720 analyzer (Roche Diagnostics, Rotkreuz, Switzerland) were used.

The investigators reported that during the preoperative period, only PENK was significantly higher in patients with severe AKI, with an AUC of 0.69, a cutoff of 55.3 pmol/L, a sensitivity of 0.86, a specificity of 0.52, and an accuracy of 0.75. In addition, subclinical AKI was determined preoperatively in 32 patients. Forty-eight hours after LT, PENK maintained its performance in determining severe AKI, with an AUC of 0.83, a cutoff of 119.1 pmol/L, a sensitivity of 0.81, a specificity of 0.90, and an accuracy of 0.84. PENK detected AKI 48 hours earlier than serum creatinine. In a multivariate linear regression analysis, PENK was an independent predictor of severe AKI. Forty-eight hours after LT, the serum creatinine levels were approximately two times higher in patients with severe AKI.

The authors concluded that the filtration biomarker PENK was shown to be promising, with greater accuracy and more precocity for severe AKI, including the preoperative period. Although serum creatinine is a later marker, simultaneously combining functional markers with those of damage to the kidneys (serum creatinine) may help in the management and prevention of AKI progression. The study was published on May 6, 2022 in the journal Practical Laboratory Medicine.

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University of Sao Paulo
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